Language：Japanese   Publisher：(一社)日本内分泌学会  

49歳女。左副腎腫瘍を主訴とした。腹部単純・造影CT、腹部エコー、MRI各画像所見で左副腎部に嚢胞性病変を認めた。副腎インシデンタローマと診断され、定期的なフォローはされていなかったが、病変は7年前の44mm大から63mm大となっていた。腹腔鏡下左副腎腫瘍摘出術を行い、病理所見より異所性甲状腺腫と診断した。甲状腺エコーやI-131取込みシンチグラフィーでは悪性を疑う所見は認めなかった。なお、副腎発生の異所性甲状腺腫の報告は今までに約10例で、極めて稀である。

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DOI： 10.18926/bgeou/54229

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Language：Japanese   Publisher：(一社)日本学校保健学会  

養護教諭が外傷(頭部外傷、顔面外傷、四肢外傷、胸・腹部外傷)救急処置過程において感じている困難などを明らかにすることを目的に、B県の全公立学校の養護教諭を対象にアンケート調査を行い、143名(養護教諭経験年数平均22.3±11.6年)より有効回答を得た。その結果、養護教諭は外傷の救急処置過程において、緊急度・重症度を判断するためのポイントが何であるか、また、その所見をとるための技術に対する自信が低く、困難を感じていることが分かった。

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DOI： 10.18926/CTED/53243

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30歳男。口渇を主訴に前医受診した。血漿浸透圧が尿浸透圧より高値を示し、血中AVP分泌が低下していた。下垂体MRIのT1強調像で後葉の高信号消失と下垂体茎の腫大を認められた。高張食塩水負荷検査においてもAVP分泌は抑制されたままであり、DDAVP負荷検査で尿量減少と血漿浸透圧の上昇がみられたことから中枢性尿崩症と診断され、DDAVP治療を開始された。著明な眼瞼黄色局面の皮膚所見からErdheim-Chester病(ECD)が疑われ、精査目的で当院に紹介された。全身CTで右第5肋骨と両側骨盤に骨融解像を認めた。眼瞼黄色局面の皮膚生検を行ったところ、CD68陽性の泡沫細胞・巨細胞浸潤が認められ、ECDと診断した。

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A 42-year-old female with body weight loss, finger tremors and ocular discomfort was diagnosed with Graves' disease complicated with ophthalmopathy. Thiamazole therapy rapidly improved her hyperthyroidism. However, she was admitted to our hospital because her eye symptoms acutely deteriorated over a period of two weeks. She had ocular immotility, exposure keratitis, conjunctival edema, severe proptosis and visual impairment with a high titer of serum thyroid-stimulating antibody (TSAb). Methylprednisolone pulse therapy at a dose of 500 mg/day improved her eye symptoms. Although the mechanism of the progression of Graves' ophthalmopathy has not yet been elucidated, special attention should be paid to the occurrence of ophthalmopathy even after the initiation of thiamazole therapy.

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小学生を対象に身体症状の調査を行った結果、「腹痛」、「だるい」、「頭痛」の訴えの頻度が高く、低学年では特に多くの身体症状と悩みの関連が見られた。心的背景が身体症状や睡眠状態に影響を与えていたが、その関連には性別や発達段階による特徴があり、低学年では「腹痛」、「下痢」などの消化器症状が、高学年では「いらいら」などの心的状態と関係が強かった。心身の健康状態の把握のためには、健康観察などを通して、正確に子どもの状態を把握するとともに支援的に関わっていくことが重要であると考えられた。(著者抄録)

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本学校保健学会  

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Language：Japanese   Publisher：間脳・下垂体・副腎系研究会  

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/s0167-0115(99)00099-3

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To elucidate the contribution of the renin-angiontensin system (RAS) to glomerular injury in salt-sensitive hypertension, we investigated the chronic effects of the angiotensin I-converting enzyme inhibitor cilazapril and the angiotensin II type 1-receptor antagonist (AT_1a) TCV-116 in Dahl-Iwai rats. Dahl salt-sensitive (S) rats receiving 8% salt diet for 6 wk were simultaneously treated with cilazapril ( n = 6), TCV-116 ( n = 6), or saline ( n = 14). The 8% salt diet markedly increased systolic blood pressure (SBP), urinary protein, and N-acetyl-β-glucosaminidase (NAG) excretion compared with 0.3% salt-treated S ( n = 6) or salt-resistant ( n = 6) rats. Although neither cilazapril nor TCV-116 reduced the elevated SBP, TCV-116 significantly lowered urinary protein and NAG excretion. Histologically, 8% salt treatment in S rats induced progressive sclerotic and proliferative glomerular changes, which were ameliorated by both drugs. TCV-116 increased the glomerular diameter. Immunofluorescence demonstrated the increased level of type III collagen in the mesangium of 8% salt-treated S rats, which was completely reversed by TCV-116. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that 8% salt treatment significantly increased the levels of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor B-chain and that TCV-116 significantly reduced the levels of PCNA and transforming growth factor-β1 (TGF-β1). Thus, although the chronic RAS-inhibition in salt-sensitive hypertension exerted a histologically renoprotective effect by both ways without lowering blood pressure, the RAS inhibition due to AT_1ahad more beneficial advantages of reducing proteinuria and attenuating the levels of glomerular TGF-β1 and extracellular matrix.

