Language：English   Publishing type：Research paper (scientific journal)  

Radon inhalation decreases the level of lipid peroxide (LPO); this is attributed to the activation of antioxidative functions. This activation contributes to the beneficial effects of radon therapy, but there are no studies on the risks of radon therapy, such as DNA damage. We evaluated the effect of radon inhalation on DNA damage caused by oxidative stress and explored the underlying mechanisms. Mice were exposed to radon inhalation at concentrations of 2 or 20 kBq/m3 (for one, three, or 10 days). The 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels decreased in the brains of mice that inhaled 20 kBq/m3 radon for three days and in the kidneys of mice that inhaled 2 or 20 kBq/m3 radon for one, three or 10 days. The 8-OHdG levels in the small intestine decreased by approximately 20-40% (2 kBq/m3 for three days or 20 kBq/m3 for one, three or 10 days), but there were no significant differences in the 8-OHdG levels between mice that inhaled a sham treatment and those that inhaled radon. There was no significant change in the levels of 8-oxoguanine DNA glycosylase, which plays an important role in DNA repair. However, the level of Mn-superoxide dismutase (SOD) increased by 15-60% and 15-45% in the small intestine and kidney, respectively, following radon inhalation. These results suggest that Mn-SOD probably plays an important role in the inhibition of oxidative DNA damage.

DOI： 10.1093/jrr/rrab069

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Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)  

DOI： 10.50955/happyokai.1.0_86

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DOI： 10.50955/happyokai.1.0_85

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It is held that the skin dose from radon progeny is not negligibly small and that introducing cancer is a possible consequence under normal circumstances as there are a number of uncertainties in terms of related parameters such as activity concentrations in air and water, target cells in skin, skin covering materials, and deposition velocities. An interesting proposal has emerged in that skin exposure to natural radon-rich thermal water as part of balneotherapy can produce an immune response to induce beneficial health effects. The goal of this study was to obtain generic dose coefficients with a focus on the radon progeny deposited on the skin in air or water in relation to risk or treatment assessments. We thus first estimated the skin deposition velocities of radon progeny in air and thermal water based on data from the latest human studies. Skin dosimetry was then performed under different assumptions regarding alpha-emitting source position and target cell (i.e. basal cells or Langerhans cells). Furthermore, the impact of the radon progeny deposition on effective doses from all exposure pathways relating to 'radon exposure' was assessed using various possible scenarios. It was found that in both exposure media, effective doses from radon progeny inhalation are one to four orders of magnitude higher than those from the other pathways. In addition, absorbed doses on the skin can be the highest among all pathways when the radon activity concentrations in water are two or more orders of magnitude higher than those in air.

DOI： 10.1093/jrr/rrab030

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Radon inhalation activates antioxidative functions in mouse organs, thereby contributing to inhibition of oxidative stress-induced damage. However, the specific redox state of each organ after radon inhalation has not been reported. Therefore, in this study, we evaluated the redox state of various organs in mice following radon inhalation at concentrations of 2 or 20 kBq/m3 for 1, 3 or 10 days. Scatter plots were used to evaluate the relationship between antioxidative function and oxidative stress by principal component analysis (PCA) of data from control mice subjected to sham inhalation. The results of principal component (PC) 1 showed that the liver and kidney had high antioxidant capacity; the results of PC2 showed that the brain, pancreas and stomach had low antioxidant capacities and low lipid peroxide (LPO) content, whereas the lungs, heart, small intestine and large intestine had high LPO content but low antioxidant capacities. Furthermore, using the PCA of each obtained cluster, we observed altered correlation coefficients related to glutathione, hydrogen peroxide and LPO for all groups following radon inhalation. Correlation coefficients related to superoxide dismutase in organs with a low antioxidant capacity were also changed. These findings suggested that radon inhalation could alter the redox state in organs; however, its characteristics were dependent on the total antioxidant capacity of the organs as well as the radon concentration and inhalation time. The insights obtained from this study could be useful for developing therapeutic strategies targeting individual organs.

DOI： 10.1093/jrr/rraa129

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DOI： 10.1093/jrr/rraa129

Other Link： https://academic.oup.com/jrr

Language：English   Publishing type：Research paper (scientific journal)  

Radon therapy has been traditionally performed globally for oxidative stress-related diseases. Many researchers have studied the beneficial effects of radon exposure in living organisms. However, the effects of thoron, a radioisotope of radon, have not been fully examined. In this study, we aimed to compare the biological effects of radon and thoron inhalation on mouse organs with a focus on oxidative stress. Male BALB/c mice were randomly divided into 15 groups: sham inhalation, radon inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3, and thoron inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3 were carried out. Immediately after inhalation, mouse tissues were excised for biochemical assays. The results showed a significant increase in superoxide dismutase and total glutathione, and a significant decrease in lipid peroxide following thoron inhalation under several conditions. Additionally, similar effects were observed for different doses and inhalation times between radon and thoron. Our results suggest that thoron inhalation also exerts antioxidative effects against oxidative stress in organs. However, the inhalation conditions should be carefully analyzed because of the differences in physical characteristics between radon and thoron.

DOI： 10.1007/s00411-020-00843-0

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Language：Japanese   Publisher：(一社)日本放射線影響学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Radon therapy using radon (222Rn) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury.

DOI： 10.1093/jrr/rrx021

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

The purpose of this study is to investigate the biokinetics of inhaled radon, radon activity concentrations in mouse tissues and organs were determined after mice had been exposed to about 1 MBq/m3 of radon in air. Radon activity concentrations in mouse blood and in other tissues and organs were measured with a liquid scintillation counter and with a well-type HP Ge detector, respectively. Radon activity concentration in mouse blood was 0.410 ± 0.016 Bq/g when saturated with 1 MBq/m3 of radon activity concentration in air. In addition, average partition coefficients obtained were 0.74 ± 0.19 for liver, 0.46 ± 0.13 for muscle, 9.09 ± 0.49 for adipose tissue, and 0.22 ± 0.04 for other organs. With these results, a value of 0.414 for the blood-to-air partition coefficient was calculated by means of our physiologically based pharmacokinetic model. The time variation of radon activity concentration in mouse blood during exposure to radon was also calculated. All results are compared in detail with those found in the literature.

DOI： 10.1007/s00411-017-0682-9

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Although radon therapy is indicated for hyperuricemia, the underlying mechanisms of action have not yet been elucidated in detail. Therefore, we herein examined the inhibitory effects of radon inhalation and hot spring water drinking on potassium oxonate (PO)-induced hyperuricemia in mice. Mice inhaled radon at a concentration of 2000 Bq/m(3) for 24 h or were given hot spring water for 2 weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results obtained showed that serum uric acid levels were significantly increased by the administration of PO. Radon inhalation or hot spring water drinking significantly inhibited elevations in serum uric acid levels through the suppression of xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative functions in the liver and kidney. These results suggest that radon inhalation inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while hot spring water drinking may suppress PO-induced elevations in serum uric acid levels through the pharmacological effects of the chemical compositions dissolved in it.

DOI： 10.1093/jrr/rrw014

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The possibility of antioxidant therapy has been reported for several diseases such as ischemic stroke. The therapy could also be applied for diseases caused by reactive oxygen species (ROS). It has been reported that ROS or free radicals may cause various types of hepatopathy, including alcoholic liver disease. Low dose (0.5 Gy) X- or γ- irradiation activates the antioxidative functions of the mouse liver and inhibits ROS- or free radical-induced hepatopathy. Radon therapy is performed mainly for pain-related diseases in Japan and Europe. Several clinical studies have been reported, but the possible mechanisms of the beneficial effects remain unknown. Recently, we have reported that the possible mechanism of radon therapy is the activation of antioxidative functions following radon inhalation. For example, radon inhalation inhibits and alleviates chronic constriction injury induced pain or inflammatory pain in mice due to the activation of antioxidative functions. In addition, although hepatopathy is not the main indication for radon therapy, our recent studies suggested that radon inhalation inhibits hepatopathy caused by ROS or free radicals. In this chapter, based on experiments with mice, we reviewed the possible applications of radon inhalation as an antioxidant therapy for hepatopathy from the viewpoints of recent antioxidant therapy, hepatopathy induced by ROS or free radicals, and the beneficial effects of radon inhalation for hepatopathy.

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DOI： 10.2147/COPD.S50860.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：DOVE MEDICAL PRESS LTD  

PURPOSE: Controlled clinical trials evaluating the efficacy of repeated Waon therapy for patients with chronic obstructive pulmonary disease (COPD) have yet to be conducted. The purpose of the present study was to evaluate whether repeated Waon therapy exhibits an adjuvant effect on conventional therapy for COPD patients. PATIENTS AND METHODS: This prospective trial comprised 20 consecutive COPD patients who satisfied the criteria of the Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines, stages 1-4. They were assigned to either a Waon or control group. The patients in the Waon group received both repeated Waon therapy and conventional therapy, including medications, such as long-acting inhaled β2 agonists, long-acting anticholinergics and xanthine derivatives, and pulmonary rehabilitation. The Waon therapy consisted of sitting in a 60°C sauna room for 15 minutes, followed by 30 minutes of being warmed with blankets once a day, 5 days a week, for a total of 20 times. The patients in the control group received only conventional therapy. Pulmonary function and the 6-minute walk test were assessed before and at 4 weeks after the program. RESULTS: The change in vital capacity (0.30 ± 0.4 L) and in peak expiratory flow (0.48 ± 0.79 L/s) in the Waon group was larger than the change in the vital capacity (0.02 ± 0.21 L) (P=0.077) and peak expiratory flow (-0.11 ± 0.72 L/s) (P=0.095) in the control group. The change in forced expiratory flow after 50% of expired forced vital capacity in the Waon group, 0.08 (0.01-0.212 L/s), was larger than that in the control group, -0.01 (-0.075-0.04 L/s) (P=0.019). Significant differences were not observed in the change in any parameters in the 6-minute walk test. Data are presented as means ± standard deviation or median (25th-75th percentile). CONCLUSION: The addition of repeated Waon therapy to conventional therapy for COPD patients can possibly improve airway obstruction.

DOI： 10.2147/COPD.S50860

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This paper provides absorbed doses arising from radon gas in air retained in lung airway lumens. Because radon gas exposure experiments often use small animals, the calculation was performed for mice and rats. For reference, the corresponding computations were also done for humans. Assuming that radon concentration in airway lumens is the same as that in the environment, its progeny's production in and clearance from airways were simulated. Absorbed dose rates were obtained for three lung regions and the whole lung, considering that secretory and basal cells are sensitive to radiation. The results showed that absorbed dose rates for all lung regions and whole lung generally increase from mice to rats to humans. For example, the dose rates for the whole lung were 25.4 in mice, 41.7 in rats, and 59.9 pGy (Bq m⁻³)⁻¹ h⁻¹ in humans. Furthermore, these values were also compared with lung dose rates from two other types of exposures, that is, due to inhalation of radon or its progeny, which were already reported. It was confirmed that the direct inhalation of radon progeny in the natural environment, which is known as a cause of lung cancer, results in the highest dose rates for all species. Based on the present calculations, absorbed dose rates of the whole lung from radon gas were lower by a factor of about 550 (mice), 200 (rats), or 70 (humans) than those from radon progeny inhalation. The calculated dose rate values are comparatively small. Nevertheless, the present study is considered to contribute to our understanding of doses from inhalation of radon and its progeny.

DOI： 10.1007/s00411-013-0478-5

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We examined the protective effect of radon inhalation on streptozotocin (STZ)-induced type-1 diabetes in mice. Mice inhaled radon at concentrations of 1000, 2500, and 5500 Bq/m3 for 24 hours before STZ administration. STZ administration induced characteristics of type-1 diabetes such as hyperglycemia and hypoinsulinemia; however, radon inhalation at doses of 1000 and 5500 Bq/m3 significantly suppressed the elevation of blood glucose in diabetic mice. Serum insulin was significantly higher in mice pre-treated with radon at a dose of 1000 Bq/m3 than in mice treated with a sham. In addition, superoxide dismutase activities and total glutathione contents were significantly higher and lipid peroxide was significantly lower in mice pre-treated with radon at doses of 1000 and 5500 Bq/m3 than in mice treated with a sham. These results were consistent with the result that radon inhalation at 1000 and 5500 Bq/m3 suppressed hyperglycemia. These findings suggested that radon inhalation suppressed STZ-induced type-1 diabetes through the enhancement of antioxidative functions in the pancreas.

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki.77.25

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Biological response of exposure to radon progeny has long been investigated, but there are only few studies in which absorbed doses in lungs of laboratory animals were estimated. The present study is the first attempt to calculate the doses of inhaled radon progeny for mice. For reference, the doses for rats and humans were also computed with the corresponding models. Lung deposition of particles, their clearance, and energy deposition of alpha particles to sensitive tissues were systematically simulated. Absorbed doses to trachea and bronchi, bronchioles and terminal bronchioles, alveolar-interstitial regions, and whole lung were first provided as a function of monodisperse radon progeny particles with an equilibrium equivalent radon concentration of 1 Bq m(-3) (equilibrium factor, 0.4 and unattached fraction, 0.01). Based on the results, absorbed doses were then calculated for (1) a reference mine condition and (2) a condition previously used for animal experiments. It was found that the whole lung doses for mice, rats, and humans were 34.8, 20.7, and 10.7 nGy (Bq m(-3))(-1) h(-1) for the mine condition, respectively, while they were 16.9, 9.9, and 6.5 nGy (Bq m(-3))(-1) h(-1) for the animal experimental condition. In both cases, the values for mice are about 2 times higher than those for rats, and about 3 times higher than those for humans. Comparison of our data on rats and humans with those published in the literature shows an acceptable agreement, suggesting the validity of the present modeling for mice. In the future, a more sophisticated dosimetric study of inhaled radon progeny in mice would be desirable to demonstrate how anatomical, physiological, and environmental parameters can influence absorbed doses.

DOI： 10.1007/s00411-012-0431-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IJRR-IRANIAN JOURNAL RADIATION RES  

Background: The aim of this study was to analyze the effects of thoron and thermal treatment for aging-related diseases in humans. Materials and Methods: All subjects inhaled thoron with a high concentration (about 4900 Bq/m(3)) for 2 weeks. Blood pressures were measured and blood samples were collected after each treatment 1, 2 and 3 weeks after the first treatment. Results: The alpha-atrial natriuretic peptide level of the rheumatoid arthritis group was increased and the blood pressure was significantly decreased. Superoxide dismutase activity of rheumatoid arthritis group was significantly increased by treatment. In addition, thoron and thermal treatment significantly enhanced the concanavalin A-induced mitogen response and increased the level of CD4-positive cells; it decreased the level of CD8-positive cells. The results suggest that thoron and thermal treatment activates antioxidative function. Furthermore, these findings suggest that thoron and thermal treatment prevents diabetic ketoacidosis and contributes to the prevention of aging-related diseases. Conclusion: Thoron and thermal therapy may be part of the mechanism for the alleviation of diabetes mellitus and rheumatoid arthritis. Iran. J. Radiat. Res., 2012; 9(4): 221-229

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Adequate oxygen stress induced by radon inhalation activates chemical biological protective functions, such as induction of the synthesis of superoxide dismutase and glutathione peroxidase. We studied the probability that activation of this function alleviated various oxidation injuries. The results showed that 1) Radon inhalation enhanced the antioxidative function and membrane fluidity in some mouse organs, and biogenic amine neurotransmitters in the rabbit brain; 2) To elucidate a more effective condition for radon inhalation, mice inhaled radon before carbon tetrachloride (CCl4) administration. The results show that radon inhalation alleviates CCl4-induced hepatopathy; 3) Radon inhalation elevated antioxidant enzymes in patients with bronchial asthma and osteoarthritis; 4) Radon inhalation alleviated the symptoms of hypertension, diabetes and pain in humans; 5) Radon inhalation elevated the p53 protein level and SOD activity in the blood of residents of the Misasa radon hot spring district. Moreover, we compared biochemically the radon effects and thermal effects on humans in radon hot spring therapy, the effects of thoron and thermal treatment for aging-related diseases in humans, and the effects of radon inhalation on acute alcohol-induced oxidative injury of the liver and brain in mice. These findings suggest that radon inhalation alleviates various reactive oxygen species-related injuries. It is highly possible that adequate activation of the functions of the living body by radon inhalation can contribute to preventing or reducing reactive oxygen species-related injuries (lifestyle diseases) which are thought to involve peroxidation. © 2012 Nova Science Publishers, Inc.

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Publishing type：Part of collection (book)  

Adequate oxygen stress induced by radon inhalation activates chemical biological protective functions, such as induction of the synthesis of superoxide dismutase and glutathione peroxidase. We studied the probability that activation of this function alleviated various oxidation injuries. The results showed that 1) Radon inhalation enhanced the antioxidative function and membrane fluidity in some mouse organs, and biogenic amine neurotransmitters in the rabbit brain; 2) To elucidate a more effective condition for radon inhalation, mice inhaled radon before carbon tetrachloride (CCl4) administration. The results show that radon inhalation alleviates CCl4-induced hepatopathy; 3) Radon inhalation elevated antioxidant enzymes in patients with bronchial asthma and osteoarthritis; 4) Radon inhalation alleviated the symptoms of hypertension, diabetes and pain in humans; 5) Radon inhalation elevated the p53 protein level and SOD activity in the blood of residents of the Misasa radon hot spring district. Moreover, we compared biochemically the radon effects and thermal effects on humans in radon hot spring therapy, the effects of thoron and thermal treatment for aging-related diseases in humans, and the effects of radon inhalation on acute alcohol-induced oxidative injury of the liver and brain in mice. These findings suggest that radon inhalation alleviates various reactive oxygen species-related injuries. It is highly possible that adequate activation of the functions of the living body by radon inhalation can contribute to preventing or reducing reactive oxygen species-related injuries (lifestyle diseases) which are thought to involve peroxidation. © 2012 by Nova Science Publishers, Inc. All rights reserved.

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Publishing type：Research paper (scientific journal)  

Background: The aim of this study was to analyze the effects of thoron and thermal treatment for aging-related diseases in humans. Materials and Methods: All subjects inhaled thoron with a high concentration (about 4900 Bq/m³) for 2 weeks. Blood pressures were measured and blood samples were collected after each treatment 1, 2 and 3 weeks after the first treatment. Results: The α-atrial natriuretic peptide level of the rheumatoid arthritis group was increased and the blood pressure was significantly decreased. Superoxide dismutase activity of rheumatoid arthritis group was significantly increased by treatment. In addition, thoron and thermal treatment significantly enhanced the concanavalin A-induced mitogen response and increased the level of CD4-positive cells; it decreased the level of CD8-positive cells. The results suggest that thoron and thermal treatment activates antioxidative function. Furthermore, these findings suggest that thoron and thermal treatment prevents diabetic ketoacidosis and contributes to the prevention of aging-related diseases. Conclusion: Thoron and thermal therapy may be part of the mechanism for the alleviation of diabetes mellitus and rheumatoid arthritis.

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki.75.33

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

A radon test facility for small animals was developed in order to increase the statistical validity of differences of the biological response in various radon environments. This paper illustrates the performances of that facility, the first large-scale facility of its kind in Japan. The facility has a capability to conduct approximately 150 mouse-scale tests at the same time. The apparatus for exposing small animals to radon has six animal chamber groups with five independent cages each. Different radon concentrations in each animal chamber group are available. Because the first target of this study is to examine the in vivo behaviour of radon and its effects, the major functions to control radon and to eliminate thoron were examined experimentally. Additionally, radon progeny concentrations and their particle size distributions in the cages were also examined experimentally to be considered in future projects.

DOI： 10.1093/rpd/ncr100

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN RADIATION RESEARCH SOC  

We examined dose-dependent or dose rate-dependent changes of superoxide dismutase (SOD) activity using a new large-scale facility for exposing small animals to radon. Mice were exposed to radon at a concentration of 250, 500, 1000, 2000, or 4000 Bq/m(3) for 0.5, 1, 2, 4, or 8 days. When mice were exposed to radon at 2000 day•Bq/m(3), activation of SOD activities in plasma, liver, pancreas, heart, thymus, and kidney showed dose-rate effects. Our results also suggested that continuous exposure to radon increased SOD activity, but SOD activity transiently returned to normal levels at around 2 days. Moreover, we classified the organs into four groups (1. plasma, brain, lung; 2. heart, liver, pancreas, small intestine; 3. kidney, thymus; 4. stomach) based on changes in SOD activity. Thymus had the highest responsiveness and stomach had lowest. These data provide useful baseline measurements for future studies on radon effects.

DOI： 10.1269/jrr.10072

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Radiation Safety Management  

DOI： 10.12950/rsm.10.1

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki.74.28

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Cigarette smoking and advanced age are well known as risk factors for chronic obstructive pulmonary disease (COPD), and nutritional abnormalities are important in patients with COPD. However, little is known about the nutritional status in non-COPD aging men with smoking history. We therefore investigated whether reduced lung function is associated with lower blood markers of nutritional status in those men. SUBJECTS AND METHODS: This association was examined in a cross-sectional study of 65 Japanese male current or former smokers aged 50 to 80 years: 48 without COPD (non-COPD group), divided into tertiles according to forced expiratory volume in one second as percent of forced vital capacity (FEV(1)/FVC), and 17 with COPD (COPD group). RESULTS: After adjustment for potential confounders, lower FEV(1)/FVC was significantly associated with lower red blood cell count (RBCc), hemoglobin, and total protein (TP); not with total energy intake. The difference in adjusted RBCc and TP among the non-COPD group tertiles was greater than that between the bottom tertile in the non-COPD group and the COPD group. CONCLUSION: In non-COPD aging men with smoking history, trends toward reduced nutritional status and anemia may independently emerge in blood components along with decreased lung function even before COPD onset.

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.58.389_2

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DOI： 10.4044/joma.121.9

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Other Link： http://ousar.lib.okayama-u.ac.jp/14849

Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki.72.61

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Other Link： http://search.jamas.or.jp/link/ui/2009042267

Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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DOI： 10.4044/joma.120.1

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Other Link： http://eprints.lib.okayama-u.ac.jp/12832

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Our previous studies have shown that spa therapy can reduce subjective symptoms and improve ventilatory function in patients with chronic obstructive pulmonary disease (COPD). The aim of this study is to measure the effects of spa therapy on walking distance during the six-minute walk test in patients with COPD. Twenty-five COPD patients hospitalized for pulmonary rehabilitation at our hospital were included in this study. Twenty-two patients were male and 3 patients were female. Two patients had stage I, 9 patients had stage II, and 14 patients had stage III COPD, according to the Global Initiative for Chronic Obstructive Lung Disease. We offered complex spa therapy (swimming training in a hot spring pool, inhalation of iodine salt solution, and fango therapy) in all patients for 4 weeks. Ventilatory function, six-minute walk distance, oxygen saturation and Borg scale were measured. Vital capacity (VC) was significantly improved by spa therapy at 4 weeks (p<0.05). The values of forced vital capacity (FVC), forced expiratory volume in one second (FEV_1.0), forced expiratory flow after 75% of expired FVC (FEF₇₅), forced expiratory flow after 50% of expired FVC (FEF₅₀), forced expiratory flow after 25% of expired FVC (FEF₂₅), mean expiratory flow during the middle half of the FVC (FEF_25-75), residual volume (RV), functional residual capacity (FRC), peak expiratory flow (PEF) and diffusing capacity for carbon monoxide (DLco) showed a tendency to increase, however the increase in the 10 parameters was not significant. The values of six-minute walk distance before and after spa therapy were 288±106m and 323±114m, respectively (p<0.05). There was a significant decrease in values of maximum Borg Scale values (p<0.05). The values of minimum oxygen saturation and the values of oxygen saturation at rest slightly increased, but not significantly. The change of six-minute walk distance correlated with change of VC (r=0.545; p<0.05), with change of FVC (r=0.628; p<0.05), with change of FEV_1.0 (r=0.559; p<0.05), with change of FEF₅₀ (r=0.480; p<0.05), with change of minimum oxygen saturation (SpO₂) (r=0.554; p<0.05) and with change of SpO₂ at rest (r=0.445; p<0.05). We found that spa therapy induced improvements in ventilatory dysfunction and six-minute walk distance in patients with COPD. The results from this study reveal that spa therapy may improve disease control and exercise tolerance in patients with COPD.

DOI： 10.11390/onki1962.71.241

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.57.1495_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.57.440_3

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Language：Japanese   Publisher：(一社)日本温泉気候物理医学会  

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Language：Japanese   Publisher：(一社)日本温泉気候物理医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.56.400_2

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Language：Japanese   Publisher：(一社)日本温泉気候物理医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Recently, we have also reported that spa therapy combined with dietary supplementation of perilla seed oil would be effective for patients, and would suppress the generation of leukotriene C4 (LTC4) by peripheral leucocytes. However, it is still unclear how the combination spa therapy and dietary supplementation of perilla seed oil influences on the pathophysiology of bronchial asthma. In the present study, the effects of spa therapy combined with dietary supplementation of perilla seed oil were examined in patients with asthma in relation to the serum eosinophil cationic protein (ECP) levels to investigate the effect on bronchial asthma. Ten adult asthmatic patients with moderate type asthma in terms of severity were taken to have a complex spa therapy and consume perilla seed oil-rich diet for 4 weeks. The generation of LTC4 by peripheral leucocytes, serum ECP level and pulmonary function were measured. Significant decreases were observed for LTC4 and ECP for 4 weeks. Forced vital capacity (FVC), which was one of the pulmonary function tests, improved significantly at 4 weeks (p<0.05). The number of eosinophils decreased for 4 weeks, but the differences were not significant. The results obtained here suggest that spa therapy combined with dietary supplementation of perilla seed oil leads to decrease in LTC4 and ECP and improves pulmonary function and asthma control.

DOI： 10.11390/onki1962.69.261

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Purpose: We examined the effects of foot baths containing artificial carbon dioxide (CO₂) on peripheral circulation. Our goal was to obtain quantitative results bearing on the treatment and preservation of refractory leg ulcers and gangrene, which would occur in arteriosclerosis obliterans (ASO) and diabetic peripheral circulation disorders.<br>Procedures: The lower legs of six healthy volunteers were placed for 10min into a 42°C bath of 10l in which 45g of artificial CO₂ "BUB" was dissolved. A laser Doppler blood-flowmeter was firmly attached. The measurements of blood flow were taken before, during, and 5, 15, 25, and 35min after each subject took a foot bath. Next, in order to examine the effects of peripheral blood flow on the whole body during the foot baths, each laser Doppler blood-flowmeters was attached on the subject's right arm, 10cm above the wrist joint.<br>Results: The blood flow increased during the foot bath and decreased after the bath was removed; during in a 10min bath, the flow was 264±135 (%) (p<0.05) of the flow before the feet were placed into the bath. 5min after the bath was removed, the flow was 256±174 (%) of the original pre-bath rate. 15min later it was 146±60 (%), 25min later it was 112±23 (%), and 35min later it was 107±24 (%), as low as the flow before the feet were placed in the bath. The arm blood flow also increased during the foot bath and decreased after the bath was removed. During a 10min bath, the flow was 119±49 (%) of the rate before the feet were placed in the bath. 5min after the bath was removed, the flow was 120±66 (%) of the original pre-bath rate. 15min later it was 113±28 (%), 25min later it was 109±16 (%), and 35min later it was 95±14 (%), essentially the same as the flow before the feet were placed in the bath.<br>Discussion: Our work demonstrates an increase in blood flow, by 2.6X, by using a foot bath containing artificial CO₂. The increase was maintained for 5min after removed of the foot from the bath. However, the blood flow decreased 15min after the baths were removed. We hope that this simple and effective foot bath will be used both at home and elderly care service stations. Its use could see prevention from refractory leg ulcers or gangrene, particularly as average life span continues to increase in Japan.

DOI： 10.11390/onki1962.69.269

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.55.1150_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.55.443_3

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Language：Japanese   Publisher：(一社)日本温泉気候物理医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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To clarify the mechanism by which radon hot springs prevent cancer or not, in this study, blood was collected from residents in the Misasa hot spring district and in a control district. The level of a representative cancer-suppressive gene, p53, and the activity of a representative antioxidant enzyme, superoxide dismutase (SOD), were analyzed as indices. The level of serum p53 protein in the males in the Misasa hot spring district was found to be 2-fold higher than that in the control district, which is a significant difference. In the females in the Misasa hot spring district, SOD activity was approximately 15% higher than that in the control district, which is also statistically significant, and exceeded the reference range of SOD activity despite advanced age. These results suggested that routine exposure of the residents in the Misasa hot spring district to radon at a concentration about 3 times higher than the national mean induces trace active oxygen in vivo, potentiating products of cancer-suppressive gene and antioxidant function. As the p53 protein level was high in the residents in the Misasa hot spring district, apoptosis of cancer cells may readily occur.