DOI： 10.1152/ajpregu.1998.274.6.r1797

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DOI： 10.1016/s0167-0115(98)00009-3

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Language：English   Publisher：The Japanese Society of Internal Medicine  

A 49-year-old woman with Cushing's syndrome due to unilateral adrenal hyperplasia is presented. She had developed obesity and menopause for 2 years, but no hypertension or hypertrichosis was observed. Although plasma adrenocorticotropin and serum cortisol levels were within normal ranges, the circadian rhythm has completely disappeared. Free thyroxine and triiodothyronine levels were decreased. Adrenocorticotropin did not respond to corticotropin-releasing hormone, and urinary excretion of 17-hydroxycorticosteroids was not suppressed by dexamethasone. Abdominal computed tomography and ¹³¹I-Adosterol scintigraphy demonstrated a unilateral functioning mass in the left adrenal gland. The resected left adrenal mass was pathologically diagnosed as the rare condition of adrenocortical nodular hyperplasia.<br>(Internal Medicine 37: 385-390, 1998)

DOI： 10.2169/internalmedicine.37.385

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Other Link： https://jlc.jst.go.jp/DN/JALC/00084936899?from=CiNii

Language：English   Publisher：The Japan Endocrine Society  

A 49 year-old Japanese woman had subjected enlargement of a cervical tumor, and also suffered two bone fractures in 2 years. The cervical tumor had enlarged further in the month prior toadmission, becoming warm and tender. Endocrinological examination revealed that the serum intact PTH concentration was remarkably high at 400 pg/mL despite the low serum calcium concentration, and that the serum vitamin Ds concentration was decreased. Bone roentgenograms revealed severe osteolytic changes compatible with osteitis fibrosa cystica and a pathologic fracture of the humerus.Under a diagnosis of primary hyperparathyroidism, parathyroidectomy was performed, followed by fixation surgery for the pathologic fracture. Histologically, the cervical tumor was a parathyroid chiefcell adenoma with massive necrosis, and the bone pathology by iliac bone biopsy revealed the existence of osteomalacia. She was treated with calcium, vitamins D and K2 and calcitonin after the surgery. This case is a rare condition manifesting hypocalcemia with catastrophic osteoporosis under the coexistence of spontaneous infarction of parathyroid adenoma with osteomalacia, suggesting that the clinical features of hyperparathyroidism are modified by both the autoparathyroidiectomy and the existence of osteomalacia due to vitamin D deficiency.

DOI： 10.1507/endocrj.45.617

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DOI： 10.1016/s0167-0115(97)01041-0

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We report a 47-year-old Japanese man who presented with visual disturbance due to a pituitary tumor with suprasellar extension. The patient had mild secondary hypothyroidism preoperatively, and was started on administration of levothyroxine sodium immediately before transsphenoidal surgery. After the operation, levothyroxine sodium was continued for several months. Pathological examination of the surgical specimen, together with endocrinological investigation revealed that the suprasellar tumor was a FSH-producing pituitary adenoma. Since 3 months after the operation, he has developed muscle weakness and finger tremor. He was found to be thyrotoxicosis, and levothyroxine sodium was discontinued. Seven weeks after levothyroxine sodium was discontinued, thyrotoxicosis continued, with a positive thyrotropin binding inhibitory immunoglobulin (TBII) and a high diffuse ¹²³I-uptake by the thyroid. He was started on thiamazole 30mg/day. Although his thyroid dysfunction improved within 2 months, hyperthyroidism worsened repeatedly on attempts to discontinue thiamazole, and he required continuous treatment at 2.5mg/day. Patients with occult autoimmune thyroiditis rarely progress to thyrotoxicosis after operations on other endocrine organs such as the adrenal or parathyroid gland. In patients with pituitary adenoma, thyroid function and thyroid-associated autoantibodies should be investigated pre- and post-operatively.

DOI： 10.1507/endocrj.44.887

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The thyroid gland is physiologically stimulated in normal early pregnancy. This stimulated thyroid function is occasionally termed "gestational transient thyrotoxicosis". The cause of this thyrotoxicosis has been clarified to closely it associate with human chorionic gonadotropin (hCG). We encountered a pregnant patient with hyperemesis and thyrotoxicosis, who manifested symptoms of Wernicke encephalopathy. Although her serum hCG concentration transiently increased in accordance with the thyrotoxicosis, it was within normal limits for the gestational week. Both the thyrotoxicosis and a catabolic state due to the hyperemesis were thought to have induced a vitamin B1 deficiency, causing the Wernicke encephalopathy. This case suggests that pregnant patients with hyperemesis should undergo careful endocrinological and neurological evaluations.

DOI： 10.1507/endocrj.44.447

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We report a case of 77-year-old woman who presented with lumbago and hypercalcemia. Multiple myeloma (MM) was first diagnosed by serum protein electrophoresis and bone marrow aspiration, but intact parathyroid hormone (intactPTH) was also found to be high in the presence of persistent hypercalcemia with anorexia and nausea. After lowering serum calcium with bisphosphonate administration, parathyroidectomy was performed. Upon histologic examination, the tumor was determined to be parathyroidal chief-cell hyperplasia and the patient was treated with melphalan and prednisolone. The relationship between MM and primary hyperparathyroidism (I°HPT) remains unknown. Although the co-existence of MM and I°HPT was reported in 12 reports from various parts of the world, there was only 1 report in Japan. The present case is an example of successful treatment for a complicated disorder, and suggests that patients suffering from bone pain or hypercalcemia need to be examined both endocrinologically and hematologically.

DOI： 10.1507/endocrj.44.105

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We describe a case of diabetes insipidus (DI) due to a pituitary tumor in a 33-year-old pregnant woman who developed a sudden onset of polyuria (over 8l/day) and polydipsia at 30 weeks of gestation. Her plasma concentration of vasopressin (AVP) was low compared with high serum osmolality (298mOsm/kg), and her urine output was well controlled by treatment with desmopressin acetate (DDAVP). Cranial magnetic resonance imaging (MRI) demonstrated a 1.8×1.2-cm pituitary tumor, but she did not have any disturbance in the release of anterior pituitary hormones. The serum concentration of cystine aminopeptidase (CAP) was within the normal range for a woman at 34 weeks of gestation. After an uncomplicated delivery of a healthy girl, her polyuria gradually resolved. The size of the pituitary tumor gradually decreased in parallel to a reduction in her urine output, but a silent hemorrhage was detected in her pituitary gland 4 weeks after the delivery. Although pregnancy is sometimes associated with central DI, the occurrence of DI due to pituitary tumor under pregnancy is rare. The basal AVP recovered to within the normal range, but the low response of AVP secretion to high osmolality persisted. In this case, pregnancy may affect the manifestation of subclinical DI. This case may therefore enhance our understanding of the mechanisms of DI during pregnancy.