DOI： 10.1269/jrr.46.21

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PURPOSE OF REVIEW: Chronic inflammation in asthma can also lead to airway remodeling, which contributes to airway narrowing. It may be possible to assess and quantify the extent of airway remodeling in vivo using computed tomography. This review examines recent developments in the evaluation of asthma severity using computed tomography, and the effect of treatment assessed by computed tomography. RECENT FINDINGS: Asthma patients have thicker airways on computed tomography scans than do healthy control individuals, and the degree of thickening is related to the severity of disease, airflow obstruction, and airway reactivity. Recent studies have indicated that patients with severe asthma and irreversible airflow obstruction had longer disease duration, a greater inflammatory process and more airway abnormalities, assessed by high-resolution computed tomography, suggestive of airway remodeling. Other studies have shown that high-resolution computed tomography lung density correlates with airflow limitation and lung volume (but not with lung transfer factor), and also correlates with patient age and severity of asthma. More recently, two publications demonstrated the effect of treatment on airway wall thickness and lung density assessed by computed tomography in patients with asthma. SUMMARY: High-resolution computed tomography is one of the most useful tools for imaging airways and parenchyma. Computed tomography scanning may be useful in determining which patients might benefit from more or less treatment. With additional advances in technology, it is likely that quantitative assessment by computed tomography will ultimately be a valuable tool for the study and treatment of chronic airway diseases.

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Effects of long-term spa therapy on reduction of the costs of drugs used for the treatment were examined in 23 patients with asthma. The costs of drugs used per patient for 1 year when spa therapy started (1997) were compared with the costs used for 1 year after spa therapy for 3 years (2000). 1. The decrease in the total costs of all drugs was \31, 910 in patients with stage 1, \74, 900 in those with stage 2, \113, 450 in stage 3, and \180, 910 in stage 4. The % decrease of the costs of drugs used was 34.2% in stage 1, 46.3% in stage 2, 37.1% in stage 3, and 42.4% in stage 4. The results showed that the reduction in the costs of drugs tended to increase as asthma severity increased, and that the % decrease of the costs was higher in stage 2 and 4, in which the %decrease was more than 40%. 2. The reduction of costs of each drug, bronchodilators, glucocorticoids, antiallergic agents, mucolytics, and antibiotics after spa therapy, was significant in patients with stage 3 and stage 4, whose severity was considerably increased. However, the decrease in the costs of these drugs after spa therapy was not significant in patients with stage 1 and 2. The reduction of the costs more than 50% was observed in bronchodilators, antiallergic agents, mucolytics, and antibiotics in patients with stage 4, in whom the reduction of the costs of these drugs was significant. The results obtained here suggest that the costs of drugs used for asthma treatment could be reduced by spa therapy in patients with more increased severity.

DOI： 10.11390/onki1962.68.166

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

The effects of spa therapy for asthmatics with a long history of cigarette smoking were studied, compared with the effects for those without smoking history. 1. Of 22 patients with smoking history, 15 (68.2%) had definite efficacy of spa therapy (4 had marked efficacy, and 11 had moderate efficacy), and the residual 7 had slight or no efficacy. In contrast, of 36 patients without smoking history, 29 (80.6%) had definite efficacy. The effects of spa therapy for asthmatics were significantly higher in never-smokers than in ex-smokers.<br>2. A significant increase in the production of IgE antibodies, bronchial hyperresponsiveness and the generation of leukotrienes B₄ (LTB₄) and C₄ (LTC₄) by leucocytes was observed in ex-smokers compared with never-smokers. 3. The frequency of patients with a positive BAST against inhalant allergens was larger in subjects with slight or no efficacy than in those with marked or moderate efficacy in never-smokers, but not in ex-smokers. 4. Bronchial hyperresponsiveness was significantly increased in patients with slight or no efficacy than in those with marked or moderate efficacy both in ex-smokers and never-smoker. 5. The generation of LTB₄ was more increased in subjects with slight or no efficacy than in those with efficacy both in ex-smokers and never-smokers, however, the differences were not significant. 5. The generation of LTC₄ tended to be more increased in subjects with slight or no efficacy than in those with efficacy in never-smokers, but not in ex-smokers, although these were not significant. The results suggest that an increase in the production of IgE antibodies, bronchial hyperresponsiveness, and the generation of LTB₄ and LTC₄, which might be influenced by cigarette smoking, affect the effects of spa therapy for patients with asthma.

DOI： 10.11390/onki1962.68.83

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：ELSEVIER SCIENCE BV  

We examined the temporal changes in antioxidants, immune-, vasoactive- and pain-associated substances in human blood by therapy to elucidate the mechanism of osteoarthritis in which radon therapy is used as a treatment. Results showed that radon inhalation enhanced the antioxidation and immune function, and that the changes in vasoactive and pain-associated substances indicate increases in tissue perfusion brought about by radon therapy. (c) 2004 Published by Elsevier B.V.

DOI： 10.1016/j.ics.2004.12.013

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.54.354_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.54.333_3

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.54.394_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.54.1039_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.54.1125_2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Mary Ann Liebert Inc.  

DOI： 10.1089/act.2005.11.89

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Language：English   Publisher：岡山大学医学部・歯学部附属病院三朝医療センター  

気管支喘息32例を対象に,治療のために要した年間薬剤費を,国際ガイドラインの重症度分類(stage1-4)により検討した.その結果, 1)年間の総薬剤費はstage4の症例で最も高く(平均\284370),一方,stage1(平均\74670)で最も低い値を示した. 2)個々の薬剤費の検討では,抗アレルギー薬,気管支拡張薬のどの薬剤費が高く,次で副腎皮質ホルモン(主として吸入薬),去痰薬の順であった. 3)気管支拡張薬,副腎皮質ホルモン,抗アレルギー薬などの薬剤費は,いずれもstage4で最も高い値を示した

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.68.20

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Language：Japanese   Publisher：(一社)日本温泉気候物理医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN RADIATION RESEARCH SOC  

The radioactive and thermal effects of radon hot spring were biochemically compared under a sauna room or hot spring conditions with a similar chemical component, using the parameters that are closely involved in the clinic for radon therapy. The results showed that the radon and thermal therapy enhanced the antioxidation functions, such as the activities of superoxide dismutase (SOD) and catalase, which inhibit lipid peroxidation and total cholesterol produced in the body. Moreover the therapy enhanced concanavalin A (ConA)-induced mitogen response and increased the percentage of CD4 positive cells, which is the marker of helper T cells, and decreased the percentage of CD8 positive cells, which is the common marker of killer T cells and suppressor T cells, in the white blood cell differentiation antigen (CD8/CD4) assay. Furthermore, the therapy increased the levels of alpha atrial natriuretic polypeptide (alpha ANP), beta endorphin, adrenocorticotropic hormone (ACTH), insulin and glucose-6-phosphate dehydrogenase (G-6-PDH), and it decreased the vasopression level. The results were on the whole larger in the radon group than in the thermal group. The findings suggest that radon therapy contributes more to the prevention of life-style-related diseases related to peroxidation reactions and immune suppression than to thermal therapy. Moreover, these indicate what may be a part of the mechanism for the alleviation of hypertension, osteoarthritis (pain), and diabetes mellitus brought about more by radon therapy than by thermal therapy.

DOI： 10.1269/jrr.45.83

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

UNLABELLED: Radon therapy uses radon (222Rn) gas, which mainly emits alpha-rays and induces a small amount of active oxygen in the body. We first examined the temporal changes in antioxidants, immune, vasoactive, and pain-associated substances in human blood by therapy to elucidate the mechanism of osteoarthritis in which radon therapy is used as a treatment. Results showed that radon inhalation enhanced the antioxidation and immune function, and the findings suggest that radon therapy contributes to the prevention of osteoarthritis related to peroxidation reactions and immune depression. Moreover, the changes in vasoactive and pain-associated substances indicated increases in tissue perfusion brought about by radon therapy, suggesting that radon inhalation plays a role in alleviating pain. PERSPECTIVE: The findings suggest that an appropriate amount of active oxygen is produced in the body after radon inhalation, and this contributes to the alleviation of the symptoms of active oxygen diseases such as osteoarthritis.

DOI： 10.1016/j.jpain.2003.09.005

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING LTD  

BACKGROUND: Smoking is the most important cause of chronic obstructive pulmonary disease (COPD). However, the influence of cigarette smoking on the pathogenesis of asthma in the elderly remains controversial. This study attempted to clarify the influence of cigarette smoking on elderly asthmatics. METHODS: Forty-eight asthmatics over 70 years old (25 ex-smokers and 23 never-smokers) and 20 patients with COPD over 70 years old (all ex-smokers) were studied to determine the influence of cigarette smoking on IgE-mediated allergy (total IgE, IgE antibodies against inhalant allergens, bronchial hyper-responsiveness (BHR), generation of leukotriene (LT) B4 and C4), pulmonary function, and the relative area of lung showing attenuation values less than -950 Hounsfield units (RA950) on high-resolution computed tomography scans. RESULTS: The incidence of positive IgE antibodies against inhalant allergens, BHR, and the generation of leukotriene B4 (LTB4) by leucocytes were significantly increased in patients with a history of smoking compared with those without. Residual volume (%RV) was significantly increased, and diffusing capacity for carbon monoxide was significantly decreased in ex-smokers with asthma and COPD compared with never-smokers with asthma. Inspiratory RA950 and ratio of expiratory RA950 to inspiratory RA950 were significantly larger in asthmatics with a smoking history than in those without, and in COPD patients than in asthmatics. CONCLUSION: Cigarette smoking enhances the production of IgE antibodies, BHR, and generation of LTB4 by leucocytes in elderly asthmatics. Increased hyper-inflation or emphysematous changes of the lungs expressed by increased RA950, closely related to %RV, was more frequently observed in ex-smokers compared with never-smokers.

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Effects of spa therapy on % low attenuation area (LAA)<-950 HU of the lungs on HRCT at full inspiration, CT number, a ratio of expiratory LAA to inspiratory LAA (exp LAA/ins LAA), residual volume (RV) and diffusing capacity for carbon monoxide (DLco) in asthma were compared between never-smokers and ex-smokers of asthmatics.<br>1. The % LAA of the lungs on HRCT in asthma significantly decreased after spa therapy both in never-smokers and ex-smokers of asthmatics. CT number also significantly increased in the two groups. 2. The exp LAA/ins LAA significantly decreased after spa therapy in never-smokers, but not in ex-smokers. 3. The %RV also significantly decreased by spa therapy in never-smokers, but not in ex-smokers. 4. The DLco value did not significantly change by spa therapy both in nevers-mokers and ex-smokers. 5. The values of %FVC and %FEV 1.0 tended to increased in the two groups, but the increase was not significant. The value of FEV 1.0% significantly increased after spa therapy in never-smokers, but not in ex-smokers. The results suggest that hyperinflation and destruction of terminal airspaces are stronger in ex-smokers than in never-smokers, and that spa therapy is more effective in never-smokers than in ex-smokers.

DOI： 10.11390/onki1962.67.195

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

The effects of long-term spa therapy were studied in 10 patients with pulmonary emphysema: five patients had long-term spa therapy for 5 years (group A), and another 5 patients had not spa therapy for the same 5 years (group B). There were no significant differences in %FVC, %FEV 1.0, %LAA of the lung on HRCT, %DLco and %RV between the two groups. 1. The LAA of the lung on HRCT slightly, but did not significantly increase in patients with spa therapy for 5 years. In patients without spa therapy, the %LAA of the lung significantly increased after 4-(61.1%) (p<0.01) and 5-year observation (65.5%) (p<0.001) compared with the initial value (52.2%). 2. The %DLco and %RV values slightly decreased in patients with spa therapy, but the decrease in the two parameters was not significant. 3. The %DLco significantly decreased (67.2% to 49.0%), and the %RV also significantly increased (175.4% to 230.6%) after 5-year observation in patients without spa therapy. The results obtained here suggest that spa therapy for pulmonary emphysema should start as early as possible when the diagnosis of the disease is decided, and the therapy should be continued as long as possible.

DOI： 10.11390/onki1962.67.148

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.53.306_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.53.942_2

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：EUROPEAN RESPIRATORY SOC JOURNALS LTD  

Recently, it was shown that both mean lung density (MLD) and the relative lung area with an attenuation of <-950 HU (RA950) are related to severity of asthma in nonsmoking asthmatics. The aim of the present study was to examine whether reduced computed tomography (CT) lung density during exacerbation could change after treatment. A cross-sectional study was performed to compare CT lung density in 30 stable asthmatics, 30 unstable asthmatics and 25 control subjects. In order to investigate longitudinally the effect of treatment on decreased CT lung density, 17 asthmatics with an exacerbation were followed at the initiation of treatment and 2 months after relief. The MLD was significantly lower and the RA950 significantly higher in unstable asthmatics than in controls and stable asthmatics. Both MLD and RA950 changed significantly with administration of systemic glucocorticoid therapy. The changes in forced expiratory volume in one second correlated significantly with those in both MLD and RA950. The changes in residual volume also correlated significantly with those in both MLD and RA950. It was concluded that decreased computed tomographic lung density during an asthma exacerbation is at least partially reversible, and changes in mean lung density and the relative lung area with a radiation attenuation of <-950 HU are related to the change in forced expiratory volume in one second and residual volume.

DOI： 10.1183/09031936.03.00081702

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN RADIATION RESEARCH SOC  

An increased systemic production of oxygen-free radicals by activated inflammatory cells is thought to be involved in the pathophysiology of asthma. The aim of this study is to evaluate the clinical effects of radon and thermal therapy on asthma in relation to antioxidant enzymes and lipid peroxide. Radon and thermal therapy were performed once a week. All subjects went to a hot bathroom with a high concentration of radon, and nasal inhalation of vapor from a hot spring was performed for 40 min once a day under conditions of high humidity. The room temperature was 48 degrees C; the room radon concentration was 2,080 Bq/m3. Blood samples were collected at 2 h, 14, and 28 days after the first therapy. A blood sample also was collected before the first therapy (at body temperature and background radon level) to be used as the control. The forced expiratory volume in one second (%FEV1) was significantly increased 28 days after the first therapy. On day 28, the catalase (CAT) activity was significantly increased in comparison with the control. The superoxide dismutase (SOD) activity was significantly increased compared to the control after first inhalation. On days 14 and 28, the lipid peroxide level was significantly decreased in comparison with the control. In conclusion, the present pilot study has shown that radon and thermal therapy improved the pulmonary function of asthmatics by increasing the reduced activities of antioxidant enzymes.

DOI： 10.1269/jrr.44.95

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

BACKGROUND: Treatment of gastroesophageal reflux (GER) with proton-pump inhibitors (PPI) improves symptoms of asthma in some patients. However, the effects of a PPI on ventilatory function are still controversial. In this study, we measured ventilatory function in asthma patients treated with a PPI in order to identify those in whom a therapeutic effect on asthma can be expected from the acid suppression. METHODS: From a cohort of 114 consecutive patients with bronchial asthma, 53 patients agreed to participate in the study and were treated with rabeprazole 20mg daily for 8 weeks during an asymptomatic, stable period with no exacerbations of their asthma. Of the 53 patients, 22 were diagnosed as GER on the basis of the QUEST questionnaire and endoscopic examination. The patients were monitored for improvement in ventilatory function. RESULTS: Four patients dropped out because of adverse drug reactions. All the patients with GER noted an improvement in reflux symptoms with PPI treatment. An improvement of more than 20% in peak expiratory flow (PEF) was observed in 8 of 21 GER patients but in none of the non-GER patients. Factors predictive of improvement in PEF with rabeprazole therapy were the QUEST score (odds ratio: 1.47, 95% CI: 1.06-2.04, P = 0.022) and steroid-dependency of asthma (odds ratio: 0.01, 95% CI: 0.001-0.31, P = 0.008). CONCLUSIONS: Treatment with rabeprazole is expected to ameliorate asthma in non-steroid-dependent patients who have symptomatic GER defined by the QUEST score.

DOI： 10.1080/00365520310002490

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER THORACIC SOC  

Low attenuation areas in computed tomography images from patients with chronic obstructive pulmonary disease have been reported to represent macroscopic and/or microscopic emphysema. The cumulative size distribution of the clusters has been shown to follow a power law characterized by the exponent D, a measure of the complexity of the terminal airspace geometry. We have previously found increased low attenuation areas in nonsmoking subjects with asthma. We examined the size distribution of the clusters in nonsmoking subjects with asthma compared with both nonsmoking control subjects and subjects with asthma with a smoking history. The percentage of lung field occupied by low attenuation areas (LAA%) and D in subjects with asthma with a smoking history differed significantly from nonsmoking subjects with asthma and control subjects. In nonsmoking subjects with asthma, both parameters differed significantly between severe asthma and mild or moderate asthma. The LAA% differed significantly between moderate and mild asthma, but D did not. In mild and moderate asthma, a highly significant correlation between LAA% and D was observed in patients with a smoking history, but not in nonsmoking subjects with asthma. Our results suggest that decreased D is mostly related to emphysematous change, and both measurements of LAA% and D may provide useful information to characterize low attenuation areas in subjects with asthma.

DOI： 10.1164/rccm.2112070

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ADIS INTERNATIONAL LTD  

Objective: Osteoporosis is generally known to be one of the most serious adverse effects of long-term corticosteroid administration. Recently it was discovered that corticosteroid-induced osteoporosis occurs not only in trabecular bone but also in cortical bone, leading to a reduction in cortical bone strength. To ameliorate corticosteroid-induced bone injury, we administered etidronic acid plus alfacalcidol to five steroid-dependent asthmatics for 4 years and monitored therapeutic responses in trabecular bone and cortical bone using peripheral quantitative computed tomography (pQCT).
Patients and interventions: The five steroid-dependent asthmatic patients included two males and three females, with a mean age 68.2 years, taking a mean daily dose of oral prednisolone of 7 mg/day. Etidronic acid 200 mg/day was administered for 14 consecutive days every 4 months for 4 years, while alfacalcidol 0.5 mug was administered daily for 4 years.
Main outcome measures and results: Every 4 months, the number of vertebral fractures was assessed by lateral vertebral radiographs, and the total radial bone mineral density (BMD). trabecular BMD, cortical BMD, Relative Cortical Volume (RCV) and Strength Strain Index (SSI) were assessed by pQCT (Stratec XCT-960). At follow-up, no new fractures had occurred, the trabecular BMD was found to be slightly increased (from 117.2 mg/cm(3) at baseline to 121.6 mg/cm(3) after 48 months). and no significant decreases were observed in the total BMD, cortical BMD, RCV or SSI.
Conclusion: Based on these findings, etidronic acid plus alfacalcidol seems to be effective in preventing steroid-induced bone injury, not only in terms of trabecular and cortical BMD, but also in terms of cortical bone volume and strength, which may lead to a decrease in non-vertebral fractures. However, further investigation is required with a larger sample size and a longer administration period to confirm these findings.

DOI： 10.2165/00044011-200323020-00003

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Spa therapy has been performed at our medical center for last 20 years. The changes in number and frequency of patients with respiratory disease were analyzed every 5 year for last 20 years. The total number of patients with respiratory disease who were admitted at our medical center for last 20 years was 1934, of whom the number of patients with asthma was 1226 (63.4%), and the number of those with COPD was 415 (21.5%). The number of patients with asthma treated with spa therapy showed a tendency to increase form 57 for the first 5 years (first stage) to 465 for the last 5 years (forth stage). The number of patients with COPD also increased from 26 for the first 5 years to 227 for the last 5 years. The frequency of SDIA decreased from 68.4% for the first 5 years to 29.0% for the last 5 years. In contrast, the frequency of pulmonary emphysema increased 19.2% at the first stage to 76.7% at the forth stage. The number and frequency of elderly patients with asthma and COPD over the age of 60 tended to increase for last 20 years.

DOI： 10.11390/onki1962.66.99

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Clinical effects of spa therapy for patients with pulmonary emphysema (PE) were evaluated by observing changes in %LAA of the lung on HRCT, %RV, %FVC, %FEV 1.0, and %DLco values after the long-term therapy. The subjects in this study 16 patients with PE. The subjects were divided into two groups according to the extent of %LAA<-950 HU of the lung on HRCT: %LAA<50% (N=6) and 50%≤%LAA (N=8). 1. Spa therapy significantly improved %LAA (42.5% at the initial stage to 36.3% 24 months after spa therapy), %RV (202.1% to 156.1%) and %DLco 71.0% to 85.7%), but not %FVC and %FEV 1.0, in patients with PE of %LAA<50%, however, significant. Improvement of these parameters was not observed in patients without spa therapy. 2. Spa therapy did not improve the values of %LAA, %RV, and %DLco, as well as %FVC and %FEV 1.0, in patients with PE of 50%≤%LAA. These parameters tended to decrease in the patients of 50%≤%LAA. These results suggest that spa therapy improves %LAA and parameters related to pulmonary function when they are at early stage of PE, however, the therapy was not remarkably effective for these parameters when they were at advanced stage of PE.

DOI： 10.11390/onki1962.66.91

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Characteristics of low attenuation area (LAA) of the lungs on HRCT were studied in 132 patients with asthma, and long-term spa therapy on the LAA of the lungs was observed in 5 patients with asthma, whose me an %LAA was more than 30%.<br>1. The morphology of LAA of the lungs on HRCT observed in asthma was different from that in pulmonary emphysema. 2. The LAA of the lungs in asthma was closely related to residual volume (RV). 3. The mean %LAA value significantly decreased from 33.5% before spa therapy to 24.5% at 24 months after beginning of the therapy. CT number also significantly increased after long-term spa therapy. 4. %FEV1.0 value significantly improved from 52.1% before spa therapy to 72.1% at 24 months after spa therapy. The RV value also decreased by spa therapy, however, the decrease was not significant. These results suggest that LAA of the lungs in asthma is associated with hyperinflation, and the LAA of the lungs decreases after long-term spa therapy.

DOI： 10.11390/onki1962.66.115

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.52.381_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.52.845_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.52.939_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.52.312_2

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Language：Japanese   Publisher：(一社)日本放射線影響学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER-VERLAG LONDON LTD  

Despite an intriguing understanding of trabecular bone dynamics, little is known about corticosteroid-induced cortical bone loss and fractures. Recently, we verified a steroid-induced decrease in cortical bone volume and density using peripheral quantitative computed tomography (pQCT) in adult asthmatic patients given oral corticosteroids. Subsequently, the pQCT parameters and presence of vertebral fractures were investigated to further clarify the role of cortical bone quality in fractures in 86 postmenopausal (>5 years after menopause) asthmatic patients on high-dose oral steroid (>10 g cumulative oral prednisolone) (steroid group) and 194 age-matched controls (control group). Cortical and trabecular bone was subjected to measurement of various parameters using pQCT (Stratec XCT960). Relative Cortical Volume (RCV) was calculated by dividing the cortical area by the total bone area. Strength Strain Index (SSI) was determined in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. Patients treated with high doses of oral steroid (>10 g cumulative oral prednisolone) were found to have an increased risk of fracture compared with control women receiving no steroid medication (odds ratio, 8.85; 95% CI, 4.21-18.60) after adjustment was made for years since menopause, body mass index and RCV. In both groups, the diagnostic and predictive ability of the pQCT parameters for vertebral fracture was assessed by the areas under their receiver operating characteristic (ROC) curves. All parameters were found to be significant predictors ( p<0.0001) in the control group. In the steroid group, however, the cortical bone mineral density (BMD) ( p = 0.001), RCV ( p<0.0001) and SSI ( p = 0.001) were found to be significant predictors, but not trabecular BMD ( p = 0.176). For comparison between the two groups, thresholds of all parameters for vertebral fracture were also calculated by the point of coincidence of sensitivity with specificity in ROC testing and the 90th percentile value. Although a rise in fracture threshold in the steroid group was suggested, considerable difference in the values obtained by the two methods of calculation precluded any conclusion. High-dose oral steroid administration was associated with an increased risk of fracture. Cortical bone parameters obtained by pQCT could play a role as good predictors of future corticosteroid-induced vertebral fractures.

DOI： 10.1007/s001980200088

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Effects of spa therapy on asthma were studied in 64 patients with asthma in relation to the generation of leukotrienes B4 (LTB4) and C4 (LTC4) and bronchial hyperresponsiveness. 1. The efficacy of spa therapy was marked in 12 (18.8%), and moderate in 45 (70.3%) of 64 patients with asthma, and slight or no efficacy of the therapy was observed in the residual 7 patients (10.9%). 2. Bronchial hyperresponsiveness to methacholine was the highest in patients with slight or no efficacy of spa therapy, however, there were no significant differences among the three groups classified by clinical efficacy. 3. The generation of LTC4 by leucocytes was significantly higher in patients with slight or no efficacy compared with the generation in those with marked (p<0.01) and moderate efficacy (p<0.001). However, there were no significant differences in the generation of LTB4 among them. 4. The generation of LTC4 before spa therapy significantly decreased in patients with marked (p<0.001) and moderate efficacy (p<0.01) after spa therapy, but not in those with slight or no efficacy. The generation of LTB4 was not significantly different before and after spa therapy among patients with marked, moderate, and slight or no efficacy. These results show that the efficacy of spa therapy for patients with asthma is closely related to the generation of LTC4 by leucocytes, and that the generation of LTC4 significantly decreases after spa therapy in patients with spa efficacy.

DOI： 10.11390/onki1962.65.153

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.51.243_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.51.1038_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.51.907_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.51.913_3

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BRITISH MED JOURNAL PUBL GROUP  

BACKGROUND: Low attenuation areas (LAA) on computed tomographic (CT) scans have been shown to represent emphysematous changes in patients with chronic obstructive pulmonary disease (COPD). However, the significance of LAA is still controversial in patients with asthma. This study was undertaken to assess the usefulness of lung CT densitometry in the detection of airspace enlargement in association with asthma severity. METHODS: Forty five asthmatic subjects and 15 non-smoking controls were studied to determine the influence of age, pulmonary function, and asthma severity on mean lung density (MLD) and the relative area of the lung showing attenuation values less than -950 HU (RA(950)) on high resolution CT (HRCT) scans. RESULTS: In asthmatic patients both MLD and RA(950) correlated with parameters of airflow limitation (%FEV(1), FEV(1)/FVC, %FEF(25-75)) and lung volume (%TLC, %FRC, %RV), but not with lung transfer factor (%TLCO, %TLCO/VA). The results of HRCT lung densitometry also correlated with patient age and severity of asthma. CONCLUSIONS: Decreased CT lung density in non-smoking asthmatics is related to airflow limitation, hyperinflation and aging, but not with lung transfer factor.

DOI： 10.1136/thorax.56.11.851

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARCEL DEKKER INC  

To investigate the low-attenuation areas of the lungs (LAA) in asthma, we compared the mean lung density (MLD) and the LAA in 22 asthmatics (12 ex-smokers and 10 nonsmokers) and 13 patients with chronic obstructive pulmonary disease (COPD) by high-resolution computed tomography. The MLD and the relative area of the lung with attenuation values lower than -950 Hounsfield Units at full inspiration (inspiratory RA950) were significantly different in nonsmoking asthmatics compared to patients with COPD and asthmatics with a smoking history. The MLD and the RA950 correlated significantly with the FEV1 in all groups and with the DL(CO) in patients with COPD and asthmatics with a smoking history but not in nonsmoking asthmatics. We concluded that the LAA in asthmatics with a smoking history indicates the presence of emphysema, but in nonsmoking asthmatics it reflects hyperinflation and nonemphysematous expiratory airflow limitation rather than emphysematous lesions.

DOI： 10.1081/JAS-100001496

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY, INC  

BACKGROUND: How leukotrienes (LTs) and IgE-mediated allergy reflect clinical features in patients with chronic obstructive pulmonary disease (COPD) remains unclear. OBJECTIVE: Our goal was to determine whether LTB4 and LTC4 would correlate with airway obstruction and whether IgE-mediated allergy would influence the generation of LTs and bronchial hyperresponsiveness in patients with COPD. METHODS: We measured the pulmonary function, methacholine bronchial hyperresponsiveness, and generation of LTB4 and LTC4 from peripheral leukocytes stimulated with calcium ionophore A23187 in relation to the presence of specific IgE antibodies against inhalant allergens. RESULTS: The leukocytes of patients with COPD generated significantly more LTB4 (with allergy, P <.001; without allergy, P <.001) and LTC4 (with allergy, P <.001; without allergy, P <.01) than the leukocytes of the control subjects. LTC4 production was significantly higher in the allergic COPD subjects than in the nonallergic COPD patients (P <.01), but the amount of LTB4 generated was not significantly different. FEV(1) significantly correlated with the level of both LTB4 (with allergy, r = -0.556, P =.0375; without allergy, r = -0.731, P =.0046) and LTC4 (with allergy, r = -0.764, P =.0043; without allergy, r = -0.526, P =.0414) generation in COPD. The log(10) of the minimum dose of methacholine was significantly higher in COPD patients without allergy than in those with allergy (P <.05). CONCLUSION: Enhanced LT generation from peripheral leukocytes is observed in patients with COPD, and the presence of specific IgE antibodies against inhalant allergens enhances LTC4 generation, bronchial hyperresponsiveness, and the relationship between LTC4 generation and airway obstruction.