DOI： 10.1507/endocrj.43.577

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DOI： 10.2169/internalmedicine.52.9009

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Other Link： http://search.jamas.or.jp/link/ui/2012128362

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26歳女。動悸を契機にバセドウ病と診断され、チアマゾールで治療を開始したが、皮疹が出現したために内服を自己中断した。プロピルチオウラシル(PTU)に変更して、甲状腺機能の正常化を認めたが、肝機能障害が出現し、PTUを減量した。著明な肝機能障害の増悪を指摘され、PTUを中止し無機ヨード内服に変更となり、紹介入院となった。劇症肝炎に対しステロイドパルス、FFP輸注及びCHDFを行うも、肝萎縮の進行と肝性脳症が出現し、保存的加療での救命は困難と判断した。同胞(兄)をドナーとして、準緊急的生体部分肝移植を施行した。摘出肝の組織検査所見では、劇症肝炎に合致する所見であった。甲状腺は、移植後第6病日に甲状腺全摘出術を施行した。その後は肝機能も安定し、レボチロキシン補充を行い外来通院にて経過観察となった。移植肝は拒絶反応なく生着したことがCTにて確認した。

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPAN ENDOCRINE SOC  

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Language：English   Publisher：AMER PHYSIOLOGICAL SOC  

Goto J, Otsuka F, Yamashita M, Suzuki J, Otani H, Takahashi H, Miyoshi T, Mimura Y, Ogura T, Makino H. Enhancement of aldosterone-induced catecholamine production by bone morphogenetic protein-4 through activating Rho and SAPK/JNK pathway in adrenomedullar cells. Am J Physiol Endocrinol Metab 296: E904-E916, 2009. First published February 9, 2009; doi:10.1152/ajpendo.90840.2008.-Here we investigated the effects of mineralocorticoid in the regulation of catecholamine biosynthesis using rat pheochromocytoma PC12 cells. Expression of mineralocorticoid receptor (MR) was confirmed in undifferentiated PC12 cells. Aldosterone stimulated dopamine production by PC12 cells without any increase in cAMP activity. Aldosterone-induced dopamine accumulation was enhanced in accordance with the increase in the rate-limiting enzyme tyrosine hydroxylase (TH). Blocking MR with eplerenone suppressed aldosterone-induced increases of TH mRNA and dopamine production. A glucocorticoid receptor (GR) antagonist, RU-486, attenuated dexamethasone-but not aldosterone-induced TH expression. Cycloheximide reduced both aldosterone-and dexamethasone-induced TH mRNA. A SAPK/JNK inhibitor, SP600125, suppressed aldosterone-induced TH mRNA expression; however, the aldosterone-induced TH expression was not affected by inhibition of ERK1/2, p38-MAPK, Rho-kinase, PI 3-kinase, and PKC. It was of note that cotreatment with eplerenone and SP600125 restored aldosterone-induced TH mRNA expression to basal levels. To investigate the involvement of bone morphogenetic protein (BMP) actions in aldosterone-induced catecholamine production, we examined the effects of BMP-4 and BMP-7, which are expressed in the adrenal medulla, on catecholamine biosynthesis. BMP-4 preferentially enhanced aldosterone-induced TH mRNA and dopamine production, although BMP-4 alone did not affect TH expression. The BMP-4 enhancement of aldosterone-induced TH expression was not observed in cells treated with eplerenone. BMP-4 did not affect MR expression of PC12 cells; however, it did enhance aldosterone-induced SAPK/JNK phosphorylation. Inhibition of SAPK/JNK or Rho suppressed BMP-4 enhancement of aldosterone-induced TH expression. Collectively, our findings demonstrate that aldosterone stimulates catecholamine biosynthesis in adrenomedullar cells via MR through genomic action and partly through nongenomic action by Rho-SAPK/JNK signaling, the latter of which is facilitated by BMP-4. A functional link between MR actions and endogenous BMP may be involved in the catecholamine production.

DOI： 10.1152/ajpendo.90840.2008

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A 73-year-old Japanese woman was referred for examination of right flank pain and progressive hypertension. Abdominal CT incidentally detected a right adrenal mass 8 cm in size. The tumor exhibited isodensity by CT and contained high-intense lesion by T2-weighted MRI. Scintigraphy with I-131-metaiodobenzylguanidine and I-131-adosterol showed no abnormal uptake by whole body scan. Positron emission tomography scan with F-18-2-fluoro-D-deoxyglucose demonstrated an exclusive uptake in the right adrenal mass. Adrenocortical hormone levels and catecholamine secretion were within normal range; however, the level of serum neuron-specific enolase (NSE) was found to be markedly high. After controlling systemic blood pressure with an alpha 1-blocker, the right adrenal tumor was surgically removed, along with the right kidney and inferior vena cava which adhered to it. The tumor was pathologically proven to be leiomyosarcoma, which was immunohistochemically positive with a-smooth muscle actin and negative with CD57, S-100 and c-kit proteins. Notably, NSE protein was massively expressed in the resected tumor. After surgery blood pressure was controlled with regular medication and serum NSE levels have since normalized. The possibility of leiomyosarcoma should be kept in mind in adrenal incidentalomas with rapid growth and atypical radiological images. Our findings suggest that circulating NSE levels may be clinically useful for early detection of recurrence.