DOI： 10.1067/mai.2001.112694

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 44-year-old man began to experience episodes of joint pain with erythema in his knees, elbows, shoulders, and hands in April 1996. He was diagnosed as having palindromic rheumatism. Due to the increasing frequency and severity of these episodes, he was admitted to our hospital in May 1999. Heat therapy to the affected area produced a rapid improvement in symptoms. In addition, the continued use of physical therapy during symptom-free periods tended to reduce the frequency and severity of pain attacks. We present this case and discuss treatment options in patients with palindromic rheumatism.

DOI： 10.2169/internalmedicine.40.140

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.64.203

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER-VERLAG LONDON LTD  

Despite a deepening understanding of the influence of glucocorticoids (GC) on trabecular bone, little is known about GC-induced cortical bone loss. To elucidate the mechanism of GC-induced loss of cortical bone strength with particular reference to cortical bone loss, changes in cortical density, relative cortical volume, and the Strength Strain Index (SSI) based on biomechanical analyses of the geographic distribution of cortical bone material were measured. These parameters were compared, using peripheral quantitative computed tomography (pQCT), among the following age-matched groups: 68 postmenopausal asthmatic patients receiving high-dose oral GC in addition to inhaled GC (oral GC group), 68 postmenopausal asthmatic patients receiving only inhaled GC (inhaled GC group) and 69 postmenopausal controls without asthma or GC therapy (control group). Cortical bone mineral density (BMD) was measured, relative cortical volume was obtained by dividing the cortical area by the total bone area using pQCT (Stratec XCT960), and the Strength Strain Index (SSI) was calculated in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. The number of vertebral fractures per patient correlated highly with cortical BMD, relative cortical volume and SSI values at the radius. The number of vertebral fractures per patient and the number of patients with fracture were similar between the control and inhaled GC group, both being significantly lower than those in the oral GC group. Total BMD, trabecular BMD, cortical BMD, relative cortical volume and SSI were similar between the first two, being significantly higher than in the last group. The slopes of cortical volume-density relationship, however, were identical among the three groups, indicating the persistence of cortical bone remodeling and a similar degree of calcification regardless of GC administration.

DOI： 10.1007/s001980170115

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.64.155

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Language：English   Publishing type：Research paper (scientific journal)  

Because most of the diseases to which radon (222Rn) therapy is applied are related to activated oxygen, in this study the effect of the radioactivity of radon and the thermal effect were compared under a room or a hot spring condition with the same chemical component using as the parameters the activity of superoxide dismutase (SOD), which is an oxidation inhibitor, and lipid peroxide and low density lipoprotein (LDL)-cholesterol, which are closely involved in arteriosclerosis. Results show that the SOD activity was significantly increased, and the lipid peroxide and LDL-cholesterol levels were significantly decreased on days 6 and 7 of study. The results were about 2-fold larger in the radon group than in the thermo group. This suggests that the anti-oxidation function was more enhanced by radon therapy than by thermo therapy, and suggests that radon therapy may help to prevent the causes of life style-related diseases such as arteriosclerosis. These findings are important in understanding the mechanism of diseases in which radon therapy is used as treatment, and most of which are called activated oxygen-related diseases.

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.50.973_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.50.948_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.50.318_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.50.291_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.50.935_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.50.249_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.50.289_4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MUNKSGAARD INT PUBL LTD  

Leukotrienes (LTs) are pro-inflammatory mediators that contribute to the pathophysiological features of asthma. The relationship between the amounts of LTB4 and LTC4 produced by the leukocytes of asthmatic patients on the one hand and immunoglobulin E (IgE)-mediated allergy, asthma exacerbations and bronchial hyperresponsiveness was studied. Leukocytes were obtained from peripheral blood drawn from 29 atopic and 27 nonatopic asthmatics during exacerbations and clinically controlled periods, as well as from 20 control individuals. The leukocytes were stimulated with calcium ionophore A23187 to induce LTB4 and LTC4 production. Allergy was assessed by means of specific serum IgE or by positive skin tests, whereas bronchial hyperresponsiveness was measured by methacholine challenge. The leukocytes of the asthmatics generated significantly more LTB4 (p<0.05) and LTC4 (p<0.01) than those of controls. The leukocytes of patients with atopic asthma generated significantly more LTC4 than those of patients with nonatopic asthma (p<0.01). Significantly more LTC4 was produced by leukocytes obtained during exacerbations, than by those obtained during clinically controlled periods (p<0.01). In addition, there was a significant correlation between LTB4 generation by leukocytes and the degree of bronchial hyperresponsiveness to methacholine (r=-0.792, p<0.0001). These results suggest that leukotriene C4 production by leukocytes is associated with immunoglobulin E-mediated allergy and asthma exacerbations, and further that generation of leukotriene B4 is closely related to bronchial hyperresponsiveness in patients with asthma.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

BACKGROUND: Dietary sources of alpha-linolenic acid, such as perilla seed oil, may have the capacity to inhibit the generation of leukotrienes (LTs) by leucocytes in patients with asthma, as has been reported with the consumption of other long-chain n-3 fatty acids. METHODS: The factors affecting the suppression of leukotriene (LT) C4 generation by leucocytes were examined by comparing the clinical features of patients with asthma who had been given dietary perilla seed oil (n-3 fatty acids). Group A consisted of patients in whom the leucocyte generation of LTC4 was suppressed by dietary perilla seed oil. Group B consisted of those in whom LTC4 generation was not suppressed. RESULTS: LTC4 generation by leucocytes decreased significantly in group A after 2 (p < 0.05) and 4 weeks (p < 0.05); conversely, it increased significantly in group B after 4 weeks (p < 0.05). The two study groups differed significantly in terms of LTC4 generation by leucocytes after 4 weeks of dietary supplementation (p < 0.05). Ventilatory parameters such as peak expiratory flow (PEF), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) increased significantly after 4 weeks of dietary supplementation in group A (p < 0.05). Values of PEF, FVC, FEV(1) and maximum expiratory flow at 25% of the forced vital capacity (V(25)) differed significantly between groups A and B prior to dietary supplementation. Serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol and phospholipid were significantly decreased by dietary supplementation in group A after 4 weeks. Serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL cholesterol and phospholipid differed significantly between the two study groups prior to dietary supplementation. Serum levels of triglyceride and LDL cholesterol differed significantly between the two study groups after 4 weeks of dietary supplementation. CONCLUSIONS: Dietary supplementation with perilla seed oil in selected patients with asthma suppresses the generation of LTC4 and is associated with clinical features such as respiratory function and lipometabolism.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

OBJECTIVE: to uncover any differences in the age-related and IgE-mediated pathophysiology of the airways in asthmatics. METHODS: we examined the relationship of both IgE-mediated bronchial hyperresponsiveness and the cell content of bronchoalveolar lavage fluid with a family history of asthma in 263 patients with asthma classified according to age at onset. RESULTS: bronchial hyperresponsiveness decreased significantly as age at onset increased in those without a family history. Responsiveness was significantly higher in patients who were > or = 60 years of age at onset who had a family history than in those who did not (P < 0.05). The proportion of lymphocytes in bronchoalveolar lavage fluid was significantly higher in patients between 50 and 59 years old at onset who had a family history than those who did not (P < 0.05). These results suggest that bronchial hyperresponsiveness and the proportion of bronchoalveolar lavage lymphocytes differ according to the presence or absence of a family history, a finding which is closely related to IgE-mediated allergy in elderly patients at onset. CONCLUSIONS: our findings suggest (i) the possibility of asthma induced by non-IgE-mediated allergy in elderly patients and (ii) that bronchial responsiveness is also influenced by IgE-mediated allergy and age at onset.

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.63.113

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

OBJECTIVE: The effects of perilla seed oil (n-3 fatty acids) on bronchial asthma were compared with the effects of corn oil (n-6 fatty acids) in relation to the pulmonary function and the generation of leukotriene B4 (LTB4) and C4 (LTC4) by leucocytes. METHODS AND SUBJECTS: 14 asthmatic subjects were divided randomly into two groups: one group (7 subjects) consumed perilla seed oil-rich supplementation and the other group (7 subjects) consumed corn oil-rich supplementation for 4 weeks. Generation of LTs by leucocytes and respiratory function were compared between the two groups. RESULTS: The generation of LTB4 and LTC4 by leucocytes tended to increase in subjects (N=7) with corn oil-rich supplementation, and decrease in subjects (N=7) with perilla seed oil-rich supplementation. Significant differences between the two groups were observed in the generation of LTB4 at 2 weeks (p<0.05) and LTC4 at 2 weeks (p<0.05) after dietary supplementation. Significant increases in the value of PEF (p<0.05), FVC (p<0.01), FEV(1.0) (p<0.05) and V(25) (p<0.05) were found in subjects who received perilla seed oil supplementation for 4 weeks. And significant differences in the value of FVC (p<0.05) and FEV(1.0) (p<0.05) were observed between the two groups after 4 weeks of dietary supplementation. CONCLUSION: These results suggest that perilla seed oil-rich supplementation is useful for the treatment of asthma in terms of suppression of LTB4 and LTC4 generation by leucocytes, and improvement of pulmonary function.

DOI： 10.2169/internalmedicine.39.107

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

The kind of respiratory disease, age, and areas where patients came from, were analyzed in 763 patients with COPD admitted at our hospital for last 7 years from 1992 to 1998. 1. For the last 7 years 886 patients with respiratory diseases were admitted at our hospital. Of these patients, 763 (86.1%) were those with COPD. Of the 763, 613 (80.3%) were patients with asthma, 27 with chronic bronchitis, 41 with obstructive bronchiolitis, and 87 with pulmonary emphysema. 2. The number of patients with pulmonary emphysema showed a tendency to increase. 3. The number of patients from distant areas was considerably larger (43.8% in 1997, 53.4% in 1998) compared to the number of patients from Tottori prefecture. The number of patients from Okayama, Hyogo, Osaka, Hiroshima, Yamaguchi, and Ehime prefectures was predominantly larger than the number of patients from other distant areas. 4. Regarding the age distribution of these patients, the number of patients over the age of 60 was predominantly larger than the number of patients under the age of 59: patients between the ages of 60 and 69 were more frequently observed in those coming from distant areas (outside Tottori prefecture), and those over the age of 70 in those coming from Tottori prefecture.

DOI： 10.11390/onki1962.63.65

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Language：English   Publisher：SPRINGER-VERLAG LONDON LTD  

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.49.203_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.49.968_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.49.898_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.49.911_3

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DOI： 10.15036/arerugi.49.210_3

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DOI： 10.11390/onki1962.63.16

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MUNKSGAARD INT PUBL LTD  

Chronic use of systemic glucocorticoids results in progressive bone loss and pathologic fractures. This study identified the predictive variables for bone loss and used peripheral quantitative computed tomography (pQCT) to measure changes in cortical and trabecular bone in patients receiving systemic glucocorticoid therapy of prednisone 15.4 g. Eighty-four asthmatic patients were included in the study. Vertebral fractures were diagnosed via plain spinal radiograms. pQCT was used to measure cortical and trabecular bone mineral density. Multiple regression analysis identified variables with predictive value. The cumulative dose of glucocorticoid correlated with the bone mineral density (p<0.05) and the trabecular bone density (p<0.01). Among patients > or = 65 yrs of age, the cumulative dose of glucocorticoid correlated with the occurrence of vertebral fractures (p<0.05), total bone mineral density (p<0.01) and cortical bone mineral density (p<0.01). Bone mineral density in the distal radius measured by pQCT and the vertebral bodies by axis QCT were correlated, regardless of whether systemic glucocorticoids were administered. Glucocorticoid administration not only decreases trabecular but also cortical bone mineral density. Since cortical bone provides strength and stiffness, it appears that the loss of cortical bone is responsible for the increased incidence of fracture seen in patients receiving systemic glucocorticoid therapy.

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

We observed peripheral circulation in patients suffering from peripheral neuropathy in order to quantify the effect of spa therapy on peripheral neuropathy.<br>The peripheral circulation was observed using thermography and Laser-Doppler blood flowmetry. Thirteen patients with a mean age of 71.9 years (range of 59-82) suffering from diabetic neuropathy with coldness, numbness, neuralgia in their feet or walk disturbance, and 11 patients with a mean age of 72.3 years (range of 60-84) suffering from lumbago, were examined by the methods. The blood flow, mass and velocity were measured by a Laser-Doppler blood flowmetry, after pre-loading with hot water at 36°C for 5min (hot loading), and after cold loading with cold water at 20°C for 5min. Thermographic results were analyzed quantitatively by calculating a recovery ratio as: Recovery ratio=[Total counts of thermography (Pixels) over 27°C after cold loading] ÷ [Initial counts over 27°C after hot loading]×100 (%).<br>The recovery ratio in diabetes mellitus was between 0-93.5% (mean=46.8%), whereas the recovery ratio in lumbago was between 0-91.3% (mean=41.3%). The blood flow in patients with diabetes mellitus was 1.11-5.36 (ml/min/100g tissue), (mean=2.44), the blood mass was 85-255 (mean=155), and the velocity was 0.447-0.784 (mean=0.591). The blood flow in patients with lumbago was 1.18-3.82, (mean=2.19), the blood mass was 89-195 (mean=144), and the velocity was 0.464-0.8 (mean=0.615). The recovery ratio and blood flow in patients with diabetes mellitus were correlated, r=0.62 and p<0.0002, as the recovery ratio and blood mass were correlated, r=0.59 and p<0.0001. However the blood flow and the velocity in these patients were not correlated, r=0.11. The recovery ratio and blood flow in patients with lumbago were not correlated, r=0.02, but the recovery ratio and blood mass showed some correlation, r=0.38. The recovery ratio and the velocity in these patients were correlated, r=0.64 and p<0.005. The blood flow in patients with diabetes mellitus was greater after hot loading (mean=2.89) than after cold loading (mean=2.44). The blood mass in patients with diabetes mellitus was greater after hot loading (mean=180) than after cold loading (mean=155). However, there was no significant change in the velocity after hot loading (mean=0.572) compared with the velocity after cold loading (mean=0.591).<br>It was revealed that patients with diabetes mellitus with low recovery ratios in thermography had low blood flow and blood mass in their peripheral circulation. Patients suffering from lumbago had different peripheral circulation compared with diabetes mellitus. Spa therapy was effective on diabetic peripheral neuropathy as the peripheral circulation improved with hot water at 36°C

DOI： 10.11390/onki1962.62.185

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Language：English   Publishing type：Research paper (scientific journal)  

A 57-year-old Japanese woman with well controlled rheumatoid arthritis visited our hospital with a severe bitemporal headache and marked fatigue. Based on the classification criteria by the American College of Rheumatology, she was diagnosed as having giant cell arteritis. Magnetic resonance (MR) angiography was performed, from which stenotic changes in the bilateral superficial temporal arteries were strongly suspected. Corticosteroid therapy was quickly started. The patient followed an uneventful course with no complications. Therapeutic effect was confirmed by MR angiographic findings obtained 4 weeks after the initiation of therapy.

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.62.147

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Other Link： https://jlc.jst.go.jp/DN/JALC/00086321563?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.62.121

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Other Link： https://jlc.jst.go.jp/DN/JALC/00086321525?from=CiNii

Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.48.1067_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.48.311_3

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.48.365_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.48.327_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.48.1000_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.48.281_3

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.48.1081_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.48.1069_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.48.370_2

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.62.14

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Other Link： http://search.jamas.or.jp/link/ui/1999049527

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.61.177

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Other Link： https://jlc.jst.go.jp/DN/JALC/00085231467?from=CiNii

Language：Japanese   Publishing type：Research paper (scientific journal)  

We examined age-related changes in the IgE-mediated allergic reaction in patients with late onset asthma, whose asthma first occurred at over 40 years. 1. The number of patients with a high serum IgE level (over 300 IU/ml) was larger in patients with an age of onset between 40 and (40-49 years group) and in patients older than 60 at age of onset (60-year group) than in patients with an age of onset between 50 and 59 (50-59 year group). 2. A positive RAST score to house dust mite (HDm) allergen was more frequently found in the 40-49 year group and in the 60- year group than in the 50-59 year group. Frequency of positive RAST score to HDm in the 50-59 year group was significantly lower (p < 0.01) than in early-onset asthma patients (age at onset less than 39 years). 3 Frequency of family history of asthma in the 50-59 years group was high, being equal to that of early-onset asthma patients. 4 In the 50-59 year group, the frequency of severe asthma was comparatively higher than that of the other groups. The frequency of IgE-mediated allergic reaction changed in regard to age of onset of asthma, and allergic reactions in late-onset asthma partially resembled those of early-onset asthma. These results suggest that an atopic constitution is related to the onset of bronchial asthma in the elderly.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARCEL DEKKER INC  

The release of histamine and leukotriene C4 (LTC4) from bronchoalveolar lavage (BAL) cells and peripheral blood stimulated with Ca ionophore A23187 was compared between atopic and nonatopic asthma. The proportion of basophilic cells in BAL fluid was significantly higher in atopic than in nonatopic asthma (p < 0.01); however, no significant differences were present in the other BAL cells between the two asthma types. The concentration of histamine in BAL fluid was significantly higher in younger patients (20-59 years) with atopic than in nonatopic asthma (p < 0.01). In contrast, the concentration of LTC4 was significantly higher in nonatopic than in younger patients with atopic asthma (p < 0.01). The release of histamine from BAL cells (p < 0.001) and peripheral blood (p < 0.01) was significantly larger in younger patients with atopic than in nonatopic asthma. The generation of LTC4 by BAL cells was significantly larger in nonatopic than in younger (p < 0.01) and older patients with atopic asthma (60+ years) (p < 0.05). These results suggest that both histamine and LTC4 participate in the onset mechanism of atopic asthma, and only LTC4 participates in that of nonatopic asthma.

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.47.975_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.47.1044_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.47.977_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.47.301_3

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.47.301_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.47.323_3

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.47.1096_3

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.47.326_4

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.61.20

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Other Link： https://jlc.jst.go.jp/DN/JALC/00084378804?from=CiNii

Language：Japanese   Publishing type：Research paper (scientific journal)  

To evaluate the effects of complex spa therapy (swimming training in a hot spring pool + fango therapy + inhalation of iodine salt solution) on psychological factors, three psychological examinations; CMI (Cornell Medical Index), SDS (Self-Rating Depression Scale) and CAI (Comprehensive Asthma Inventory); were given 25 patients with bronchial asthma (10 male, 15 female, mean age 60 years), and the results of these examinations were compared before and after spa therapy. 1. Physical symptoms, respiratory system and CIJ symptoms by CMI were significantly improved after spa therapy, however the improvement of psychical symptoms was not significant. 2. In SDS, 11 of 25 patients showed more than 40 points, indicating depressive state. The number of such patients decreased from 11 to 2 and the mean SDS score significantly improved from 38.7 to 34.2 after spa therapy. 3. Conditioning, suggestion, fear of expectation, frustration, flight into illness, negative attitudes towards prognosis, and decreased motivation towards therapy by CAI were significantly reduced after spa therapy, with the reduction in negative attitudes towards prognosis and decreased motivation towards therapy being relatively large. Furthermore, CAI score, which is the average of the categories in CAI, was also significantly decreased from 37.9 to 28.4 after spa therapy. These results suggested that complex spa therapy improves psychological factors in patients with bronchial asthma.

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.60.117

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Other Link： https://jlc.jst.go.jp/DN/JALC/00083812811?from=CiNii

Language：English   Publishing type：Research paper (scientific journal)  

N-3 fatty acids, such as fish oil, have been reported to have some beneficial effects in patients with bronchial asthma. The effects of dietary supplementation with perilla seed oil rich in a-linolenic acid (α-LNA), parent n-3 fatty acid, were studied in five patients with asthma. The symptoms of asthma and mean peak flow rates (PFR) both early in the morning and in the evening were improved 2 weeks after dietary supplementation and the increases in PFR were significant (P &lt
0.05). The generation of leukotriene B4(LTB4) by peripheral leukocytes stimulated with the Ca2+ionophore A23187 was significantly suppressed from 77.6 to 41.6ng/5X106cells by dietary supplementation (P&lt
0.05). The generation of leukotriene C4(LTC4) by leukocytes was also significantly suppressed from 64.0 to 38.8 ng/5x106cells after supplementation with perilla seed oil (P &lt
0.05). These results suggest that dietary supplementation with perilla seed oil is beneficial for the treatment of asthma. © 1997, Japanese Society of Allergology. All rights reserved.

DOI： 10.2332/allergolint.46.181

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Language：English   Publisher：Japanese Society of Allergology  

The incidence of a positive family history with asthma and levels of serum IgE and IgE antibodies were examined in 136 patients with asthma in relation to age at onset of the disease. The frequency of subjects with a family history of asthma ranged from 37.9 to 75.0% in all groups classified by age at onset. The frequency of patients with a high serum IgE level (≥150IU/mL) was higher (51.7-63.2%) in all groups than the frequency of patients with a low serum level (<150IU/mL). The mean level of serum IgE was significantly higher in patients with a family history than in those without a family history, in subjects between the ages of 50 and 59 years at onset (mean age 63.4 years; P<0.02) and in those over the age of 60 years at onset (74.0 years; P<0.01). The number of patients with a positive RAST score either to house dust mite (HDM), cockroach, and Candida tended to decrease as the age at onset increased. However, the frequency of positive RAST to HDM was higher in patients with a family history and who were over the age of 50 years at onset compared with those patients between the ages of 40 and 49 years at onset, although the frequency was significantly higher in patients with family history than in those without family history (P<0.02). These results suggest that IgE-mediated allergic reactions are significant not only in those patients who are younger, but also in elderly patients with asthma.

DOI： 10.2332/allergolint.46.237

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.46.262_3

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.46.207_3

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DOI： 10.15036/arerugi.46.262_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.46.842_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.46.911_3

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.46.838_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.46.843_1

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.59.133

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Other Link： https://jlc.jst.go.jp/DN/JALC/00082693930?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.59.141

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Other Link： https://jlc.jst.go.jp/DN/JALC/00082693947?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.59.201

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.59.243

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.45.911_3

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.45.250_4

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.45.259_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.45.974_2

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.59.27

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Other Link： http://search.jamas.or.jp/link/ui/1996073987

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.58.225

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Other Link： https://jlc.jst.go.jp/DN/JALC/00081808267?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.58.218

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Other Link： https://jlc.jst.go.jp/DN/JALC/00081808250?from=CiNii

Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Effects of spa therapy on psychological factors were examined in 15 patients with bronchial asthma (10 females and 5 males, mean age 55.0 years) by CMI (Cornell Medical Index), SDS (Selfrating Depression Scale), CAI (Comprehensive Asthma Inventory) and SD (Semantic Differential). The results of these psychological examinations were compared before and after spa therapy for 1-2 months.<br>1. In CMI, mean point of physical symptoms decreased from 37.7 before spa therapy to 29.7 after the therapy. Mean improvement rate of the symptoms was 73.3%. The mean improvement rate was observed in 60.0% of respiratory symptoms, 66.7% of CIJ symptoms and 46.7% in psychical symptoms.<br>2. In SDS, many patients showed more than 40 points, suggesting that they have depressive mental state. The mean point decreased from 42.9 to 40.7 by spa therapy.<br>3. In CAI, categories of mental state, extent of conditioning, suggestion, fear of expectation, dependency, frustration and flight into illness, were clearly improved by spa therapy.<br>4. It was shown in SD that character of patients changed with beneficial trend for therapy of asthma after spa therapy.<br>These results suggest that psychological disorders of patients with bronchial asthma are improved by spa therapy.

DOI： 10.11390/onki1962.58.153

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Other Link： https://jlc.jst.go.jp/DN/JALC/00081495016?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.58.180

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Other Link： https://jlc.jst.go.jp/DN/JALC/00081495047?from=CiNii

Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.44.966_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.44.1015_2

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.57.183

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Other Link： https://jlc.jst.go.jp/DN/JALC/00080461272?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.57.142

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Other Link： https://jlc.jst.go.jp/DN/JALC/00080209478?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.57.199

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Other Link： https://jlc.jst.go.jp/DN/JALC/00080461289?from=CiNii

Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.43.378_4

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DOI： 10.15036/arerugi.43.364_3

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DOI： 10.15036/arerugi.43.1044_3

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DOI： 10.15036/arerugi.43.1044_4

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DOI： 10.15036/arerugi.43.995_1

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Language：English   Publishing type：Research paper (scientific journal)  

Immunoallergological studies were carried out to clarify the differences between 24 patients with drug-induced asthma (DIA) and 240 with non-drug-induced asthma (non-DIA). The mean values of age, skin reaction to Candida albicans (C. albicans), serum IgE levels, specific IgE antibodies to house dust (HD) and C. albicans, bronchial sensitivity and leukotriene B4 (LTB4) synthesis from peripheral venous blood in patients with DIA were not significantly different from those in patients with non-DIA. In contrast, the frequency of positive skin reaction to HD and histamine release from peripheral basophils by anti-IgE were significantly lower in DIA than in non-DIA. These results agree with the reports that DIA was often observed in non-atopic asthma. But, the mean value of serum IgE was very high in DIA as well as in non-DIA. This result suggests that IgE mediated reaction in DIA is important. Furthermore, the proportion of neutrophils in bronchoalveolar lavage fluid (BALF) was significantly lower in DIA than in non-DIA. Our findings suggest that a decrease of intrapulmonary neutrophils might play an important role in the pathophysiology of DIA.

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The effects of long-term glucocorticoid therapy on chemical mediator and cellular reaction in the airways were examined in 69 patients with bronchial asthma. The histamine release induced by Ca ionophore A23187 from cells in the bronchoalveolar lavage (BAL) fluid of atopic asthmatics was significantly lower in the subgroup with steroid-dependent intractable asthma (SDIA) than in non-SDIA patients (p < 0.05). In contrast, histamine release in nonatopic SDIA patients did not differ from nonatopic non-SDIA patients. The release of leukotriene C4 (LTC4) was significantly lower in atopic patients with SDIA (p < 0.02). However, there was no significant difference in LTC4 release between nonatopic patients with SDIA and without SDIA. The proportion of BAL lymphocytes was significantly lower in atopic patients with SDIA than in those without it (p < 0.05), although there was no significant difference between the nonatopic patients with and without SDIA. These results show that glucocorticoids affect humoral and cellular events in the airways of atopic asthmatics more than in those of nonatopic asthmatics.