DOI： 10.1507/endocrj.K07E-020

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Involvement of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation and bone morphogenetic protein (BMP) signaling in regulating cell proliferation and hormonal production of pituitary tumors has been reported, although the underlying mechanism remains poorly understood. Here, we investigated regulatory roles of PPAR alpha. and PPAR gamma in gonadotropin transcription and cell mitosis modulated by pituitary activin/BMP systems using a mouse gonadotropinoma cell line L beta T2, which expresses activin/BMP receptors, transcription factor Smads, PPAR alpha, and PFARy. In L beta T2 cells, BMP signaling shown by Smad 1/5/8 phosphorylation and Id-1 transcription was readily activated by BMPs. A PPAR gamma agonist, pioglitazone significantly reduced BMP-induced DNA synthesis by L beta T2; whereas the PPARa agonist, fenofibric acid, did not. In accordance with the effects on cell mitosis, pioglitazone but not fenofibric acid significantly decreased BMP-induced Id-1-Luc activation. Neither fenofibric acid nor pioglitazone affected activin signaling detected by (CAGA)(9)-Luc activity. Both PPAR alpha and PPAR gamma ligands directly suppressed transcriptional activities of FSH beta, LH beta, and GnRHR. Activation of PPARg. and PPAK gamma increased mRNA levels of follistatin, but did not affect the expression of follistatin-related gene. Thus, PPAR agonists not only directly suppress gonadotropin transcription and BMP signaling, but also inhibit the biological actions of activins which facilitate gonadotropin transcription through upregulating follistatin expression. In addition, pioglitazone increased BMP ligands mRNA, but decreased activin-beta B mRNA in L beta T2 cells. Collectively, PPAR activation differentially regulates gonadotrope cell proliferation and gonadotropin transcription in a ligand-dependent manner.

DOI： 10.1677/JOE-07-0138

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Language：English   Publisher：SOC STUDY REPRODUCTION  

Bone morphogenetic proteins (BMPs) play critical roles in folliculogenesis by modulating the actions of follicle-stimulating hormone (FSH) in the ovary. However, the effects of FSH on the BMP system remain unknown. Here, we have investigated the effects of FSH on BMP signaling using the human granulosa-like tumor cell line KGN. KGN cells express BMP type 1 and type II receptors and the BMP signaling molecules SMADs. FSH administration upregulated BMP type IA (BMPR1A) and IB (BMPR1B) receptors, activin type II receptor (ACVR2), and BMP type II receptor (BMPR2). FSH also augmented SMAD1 and SMAD5 expression, and conversely, FSH suppressed the expression of the inhibitory SMADs, SMAD6 and SMAD7. Bioassays revealed that FSH enhances BMP-induced SMAD1/5/8 phosphorylation and cellular DNA synthesis induced by BMP6 and BMP7. Since overexpression of BMPR1A and BMPR1B, but not SMADs, significantly enhanced the BMP responses, these type I receptors were revealed to be limiting factors for BMP signaling in KGN cells. BMPs significantly suppressed progesterone synthesis induced by forskolin and dibutyryl-cAMP (BtcAMP) but had no effect on estradiol induced by the same factors. KGN cAMP levels induced by forskolin were not altered by BMPs, suggesting that BMPs regulate steroidogenesis at a level downstream of cAMP synthesis in KGN cells. In this regard, BMPs specifically reduced the STAR transcription, whereas the levels of CYP11A, HSD3B2, and CYP19 stimulated by forskolin as well as BtcAMP were not altered. Collectively, the two major factors, FSH-cAMP pathway and BMP system, are reciprocally and functionally linked. Given that BMPs downregulate FSH receptors in KGN cells, this interaction may contribute to finetuning of the mutual sensitivity toward BMP ligands and FSH.

DOI： 10.1095/biolreprod.105.047969

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Aldosterone production is modified by several growth factors that reside in the adrenal. We have recently reported the existence of a bone morphogenetic protein (BMP) system in human adrenocortical cells, in which BMP-6 augments aldosterone synthesis. Here, we investigated functional roles of BMP-\6, focusing on the differential regulation of aldosterone synthesis induced by angiotensin (Ang) II and potassium (K). In human adrenocortical H295R cells, BMP-6 augmented Ang II-induced CYP11B2 transcription and mRNA and aldosterone roduction but had no effect on K-induced aldosterone production. Inhibition of endogenous BMP-6 action by neutralizing antibodies impaired aldosterone production induced by Ang II but not that induced by K. Blockage of ligand-receptor binding using extracellular domain (ECD) of BMP type I receptors revealed that ECDs to activin receptor-like kinase (ALK)-2 and ALK-3 significantly reduced the aldosterone production induced by Ang II. None of the type I-receptor ECDs tested had any effect on K-induced aldosterone levels. Overexpression of a dominant negative-activin type II receptor construct selectively decreased Ang II-induced aldosterone production without having any effect on K-induced aldosterone production. BMP type II receptor-dominant negative had no effect on aldosterone induced by either Ang II or K. These results infer that BMP-6 acts through ALK-2, ALK-3, and activin type II receptor receptors in adrenocortical cells. BMP-6 pretreatment extends the induction of ERK1/2 phosphorylation by Ang II and treatment with ECDs to ALK-2 and ALK-3 impaired Ang II-induced ERK phosphorylation. The specific inhibitor of ERK activation, U0126, suppressed the activation of CYP11B2 transcription induced by BMP-6 without affecting Smad phosphorylation and Tlx2-Luc activity. Collectively, the endogenous BMP-6 system plays critical roles in aldosterone production between Ang II and K through ERK signaling pathway.