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Cell-mediated immunity was examined in 45 patients with bronchial asthma by observing the delayed cutaneous reaction to purified protein derivative (PPD) and Candida albicans (C. albicans). The delayed skin reaction to PPD showed a decrease with age starting between 50 and 59 years old. The delayed reaction to PPD decreased more prominently with aging, being significantly depressed in the patients aged over 70 years than in those aged between 30 and 49 years (induration, p < 0.02; flare, p < 0.01). The C. albicans-induced skin reaction was significantly lower in the patients aged over 70 years than in those between 60 and 69 years old (induration, p < 0.01; flare, p < 0.05). The delayed skin reaction to PPD and C. albicans was significantly depressed in the patients with a serum IgE level over 1001 IU/ml. Delayed skin reaction to PPD and C. albicans was more depressed with aging and an elevated serum IgE, and the age (50-59 years) at the initiation of depression in the PPD-induced delayed skin reaction was younger than that (over 70 years) in the C. albicans-induced reaction.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Effects of long-term glucocorticoid therapy on airway inflammatory cells were examined in 40 patients with bronchial asthma. 1. The dose of glucocorticoids required by asthmatic patients tended to increase and the level of serum cortisol tended to decrease with prolongation of the period of glucocorticoid therapy. 2. The proportion and number of lymphocytes in bronchoalveolar lavage (BAL) fluid decreased with prolongation of the period of glucocorticoid therapy. The proportion of BAL lymphocytes in asthmatic patients treated with glucocorticoids for more than 5 years was significantly lower than that in those treated for less than 4.9 years. 3. The proportion and number of BAL neutrophils increased with prolongation of the period of glucocorticoid therapy and the proportion of BAL neutrophils in patients treated with glucocorticoids for more than 10 years was significantly higher compared with those treated for less than 9.9 years. These findings indicate that long-term glucocorticoid therapy induces changes in airway inflammatory cell profiles, with a decrease in the number of lymphocytes and increase in the number of neutrophils.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Fifty patients with bronchial asthma were divided into four groups according to the amount of expectoration per day: 0-24, 25-49, 50-99 and 100+ ml/day. Clinical features of patients with mucus hypersecretion (more than 50 ml/day of expectoration) were evaluated by age, severity of disease, cellular composition of bronchoalveolar lavage (BAL) fluid, and ventilatory function. 1. The proportion of patients with steroid-dependent intractable asthma (SDIA) in each group increased with increase in mucus hypersecretion. 2. Many of the patients with mucus hypersecretion (more than 50 ml/day) were over the age of 40. 3. The proportion of BAL eosinophils was significantly higher in patients with hypersecretion (more than 50 ml/day) than in those with expectoration of less than 49 ml/day. There was a significant correlation between the proportion of BAL eosinophils and the amount of expectoration per day (r = 0.48, p < 0.05). Proportions of lymphocytes and neutrophils in the BAL fluid were not related to the amount of expectoration per day. 4. There was no significant correlation between the amount of expectoration per day and ventilatory function in patients with asthma in this study.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

The correlation between proportions of cells in bronchoalveolar lavage (BAL) fluid and ventilatory function was examined in 52 patients with asthma. 1. There was no significant correlation between the proportion of BAL lymphocytes and ventilatory function. 2. The proportion of BAL eosinophils correlated to a certain extent with ventilatory function: the values of %MMF, %V50 and %V25 were lower in patients with BAL eosinophils of 10-19.9% than in those with BAL eosinophils below 4.9%, and %V25 value was significantly lower in patients with a high proportion of BAL eosinophils (10-19.9%) compared with those with a low proportion of BAL eosinophils (0-4.9%). However, ventilatory function was not decreased in patients with BAL eosinophils of more than 20%. 3. The values of ventilatory parameters showed a tendency to decrease with increase in BAL neutrophils. The values of all parameters of obstructive ventilatory dysfunction were significantly lower in patients with BAL neutrophils of > 10% than in those with BAL neutrophils < 4.9%. A significant difference between patients with BAL neutrophils > 10% and < 9.9% was found in values of %V50 and %V25, and the values of %V50 and %V25 were significantly lower in patients with a high proportion of BAL neutrophils (> 10%) than in those with BAL neutrophils < 9.9%. These results suggest that the proportion of BAL eosinophils is to a certain extent related to ventilatory function of asthma patients and that the increase in proportion of BAL neutrophils is closely related to a decrease in values of obstructive ventilatory parameters.

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The clinical effects of spa therapy (swimming training in a hot spring pool+inhalation of iodine salt solution+fango therapy) were examined in 52 patients with steroid-dependent intractable asthma (SDIA). Clinical effects were found in 36 of the 52 (69.2%) patients with SDIA. The efficacy was higher in the patients between the ages of 41 and 50 (87.5%) and between 51 and 60 (84.2%) than in those in the other age groups. Regarding clinical asthma types, the efficacy of spa therapy was higher in patients with type Ia-2 (83.4%), type Ib (77.8%) and type II (80.0%) than in those with type Ia-1 (54.2%). Efficacy seemed to be related to airway inflammation: the proportion of neutrophils and eosinophils in bronchoalveolar lavage (BAL) fluid was higher in patients with marked and moderate improvement compared with those with slight and no improvement. Ventilatory function was improved by complex spa therapy. %MMF and %V25 values increased by more than 20% after therapy in patients with type Ia-2, Ib and II asthma. Bronchial hyperreactivity to methacholine was suppressed after therapy. Any decreased function of the adrenocortical glands expressed by low serum cortisol levels improved after therapy, accompanied by a reduction in the dose of glucocorticoids necessary to control asthma attacks.

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The clinical features of four asthma types, Ia-1 (bronchospasm with 0-49 ml/day of expectoration), Ia-2 (with 50-99 ml/day), Ib (over 100 ml/day), and II (bronchiolar obstruction), as classified by the clinical symptoms, were compared in 119 patients with bronchial asthma. The age of onset characteristic symptoms of each asthma type was in the 20's in types Ia-1 and Ia-2, in the 30's in type Ib, and in the 40's in type II patients. A significant increase in the number of neutrophils in bronchoalveolar lavage (BAL) fluid was found in type II patients. The proportion of BAL eosinophils was significantly higher in types Ia-2 and Ib asthma patients compared with that in type Ia-1 patients. The BAL eosinophil count was significantly higher in type Ib than in type Ia-2 patients. The FEV1.0% and %V25 values were significantly lower in patients with type II asthma than in the patients with the other asthma types. Steroid-dependent intractable asthma (SDIA) was more often observed in patients with type Ib or type II asthma.

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Asthma was classified into three types according to clinical symptoms (clinical diagnosis, C.D.): Ia. simple bronchoconstriction type (further divided into two subtypes, type Ia-1 with 0-49 ml/day of expectoration and type 1a-2 with 50-99 ml/day); Ib. bronchoconstriction + hypersecretion type, and II. bronchiolar obstruction type. Asthma was also classified by a score related to clinical findings and examinations (score diagnosis, S.D.). The clinical features of each type of asthma according to the two classifications methods were compared. Type 1a-2 and 1b patients (C.D.) were characterized by mucus hypersecretion (more than 50 ml/day) and eosinophilia in the bronchoalveolar lavage (BAL) fluid. The characteristic findings for type II asthmatics (C.D.) were a lower %V25 value (less than 10%) and an increased proportion of neutrophils (more than 20%) in the BAL fluid. All of the patients classified as types 1a-1, Ib, and II by clinical diagnosis were evaluated as having the same types of asthma by score diagnosis. Patients with type Ia-2 evaluated by clinical diagnosis were classified as type Ib by score diagnosis, since these two types had similar pathophysiological features represented by the increased proportion of eosinophils in the BAL fluid.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Asthma was classified into four types, Ia-1 (bronchospasm with 0-49 ml/day of expectoration), Ia-2 (with 5-99 ml/day), Ib (over 100 ml/day) and II (bronchiolar obstruction), according to clinical symptoms. Characteristics of airway responses in each clinical asthma type were compared between 25 elderly (mean age, 65.2 years) and 30 younger subjects (mean age, 44.9 years) with bronchial asthma, by observing ventilatory function and cellular composition in bronchoalveolar lavage (BAL) fluid. 1. In patients with types 1a-2 and Ib, the %V25 value was significantly lower in the elderly subjects than in the younger subjects. 2. Comparing the values of ventilatory parameters of type Ia-1 cases with other asthma types, %V25 value was lower in other asthma types than in type Ia-1 in the elderly. All ventilatory parameters examined were generally lower in type II cases than in other asthma types in the elderly, but this difference was not significant. In contract, in the younger subjects, the values of %MMF, %V50 and %V25 were significantly lower in type II cases than in other asthma types. 3. The proportion of neutrophils in bronchoalveolar lavage (BAL) fluid was higher in the younger patients with type II than in the elderly patients with the same type, although there was no significant difference between older and younger subjects. The proportion of BAL eosinophils in patients with type Ib was significantly higher in younger subjects than in elderly subjects. These results indicate that airway responses which are characteristic of each asthma type are stronger in younger patients than in elderly patients.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Thirty patients with atopic asthma in whose asthma IgE-mediated allergic reaction participates, were selected for this study. They were divided into three age groups: elderly patients aged 60 and over, middle-aged patients between the ages of 40 and 59, and young patients between 20 and 39, to clarify the effects of aging on the mechanism of onset of asthma. In the cellular composition of bronchoalveolar lavage (BAL) fluid, the proportion of BAL lymphocytes was increased in elderly patients, and the proportion of BAL eosinophils was increased in young patients, although there was no statistically significant difference between the proportions of these cells in the three age groups. The proportion of BAL basophilic cells (basophils and mast cells) was significantly lower in elderly patients than in young patients (p < 0.05). The release of histamine from BAL cells was significantly lower in elderly patients than in middle-aged patients (p < 0.05) and young patients (p < 0.02). There was, however, no significant difference between the release of leukotrienes C4 (LTC4) and B4 (LTB4) in the three age groups. The release of histamine, LTC4 and LTB4 from peripheral leucocytes was not significantly different between the three age groups. Finally, Bronchial reactivity to methacholine showed a tendency to decrease with aging.

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A relationship of cellular composition in the airways and the release of chemical mediators from the cells to bronchial hyperresponsiveness was examined in two age-matched asthma groups: 15 atopic and 15 nonatopic patients. 1. A significant correlation between the proportion of eosinophils in bronchoalveolar lavage (BAL) fluid and bronchial reactivity (BR) was found in patients with atopic and nonatopic asthma. The proportion of the cells (combined eosinophils and neutrophils) in BAL fluid was closely correlated with BR in patients with atopic asthma, but not in those with nonatopic asthma. There was no correlation between the proportion of BAL neutrophils and BR in the two asthma groups. 2. There was a significant correlation between histamine release from BAL cells and BR in patients with atopic asthma. In contrast, LTC4 release from BAL cells was significantly corrected with BR in patients with nonatopic asthma. The results suggest that the humoral and cellular components in the airways, that participate in bronchial hyperresponsiveness, are different between patients with atopic and nonatopic asthma.

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Language：English   Publisher：The Japan Society for Clinical Immunology  

Association of age and serum IgE levels with pathophysiology of asthma was examined in 64 patients with asthma. Positive RAST scores of 2+ or more to inhaled allergens were significantly higher in patients with high serum IgE than in those with low serum IgE in 4059 year-olds. The proportion of BAL lymphocytes was significantly higher in patients over age 60 with high serum IgE compared with those between 20 and 39 and between 40 and 59 with either high or low serum IgE. The release of histamine or leukotriene C₄, from leucocytes was significantly higher in patients with high serum IgE than in those with low serum IgE in 20-39 (both histamine and LTC₄) and over 60 year-olds (histamine).

DOI： 10.2177/jsci.16.44

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Publisher：The Japan Society for Clinical Immunology  

The levels of histamine and leukotriene C₄ (LTC₄) in bronchoalveolar lavage (BAL) fluid and the release of these mediators from BAL cells stimulated by Ca ionophore A 23187 were examined in 22 athmatic subjects. In BAL fluid, histamine was detectable in 9 (40.9%) and LTC₄, was detectable in 10 (45.5%) of the 22 asthma patients. BAL cells from patients with detectable histamine (DH), many of whom were evaluated as atopic, released more histamine and less LTC₄ than those of patients without DH. In contrast, BAL cells from patients with detectable LTC₄ (DL), many of whom were assessed as nonatopic, released more LTC₄ and less histamine than those of patients without DL. These results suggest that histamine and LTC₄ levels differ in relation to the IgE-mediated allergic reaction.

DOI： 10.2177/jsci.16.99

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The proportion of inflammatory cells in bronchoalveolar lavage (BAL) fluid and the release of chemical mediators from BAL and peripheral blood cells were examined in 40 patients with steroid-dependent intractable asthma (SDIA) to clarify the effects of a long-term glucocorticoid regimen on these cells. The proportion of BAL lymphocytes was significantly reduced (p < 0.01) and the proportion of BAL neutrophils was significantly increased (p < 0.01) in SDIA patients compared with non-SDIA patients. The proportion of basophilic cells (mast cells and basophils) in BAL fluid was significantly lower in SDIA patients compared to non-SDIA patients (p < 0.02). The values of six ventilatory parameters were significantly lower in SDIA patients with a high proportion of BAL neutrophils (more than 10%) compared with the values in non-SDIA patients. The release of histamine and leukotriene C4 (LTC4) from the BAL cells of patients with atopic asthma was significantly reduced in SDIA patients compared with non-SDIA patients (p < 0.05). These results show that the changes in the proportion of BAL cells are observed in patients with SDIA, and these changes are related to suppressed ventilatory function and a reduction in the release of histamine and LTC4 from BAL cells.

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The effects of glucocorticoids on the proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid in relation to humoral and cellular immunity were studied in 56 patients with steroid-dependent intractable asthma. To analyze the mechanism responsible for reduced numbers of BAL lymphocytes, we divided the subjects into 4 groups according to their BAL lymphocyte proportions: 0-4.9%, 5.0-9.9%, 10.0-14.9%, and 15.0-20.0%. Serum IgG levels and the peripheral lymphocyte count were significantly reduced in patients with a low proportion of BAL lymphocytes (less than 9.9%) than in those with more than 10% BAL lymphocytes. Delayed cutaneous reactivity to purified protein derivative was suppressed in patients with a low proportion of BAL lymphocytes (less than 4.9%). The mean proportion of BAL neutrophils tended to increase as the proportion of BAL lymphocytes decreased. These results show that the reduction in BAL lymphocytes produced by glucocorticoids is associated with suppressed humoral and cellular immunity, and that under such conditions the proportion of BAL neutrophils increases.

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Mucus hypersecretion was clinically analyzed in 46 adult patients with bronchial asthma, including 22 with steroid-dependent intractable asthma (SDIA). A large amount of expectoration, over 50 ml/day, was observed in 16 of these patients (34.8%), of whom 12 (75.0%) had SDIA and 13 (81.3%) were women. The mean amount of expectoration increased with increasing patient age, although no significant difference was found among the six age groups. A large amount of expectoration (over 50 ml/day) was clearly correlated with an increased proportion of eosinophils in bronchoalveolar lavage (BAL) fluid. The proportion of BAL eosinophils was significantly higher in patients with expectoration between 50 and 99 ml/day (p < 0.05) and over 100 ml/day (p < 0.01) than in patients whose expectoration volume was between 30 and 49 ml/day. These results show that in bronchial asthma patients, mucus hypersecretion is more often observed clinically in those with SDIA and in women, and that this hypersecretion is closely correlated with BAL eosinophilia, which is a feature of the pathophysiological changes that occur in the airways of these patients.

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The effects of long-term glucocorticoid therapy on airway inflammation were examined in 84 asthma patients. The proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid was significantly decreased in patients with steroid-dependent intractable asthma (SDIA) compared to results in non-SDIA patients, while BAL neutrophils were significantly increased in SDIA patients compared to results in non-SDIA patients. Regarding age, in patients under the age of 69 (except those between 30 and 39), BAL lymphocyte number was significantly decreased in SDIA compared with non-SDIA subjects, and in patients between 50 and 69, BAL neutrophils were significantly increased in SDIA compared with non-SDIA subjects. The number of BAL lymphocytes was significantly lower in patients with serum cortisol levels of less than 5.0 micrograms/dl than in those with levels of more than 5.1 micrograms/dl. BAL lymphocyte number was also significantly lower in patients who had received glucocorticoid therapy for more than 6 years than in those who had received such therapy for 2 years. These results show that long-term glucocorticoid therapy decreases the number of lymphocytes and increases neutrophil numbers in the airways.