DOI： 10.1210/en.2005-1250

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Language：English   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

We uncovered a new regulation of thyrocyte function by bone morphogenetic protein (BMP) under the influence of thyrotropin (TSH) using primary culture of porcine thyrocytes. The BMP type I receptors, ALK-2 (ActRIA), -3 (BMPRIA), and -6 (BMPRIB), were expressed in porcine thyrocytes, while ALK-6 was not detected in human thyroid. Treatment with BMP-2,-4,-6,-7, and TGF-beta1 exhibited a dose-dependent suppression of DNA synthesis by porcine thyrocytes. BMP-2, -4, -6, -7, and TGF-beta1 suppressed TSH receptor mRNA expression on thyrocytes, which was consistent with their suppressive effect on TSH-induced cAMP synthesis and TSH-induced insulin-like growth factor-1 expression. Activin exhibited minimal suppression of thyrocyte DNA synthesis and did not exhibit suppressive effects on TSH receptor mRNA expression. Phosphorylated Smad1/5/8 was detected in the lysates of porcine thyrocytes treated with BMP-2, -4,-6, and -7. However, in the presence of TSH, BMP-6 and -7 failed to activate Smad1/5/8 phosphorylation and 3TP-reporter activity, whereas BMP-2 and -4 maintained clear activation of the BMP signaling regardless of the presence of TSH. This diverged regulation of thyroid BMP system by TSH is most likely due to the reduction of ALK-6 expression caused by TSH. Thus, the thyroid BMP system is functionally linked to TSH actions through modulating TSH receptor expression and TSH, in turn, selectively inhibits BMP signaling. Given that BMP system is present in human thyroid and the expression pattern of ALK-2 and BMPRII is different between follicular adenomas and normal thyroid tissues, the endogenous BMP system may be involved in regulating thyrocyte growth and TSH sensitivity of human thyroid adenomas. (C) 2004 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2004.12.122

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Language：Japanese   Publisher：間脳・下垂体・副腎系研究会  

56歳男.健診にて血糖異常を指摘されスクリーニングCTにて右副腎腫瘍を認め,精査目的で入院した.アドステロールシンチを含む検査結果より,非機能性副腎腺腫が疑われたため外来経過観察とした.6ヵ月後右腹部から右腰背部に鈍痛が出現し,腹部画像検査にて副腎腫瘍の増大を認め,腫瘍内出血を疑い入院した.副腎腫瘍はホルモン産生を欠き,両側性であること,非常に急速に増大していることから,副腎癌,転移,悪性リンパ腫などが考えられたが,ガリウムシンチ・骨シンチでリンパ節転移は否定された.開腹手術により両側性副腎摘出術を施行し,副腎組織に腺癌浸潤像を認めた.術後,FDG-PET検査にて左上肺野に有意な核種取り込みを認め,肺腺癌の両側副腎転移として化学療法を行ったが,肺のブラ所見に変化は認められなかった

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Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.amjhyper.2004.03.672

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Language：English   Publisher：W B SAUNDERS CO  

The aim of the present study was to determine the change of serum uric acid (UA) levels in male adolescents and to characterize the relationship between UA levels and obesity or its related factors. This study was conducted in 17,155 students at enrollment in Okayama University from 1991 through 2002, in which the mean serum UA level as a whole was 5.64 +/- 0.009 mg/dL (mean +/- SEM) and the incidence of hyperuricemia (greater than or equal to7.6 mg/dL) was 4.13%. Serum UA levels were correlated with obesity-related indicators, including body mass index (BMI; r = 0.282, P &lt; .0001) and skin-fold thickness (r = 0.286, P &lt; .0001). The incidence of hyperuricemia was increased in parallel with BMI. In the last 4 years (1999 through 2002) of the study period, serum UA levels (5.76 mg/dL) and the incidence of hyperuricemia (4.5%) were significantly increased compared with those in the earlier period (1991 through 1994: 5.50 mg/dL and 3.5%, respectively). However, BMI has been rather gradually decreased throughout 12-year observation in all the subjects. Hyperuricemia was related to the presence of other risk factors, including hypercholesterolemia, liver function abnormality, and hypertension. The frequencies of such abnormalities were higher than euuricemic subjects and this trend was notable in the most recent students enrolled from 1999 through 2002. Hyperuricemia was even found in the group of non-obese male adolescents. Taking into consideration that hyperuricemia is associated with a high prevalence of lifestyle-related diseases in adults, it is of great importance to prevent hyperuricemia at the early stage in Japanese adolescents. (C) 2004 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.metabol.2003.11.017

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Language：Japanese   Publisher：Hirosaki University  

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Other Link： http://hdl.handle.net/10129/613

Language：Japanese   Publisher：日本保健医療行動科学会  

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Other Link： http://search.jamas.or.jp/link/ui/2005046426

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Language：Japanese   Publisher：間脳・下垂体・副腎系研究会  

19歳女.妊娠後33週より高血圧・蛋白尿が出現し,35週には浮腫と体重増加を伴う妊娠中毒症を呈した.食事療法と安静によって妊娠36週に経腟分娩で男児を出産した.しかし,出産後も体重増加と高血圧が持続し,産後4ヵ月には尿路結石にも罹患した.血中ACTH高値とコルチゾール高値を認めたためクッシング症候群を疑い,入院となった.精査によりクッシング病と診断し,外来で経過観察を続けた.クッシング徴候が臨床的に増悪したため,経蝶形骨洞的下垂体腫瘍摘出術を施行した.摘出した下垂体腫瘍は免疫組織学的にACTH産生性腺腫であった.現在は長時間作用ドパミンアゴニストであるカベルゴリンによる後療法を行い経過観察中であるが再発は認めていない

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：JAPAN ENDOCRINE SOCIETY  

DOI： 10.1507/endocrj.50.835

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Language：English   Publisher：EDITRICE KURTIS S R L  

We report a 22-yr-old male patient with idiopathic hypothalamic hypogonadism who showed secondary resistance to gonadotropin (Gn) therapy over 3 yr after successful treatment with hCG combined with human menopausal Gn. The patient simultaneously developed subclinical hypothyroidism. Endocrine examination revealed low levels of testosterone (0.3 ng/ml), free T-4 (0.91 ng/dl), and increased levels of TSH (31.1 muU/ml) in the serum. Serum autoantibodies to thyroid gland were all negative. Interestingly, thyroid function was improved after discontinuation of Gn therapy. In vitro assays by immunoprecipitation using (125)l-hCG or (125)l-TSH elucidated the presence of anti-hCG antibody in the serum 13 months after commencement of Gn therapy but anti-TSH antibody was not detected in the serum. Furthermore, the anti-hCG antibody specifically bound to hCG but not to other glycoproteins including TSH and FSH based on a competitive displacement assay. Bioassays using porcine thyroid cells revealed that the serum gamma-globulin fraction enables the suppression of cyclic AMP (cAMP) synthesis stimulated by TSH. Our findings suggest that anti-hCG and/or anti-idiotypic hCG antibodies induced by hCG therapy impaired TSH-dependent cAMP production through interfering with binding of TSH to its receptor, and this resulted in subclinical hypothyroidism in this patient. (C) 2003, Editrice Kurtis.

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Language：English   Publisher：JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE  

To elucidate whether bradykinin is involved in the renoprotective effect produced by angiotensin II type 1 receptor antagonist (AT1A) in chronic salt-sensitive hypertension, Dahl salt-sensitive rats receiving a high-salt (8%) diet were treated either with an AT1A (candesartan, 1 mg/kg/day), a bradykinin B2 receptor antagonist (BKB2A; FR172357, 30 mg/kg/day) or a combination of AT1A and BKB2A for 7 weeks. None of the treatments changed the markedly increased systolic blood pressure induced by a high-salt diet. However, chronic treatment with AT1A significantly improved the histological hallmarks of renal damage-i.e., glomerular sclerosis and cell proliferation-despite the presence of severe hypertension. This beneficial action of AT1A was abolished by the concomitant administration of BKB2A. In agreement with these histologically based findings, increases in levels of creatinine clearance induced by AT1A were also reversed back to the basal levels when BKB2A was administered in conjunction with AT1A. Furthermore, urinary excretions of nitrate plus nitrite and prostaglandin E-2 increased moderately in response to the administration of AT1A alone, but not in combination with BKB2A. Thus, the blockade of bradykinin signaling abrogates the renoprotective actions of the angiotensin II type 1 (AT1) receptor antagonism. Collectively, these data show that when AT1 action is chronically blocked, endogenous bradykinin plays a pivotal role in preventing the progression of glomerular injury in salt-sensitive hypertension.

DOI： 10.1291/hypres.26.265

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Language：English   Publisher：KARGER  

Aim:The roles of adrenomedullin (AM) in body fluid balance under general anesthesia were investigated. Methods: Time course changes in plasma osmolality, AM, arginine vasopressin (AVP), and urinary aquaporin 2 (AQP2) in 17 patients undergoing abdominal surgery under general anesthesia were examined. Results: Increases in plasma AM levels were observed in parallel with increases in the levels of urinary AQP2/creatinine (Cr) before induction and 90 and 180 min after initiation of anesthesia. Significant correlations between plasma AM and urinary AQP2/Cr (r = 0.62, p &lt; 0.0001) as well as urinary AVP/Cr and AQP2/Cr (r = 0.60, p &lt; 0.0001) were uncovered. Multivariate stepwise analysis identified plasma AM as the critical independent factor affecting urinary AQP2/Cr level. Conclusion: A novel correlation of AM and AQP2 which overlays an AVP-AQP2 system may play a key role in fluid homeostasis during general anesthesia. Copyright (C) 2003 S. Karger AG, Basel.

DOI： 10.1159/000067933

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Language：Japanese   Publisher：日本教育大学協会第二常置委員会  

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Other Link： http://search.jamas.or.jp/link/ui/2004089555

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Other Link： http://search.jamas.or.jp/link/ui/2004089555

Language：English   Publisher：NATURE PUBLISHING GROUP  

OBJECTIVE: To investigate whether the changes in IGF-1 concentrations after weight reduction in Japanese overweight men are associated with changes in visceral and subcutaneous fat.
DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education.
SUBJECTS: One-hundred and twelve Japanese overweight men aged 30-59y (body mass index (BMI) 28.4+/-2.5 kg/m(2)) and 33 normal-weight men aged 30-39y (BMI 22.1+/-1.5 kg/m(2)) at baseline. From the participants, 56 randomly selected overweight men (BMI 28.8+/-2.8) were further enrolled into a 1 y exercise program.
MEASUREMENTS: Fat distribution was evaluated by visceral fat M and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, metabolic parameters and hormones including insulin, leptin and IGF-1 at baseline and after 1 y.
RESULTS: In 112 overweight subjects at baseline, insulin (10.5+/-5.0 muUl/ml) and leptin (6.4+/-3.7 ng/ml) significantly correlated with both V (r=0.260, P=0.0073; r=0.410, P&lt;0.0001) and S areas (r=0.377, P&lt;0.0001; r=0.613, P&lt;0.0001), respectively. IGF-1 (156.8+/-48.7 muU/ml) significantly and negatively correlated with V area (r= -0.242, P=0.0125)and age (r= - 0.192, P=0.0480). In normal-weight men aged 30-39y (n=33) and age-matched subjects (n=30) selected from the 112 overweight men, the serum IGF-1 further tightly correlated with V area (r= - 0.467, P&lt;0.0001). Visceral fat area and age were independently related to serum IGF-1 levels by multiple regression analysis. By intervention with exercise education, 56 overweight subjects showed an increase in daily steps (6224+/-2781 to 7898+/-4141 steps/day) and reduction of BMI (28.8+/-2.8 to 27.7+/-2.9). DeltaIGF-1 significantly correlated with DeltaV area (r= - 0.432, P = 0.0009) but not with DeltaS area or DeltaBMI.
CONCLUSION: The present study indicated a negative correlation between IGF-1 levels and visceral fat at baseline as well as an association between the reduction in visceral fat and increase in IGF-1 levels after an exercise intervention.