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.56.113

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.56.79

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.56.135

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.56.211

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.56.195

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.56.203

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Other Link： https://jlc.jst.go.jp/DN/JALC/00079760911?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.56.87

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.56.143

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.42.1322_1

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.42.1470_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.42.477_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.42.410_2

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Bronchial asthma was classified by the pathophysiology and by the mechanism of onset of the disease. Forty asthmatics who had serum IgE levels lower than 200 IU/ml were evaluated by two classification methods. 1. In asthma classified by a score based on clinical findings and examinations, the characteristics of the findings and examination results were compared among three asthma types, i.e., Ia. simple broncho-constriction type, Ib. bronchoconstriction+hypersecretion type, and II. bronchiolar obstruction type. Type Ib patients, in addition to manifesting hypersecretion, had a significantly higher proportion of eosinophils in the bronchoalveolar lavage (BAL) fluid compared to other asthma types. Significantly decreased values for ventilatory parameters and an increased proportion of BAL neutrophils were found in type II compared with other asthma types. 2. In a new classification by mechanism of onset, asthma was classified into three types according to the degree of participation of IgE-mediated reactions associated with specific IgE antibodies and serum levels of total IgE: asthma induced by definite IgE-mediated reaction (atopic asthma), possible IgE-mediated reactions (asthma), and asthma induced by non-IgE-mediated reaction (asthma syndrome).

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Pathophysiological changes in the airways with aging were examined in 78 patients with bronchial asthma. The FEV1.0% values in patients over the age of 71, and the %MMF, %V50 and %V25 values in those over 51 were significantly lower than those of patients between the ages of 10 and 30. The frequency of lymphocytes in bronchoalveolar lavage (BAL) fluid was significantly higher in patients aged between 61 and 70 than in those aged between 41 and 50 (p < 0.05). The frequency of each clinical asthma type changed with aging; the number of patients with simple bronchoconstriction type (type Ia) decreased with increasing age in patients under the age of 60, and the number of those with bronchiolar obstruction type (type II) increased with aging. The frequency of patients with bronchoconstriction+hypersecretion type (type Ib) showed a peak between the ages of 51 and 60. Bronchial reactivity to methacholine showed a tendency to decrease with aging. The release of histamine from leucocytes induced by Ca ionophore A23187 was significantly higher in patients between the ages of 10 and 30 than in those between the ages of 51 and 60 (p < 0.05) and between 61 and 70 (p < 0.01).

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A 58-year-old farmer was admitted to our hospital because of repeated episodes of anaphylaxis. He had experienced 12 episodes of anaphylactic shock over the previous 17 years. These attacks included three episodes of bee sting. In general, the episodes occurred during farm work (exercise) and within two hours of eating cake in the afternoon. Because an immediate skin reaction to wheat flour was highly positive, a diagnosis of wheat allergy was considered. These findings suggested that his illness was consistent with food-dependent exercise-induced anaphylaxis.

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Twenty-one patients with atopic asthma were classified into three types according to their symptoms (clinical diagnosis): Ia, simple bronchoconstriction; Ib, bronchoconstriction + hypersecretion; and II, bronchiolar obstruction, and this classification was compared with a classification made according to clinical findings and examinations (score diagnosis). Type Ib asthma was characterized by the increased incidence of eosinophils in bronchoalveolar lavage fluid (BALF), while type II was characterized by ventilatory dysfunction in small airways and the increased incidence of neutrophils in BALF. Four patients, whose expectoration was between 50 and 99ml/day, of the 12 with type Ia assessed by clinical diagnosis were evaluated as type Ib by score diagnosis. One patient with type II by clinical diagnosis was assessed as questionable type II by score diagnosis. In the other 16 patients, the clinical and score diagnoses were the same.

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The improvement of ventilatory function by spa therapy was examined in 37 patients with steroid-dependent intractable asthma (SDIA) in relation to clinical asthma types. All subjects had been on long-term corticosteroid therapy before spa therapy. Spa therapy was found to improve the values of ventilatory parameters. The percent improvement in all subjects was +4.1% in %FVC, +8.9% in FEV1.0%, +9.8% in %PEFR, +22.0% in %MMF, +19.7% in %V50 and +28.2% in %V25, respectively. Relating to clinical asthma types, moderate improvement in %MMF and %V25 from 16.7% to 16.9% was observed in type Ia cases, and marked increase in %MMF, %V50 and %V25 was observed from 42.2% to 43.2% in type Ib cases. However, no significant increase was found in these parameters of types Ia or Ib after spa therapy. In patients with type II, a significant increase was shown in %V50 (p less than 0.05) and %V25 (p less than 0.01) after spa therapy. The results show that spa therapy improves the condition of small airways disorder in patients with SDIA.

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Delayed cutaneous reactivity to Candida albicans (C. albicans) and PPD (purified protein derivative) was examined in 52 patients with bronchial asthma in relation to the production of specific IgG4 antibodies against the antigen. 1. The frequency of a positive, immediate skin reaction to C. albicans was similar among the five age groups, ranging from 60.0% to 66.7%. 2. The incidence of a positive delayed skin reaction to C. albicans was lower in patients between the ages of 10 and 30 and tended to decrease with aging in the patients over the age of 51. 3. A delayed skin reaction to PPD was positive in patients between 31 and 50 with a higher incidence; this incidence decreased in patients over age 51. 4. The level of C. albicans-specific IgG4 antibodies was significantly higher (26.7 u/ml) in patients with a negative delayed skin reaction to the antigen than in those with a positive reaction (5.9 u/ml) (p less than 0.001). There was no correlation between delayed skin reaction to PPD and production of specific IgG4 antibodies.

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Asthma classification by clinical symptoms and signs (clinical diagnosis) was compared with the classification by score calculated from clinical findings and examinations (score diagnosis) in 25 patients with bronchial asthma. 1. Ten subjects classified as Ia (simple bronchoconstriction type) by clinical diagnosis were divided into 6 cases with expectoration of less than 49 ml a day and 4 cases with expectoration of between 50 and 99 ml. The level of serum IgE and number of eosinophils in BALF were significantly higher in the latter cases than in the former cases. The cases whose expectoration was from 50 to 99 ml a day were classified as Ib (bronchoconstriction with hypersecretion type) by score diagnosis. 2. The six subjects who were classified as type Ib by clinical diagnosis were also evaluated as type Ib by score diagnosis. 3. Nine of the 10 subjects classified as type II by clinical diagnosis were evaluated as type II by score diagnosis. One case, whose score was under 12 points, was evaluated as questionable type II by score diagnosis.

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The cellular composition of bronchoalveolar lavage (BAL) fluid was observed in 28 patients with house dust mite-sensitive asthma. The proportion of neutrophils in the BAL fluid was significantly higher in the patients between the ages of 50 and 59 and those over 60 than in the patients younger than age 39. There was a significant difference in the number of neutrophils in patients aged 30-39 years and in those over 40 at the onset of disease. The cellular composition varied among the three types of asthma; the mean percentage of cells in the BAL fluid was 1.1% neutrophils and 21.3% eosinophils in type Ia (simple bronchoconstriction), 9.1% neutrophils and 23.0% eosinophils in type Ib (bronchoconstriction + hypersecretion), and 34.4% neutrophils and 12.0% eosinophils in type II (bronchiolar obstruction). The results suggested that an increased frequency of both neutrophils and eosinophils correlates with the mechanism of hypersecretion, and that a marked increase in the proportion of neutrophils is involved in bronchiolar obstruction.

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Language：English   Publisher：The Japan Society for Clinical Immunology  

The release of histamine induced by C. albicans was significantly higher in asthmatics aged 21-30 yr, 41-50 yr and 61+ years old compared with the age-matched groups of healthy subjects. The level of C. albicans specific IgG was significantly higher in asthmatics aged 41-50 years old compared with age-matched group of healthy subjects. No significant difference was found among any age groups of healthy and asthmatic subjects. The increased level of C. albicans specific IgG seemed not to be of significance in the pathogenesis of asthma.

DOI： 10.2177/jsci.15.162

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Language：English   Publisher：The Japan Society for Clinical Immunology  

A correlation between serum levels of IgE and IgG, was examined in 79 patients with bronchial asthma. High levels of IgG₄ were not always correlated to high levels of IgE in all subjects with asthma. IgG₄ levels tended to increase as IgE levels increased in patients over age 60, but not in those under age 59. The results show that serum IgG₄ levels are associated with serum IgE levels in patients over age 60 and are related to patient age in all subjects with asthma.

DOI： 10.2177/jsci.15.459

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Specific IgG4 antibodies against Candida albicans in sera were measured in 76 asthmatics. The increased level of specific IgG4 was found in cases 10-40 years old sensitive to house dust mite and/or Candida albicans, in cases with steroid-dependent intractable asthma (SDIA) and in elderly cases. The frequency of SDIA was the highest in cases 41 to 60 years old with higher frequency of increased IgG4 antibodies. The results show that specific IgG4 increases in relation to IgE-mediated immune response, long-term steroid therapy, and aging. All of these conditions may induce depressed cell-mediated immunity.

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.55.185

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.55.82

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Other Link： https://jlc.jst.go.jp/DN/JALC/00078367616?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.55.127

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Other Link： https://jlc.jst.go.jp/DN/JALC/00078715721?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.55.134

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Other Link： https://jlc.jst.go.jp/DN/JALC/00078715738?from=CiNii

Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.55.77

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki1962.55.179

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Other Link： https://jlc.jst.go.jp/DN/JALC/00078902435?from=CiNii

Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.41.313_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.41.1100_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.41.293_3

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.41.1065_1

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Serum levels of total IgE, specific IgE, IgG and IgG4 against house dust mite were measured in mite-sensitive asthma patients receiving immunotherapy with house dust. Serum levels of total IgE, mite specific IgE and IgG did not significantly change during the course of hyposensitization. Increased levels of mite specific IgG4 were observed in patients during immunotherapy. The increase in specific IgG4 was dependent on the total dose of house dust administered in both children (r = 0.636, p less than 0.001) and adults (r = 0.629, p less than 0.01). However, the increase of specific IgG4 in adults was not as apparent as in children. These results might suggest that mite specific IgG4 is a useful immunological marker in the immunotherapy for allergic asthma, and that IgG4 antibody acts as a blocking antibody in atopic bronchial asthma.

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Language：Japanese   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

Annual changes in age, age at onset, incidence of cases with steroiddependent intractable asthma, clinical asthma types and clinical efficacy rate were examined in 256 patients with chronic respiratory diseases, especially in 203 cases with bronchial asthma, admitted to Misasa Branch Hospital from 1982 to 1989.<br>1. A number of patients with respiratory diseases as well as asthmatics admitted each year, having spa therapy, increased from early year (1982) to later year (1989).<br>2. A number in cases with 40 year or over of age (also with 60 year or over of age) and cases with 40 year or over of age at onset showed a tendency to increase in later three years (1987-1989). A decreased frequency of cases with steroid-dependent asthma and of cases with type II (bronchiolar obstruction type) was observed in the later three years.<br>3. The clinical efficacy of spa therapy for bronchial asthma was Niger in the later three years than in early three years (1982-1984).

DOI： 10.11390/onki1962.54.161

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.40.970_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.40.380_4

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Language：English   Publishing type：Research paper (scientific journal)  

To assess the transforming capability of the c-Jun protein, we introduced the chicken c-jun proto-oncogene into a replication competent avian retroviral expression vector (RCAS). Viral Jun efficiently transformed chicken embryo fibroblasts (CEFs) when expressed from this vector. Overexpression of c-Jun leads to transformation of CEFs with an efficiency that is 15- to 25-fold less than that seen for v-Jun, suggesting that v-Jun contains structural features that increase its oncogenic potential relative to c-Jun. There are four structural differences between v-Jun and c-Jun. To determine the relative contribution that each of these structural differences between v-Jun and c-Jun has on oncogenic activity, several deletion and substitution mutants were constructed. Each of these mutants was expressed in CEF and assayed for transformation by focus formation. Analysis of the results reveals that deletion of a region of 27 amino acids near the amino terminus of c-Jun and deletion of 3'-untranslated sequences are critical in activating the full oncogenic potential of Jun.

PubMed

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In order to understand the mechanism of oncogenic activation, we have analyzed the c-raf-1 gene from the GL-5-JCK human glioblastoma, which underwent rearrangement during transfection experiments. Nucleotide sequencing of cDNA clones derived from the 2.5 kb raf-mRNA, which is a major transcript of raf in NIH3T3 cells transformed with GL-5-JCK DNA, revealed that this mRNA contains sequences derived from the human c-raf-1 gene and the human lipocortin II gene. Translation of the 2.5 kb raf-mRNA predicted a fusion protein consisting of 16 amino-terminal amino acid residues of the lipocortin II and 370 carboxy-terminal amino acid residues of the c-raf-1 protein which contains the kinase domain. Expression of the lipocortin II-raf cDNA using the murine sarcoma virus long terminal repeat as promoter resulted in the transformation of NIH3T3 cells.

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

We found and characterized a type D retrovirus produced in a human lymphoblastoid cell line of B-cell lineage. The amino acid sequence of the N-terminal region of the purified major structural protein (PVTRSQGQVSSNTTGRASPHPDTHTIPE) revealed no high homology with any of the known retroviral amino acid sequences. We have cloned cDNA and the proviral genome integrated in the retrovirus-producing cells, and determined the complete nucleotide sequence and gene structures of the genome. The provirus genome is 8785 bp long and has the structure of LTR-gag-prt-pol-eny-LTR. The nucleotide sequences of the long terminal repeat (LTR) region and a part of the pol gene were closely related to the available sequences of squirrel monkey retrovirus (SMRV), and we designated this virus SMRVHLB' abbreviated as SMRV-H. The primer (tRNA(Lys)1,2)-binding sequence of SMRV-H (TGGCGCCCAGGACGTGGGGCTCGA) has a GG insertion, which is different from that of SMRV. The transmembrane protein of the 3' terminal region of env gene contains an amino acid sequence of an immunosuppressive peptide (EVVLQNRRGLDLLTAEQGGICLALQERCCFYANKS), in which R is unique in SMRV-H. The core sequence of the glucocorticoid regulatory element is found upstream of the two 42-bp imperfect repeats in the LTR. Sequences partially homologous to those of the rat IgE-binding protein gene are in gag and pol genes.