DOI： 10.1038/sj/ijo/0801899

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：English   Publisher：JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE  

We report a Japanese family with glucocorticoid-remediable aldosteronism (GRA) in whom gene abnormality was identified by the long-polymerase chain reaction (PCR) method. The proband was a 21-year-old female incidentally found to have high blood pressure (173/107 mmHg). Laboratory tests showed hypokalemia (3.7 mmol/l), and high plasma aldosterone concentration (PAC, 234 pg/ml) with suppressed plasma renin activity (PRA, &lt; 0.1 ng/ml/h). The circadian rhythm pattern and the results of a rapid adrenocorticotrophic hormone (ACTH) test indicated ACTH-dependent changes in PAC. Imaging studies showed no adrenal mass on either side. A dexamethasone (Dexa) suppression test (1.0 mg/day orally for 7 days) showed a marked decrease of PAC 2 days after administration, and this decreased level was maintained throughout Dexa administration. High blood pressure and hypokalemia also improved during Dexa treatment. The proband's younger sister was 19 years old and had hypertension, PAC of 231 pg/ml, and PRA &lt; 0.1 ng/ml/h. The mother was 53 years old and had hypertension, PAC of 98.5 pg/ml, and PRA &lt; 0.1 ng/ml/h. The proband's elder sister was a 22-year-old normotensive with PAC of 110 pg/ml and PRA of 0.1 ng/ml. Long-PCR was performed for detection of the chimeric gene associated with GRA, using DNA samples from all four cases and two normal control subjects. Although the aldosterone synthase gene was expressed among all DNA samples, the chimeric gene was detected only in the proband, her younger sister and her mother. Our clinical data and genetic investigation confirmed the presence of GRA in this Japanese family.

DOI： 10.1291/hypres.24.589

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Language：English   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

We investigated the effects of long-term treatment with calcium-antagonist, amlodipine, on angiotensin II receptors in the adrenal cortex of spontaneously hypertensive rats (SHR). Seven-week-old male SHR were treated with oral amlodipine (10 mg/kg/day) or vehicle (saline) for four weeks. Age-matched normotensive Wistar-Kyoto (WKY) rats were treated with the vehicle similar to control SHR. Systolic blood pressure (SBP) showed time-dependent increase in SHR but not in WKY rats, while amlodipine treatment significantly reduced the high SEP in SHR, Plasma renin activity was serially increased in SHR, which was further enhanced by amlodipine treatment, But the plasma aldosterone level which was increased in SHR was not changed by amlodipine. Competitive reverse transcriptase-polymerase chain reaction showed that the level of adrenocortical angiotensin II type 1 receptor (AT1R) mRNA progressively decreased in vehicle-treated SHR compared to WKY rats and that 4-week course of amlodipine treatment significantly increased AT1R mRNA in SHR to levels comparable to those in WKY rats. Amlodipine treatment reduced the level of adrenocortical angiotensin II type 2 receptor (AT2R) mRNA in SHR from 8 weeks of age. Thus, chronic amlodipine treatment differently modulates both adrenocortical AT1R and AT2R in SHR in a possibly direct manner, (C) 2001 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0024-3205(01)01071-2

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Language：English   Publishing type：Book review, literature introduction, etc.   Publisher：JAPAN ENDOCRINE SOCIETY  

We report a rare case of Graves' disease associated with struma ovarii. A 26-year-old Japanese woman had preexisting Graves' disease and was positive for TSH receptor antibody. She had been on antithyroid medication at presentation. She noted a mass in the lower left abdomen, which was diagnosed as a left struma ovarii by radiological work-up including computed tomography, magnetic resonance imaging and scintigraphy. The surgically excised teratomatous tumor, containing cystic spaces with thyroid tissue, was histologically proved to be struma ovarii. Since thyroid function tests and TSH receptor antibody did not change after surgery, her hyperthyroidism was considered to be due to Graves' disease. Our case was diagnosed as struma ovarii before surgery using various imaging studies.

DOI： 10.1507/endocrj.48.255

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Language：English   Publisher：ELSEVIER SCIENCE INC  

To elucidate the role of nitric oxide (NO) and renin angiotensin system (RAS) in the development of salt-sensitive hypertension, we investigated the presser responses and renal histologic changes after long-term inhibition of endogenous NO synthesis in Dahl-Iwai salt-sensitive (DS) and salt-resistant (DR) rats under salt-restricted conditions that exaggerate RAS activation. Male DS and DR rats (6 weeks old) were fed with a low-salt (0.3%) diet for 5 weeks, N-G-nitro-L-arginine (L-NA: dissolved in 60 mg/L deionized water), an arginine analogue acting as a NO-inhibitor, was also administered for 5 weeks. L-NA administration induced a gradual increase in systolic blood pressure (SBP) in both strains, and the presser response in DS rats was apparently more enhanced relative to that in DR rats. Urinary nitrate plus nitrite (u-NOx) excretion was decreased by L-NA, with a significant negative correlation between SEP and u-NOx excretion in DS rats but not in DR rats. Plasma renin activity and urinary aldosterone level were significantly increased in L-NA-treated DS rats on week 5. Marked histologic changes with glomerular sclerosis and increased protein-uria and urinary N-acetyl-beta -glucosaminidase excretion were found in L-NA-treated DS rats but not DR rats. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that angiotensin II type 1 receptor (AT(1)R) mRNA level was significantly lower in DS rats than in DR rats at week 2, and that L-NA administration significantly reduced glomerular AT(1)R level of DS rats at week 5, possibly because of downregulation. Our results showed that, even under sodium restriction, the presser response and renal injury induced by chronic NO inhibition were markedly more enhanced in DS rats than in DR rats, which indicates that depletion of NO participates in both the development of hypertension and glomerular injury in DS rats through a potential activation of RAS irrespective of sodium loading. These data suggest that endogenous NO is an essential determinant of salt-sensitive hypertension in DS rats. (C) 2001 American Journal of Hypertension, Ltd.

DOI： 10.1016/S0895-7061(00)01255-3

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Language：English   Publisher：JAPAN ENDOCRINE SOCIETY  

A 27-year-old woman who presented with a left thyroid nodule was found to have hyperthyroidism caused by a syndrome of inappropriate secretion of TSH. The levels of free T-3, free T-4 and TSH were 9.50 pg/mL, 4.05 ng/dL and 2.16 muU/mL, respectively. Magnetic resonance imaging of the head revealed a pituitary macroadenoma. The TSH response to TRH stimulation was normal and responses of other anterior pituitary hormones to stimulation tests were also normally preserved. Administration of octreotide with iodine successfully reversed hyperthyroidism prior to total resection of pituitary adenoma, which was followed by hemithyroidectomy of the left thyroid five months later. Histologically, the resected pituitary adenoma was a TSH-producing adenoma (TSH-oma) and the thyroid nodule was a papillary adenocarcinoma. Serum TSH diminished to undetectable levels immediately following pituitary adenomectomy but gradually normalized over nine months. Coexistence of a TSH-oma with thyroid cancer is very rare and only two similar cases have previously been documented. This combination raises the possibility that TSH may be involved in tumorigenesis in the thyroid gland.

DOI： 10.1507/endocrj.47.731

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Language：English   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

We have investigated the in vivo effect of chronic blockade of Ca2+-channels and angiotensin II type I (AT(1))-receptors on aldosterone (Aldo)-synthesis in the adrenal glands of spontaneously hypertensive rats (SHR). Male SHR were administered Ca2+-antagonist, amlodipine (10 mg/kg per day) or AT(1)-receptor-antagonist, TCV-116 (1 mg/kg per day) from 7 until 11 weeks of age. Systolic blood pressure (SBP) and heart rate (HR) were significantly higher in SHR than Wistar-Kyoto (WKY) rats. Both treatments resulted in equivalent and significant reduction in SEP in SHR. Aldo-secretion in SHR, which was significantly higher than in WKY rats, was profoundly suppressed by TCV-116 compared with amlodipine. Both treatments resulted in thickening of the tuna glomerulosa, which immunohistochemically contains Aldo, at the end of therapy. Competitive reverse transcription-polymerase chain reaction (RT-PCR) showed that CYP11A (P450scc) mRNA regulating the first step of Aldo-synthesis was significantly reduced from week 9 of age by amlodipine, and that CYP11A (P450aldo) mRNA regulating the last step of Aldo-synthesis was potently suppressed from 9 weeks of age by TCV-116. Our results indicate that chronic treatment with different antihypertensive agents directly modulates adrenocortical aldosterone synthesis in SHR in vivo via different mechanisms. (C) 2000 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0960-0760(00)00096-0

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Language：English   Publisher：EDITRICE KURTIS S R L  

Serial measurements of body mass index (BMI), serum concentrations of testosterone (T), estradiol (E) and leptin (L) were performed before and after gonadotropin (Gn) therapy in an 18-year-old male subject (BMI 25.4 kg/m(2)) with idiopathic hypothalamic hypogonadism (IHH). We also measured the BMI and serum concentrations of L in 99 age-matched healthy subjects. Serum L correlated significantly with BMI in control subjects (r=0.84, p&lt;0.0001). Baseline serum concentrations of L in our case were markedly high and both T and E were very low, but On therapy resulted in a gradual decrease in L and improvement in T and E, finally reaching the control levels of BMI-matched subjects. Our results demonstrate that T is a powerful negative modulator of serum L independent of BMI in conditions associated with low T levels, such as IHH. (C) 2000, Editrice Kurtis.

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Language：English   Publisher：JAPAN ENDOCRINE SOCIETY  

A 51-year-old woman who had been treated with levothyroxine sodium because of hypothyroidism after total thyroidectomy for thyroidal cancer was admitted to our hospital for persistent hypothyroidism despite large dose administration of levothyroxine (600 mu g/day). The patient complained of severe general fatigue and body weight gain. Free thyroxine, free triiodothyronine and thyrotropin levels were 0.97 ng/dl, 1.55 pg/ml and 24.51 mu U/ml, respectively, under oral administration of levothyroxine. Levothyroxine loading test performed by liquid form, pulverized tablets via nasogastric tube and intravenous administration revealed no evidence of malabsorption or metabolic disorder of levothyroxine, although oral intake of tablets was ineffective due to her factitiousness. We report here a possible case of "pseudomalabsorption of levothyroxine" to emphasize the clinical recognition of this disorder in patients with resistant hypothyroidism.

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Language：English   Publisher：Springer Japan  

Background: We aimed to elucidate the involvement of the renin-angiotensin system (RAS) and sympathetic nervous system in hypertension induced by the long-term inhibition of nitric oxide (NO) production. Methods: We compared the effects of 9-week treatment with an angiotensin-converting enzyme inhibitor (ACEI), cilazapril (10 mg/kg per day), to that with an α1-adrenoceptor antagonist, doxazosin (10 mg/kg per day), on systemic blood pressure and renal histological changes in Sprague-Dawley rats continuously treated with oral N(G)nitro-L-arginine (L-NA). Results: L-NA induced renal damage associated with a significant fall in urinary nitrate and nitrite (NOx) excretion and a significant rise in systolic blood pressure. Although cilazapril and doxazosin restored urinary NOx to a similar level, only cilazapril treatment significantly suppressed the hypertensive effect of L-NA. Urinary protein excretion in L-NA-treated rats was also significantly reduced by cilazapril treatment. Histologically, treatment with cilazapril, but not doxazosin, significantly inhibited the glomerular injury of mesangial expansion and glomerular sclerosis induced by L-NA treatment. Furthermore, cilazapril significantly reduced urinary aldosterone level. Conclusion: Our findings indicate that the hypertension and hypertensive glomerular injury induced by long-term L-NA treatment were abrogated by an ACEI but not by an α1- adrenoceptor antagonist, and that the fall in high blood pressure induced by treatment with the ACEI was independent of urinary NOx excretion in this model.

DOI： 10.1007/PL00012163

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Language：English   Publisher：P J D PUBLICATIONS LTD  

To identify the serum factors that affect circulating leptin levels, we measured the serum concentrations of leptin, testosterone (T), estradiol (E), serum alanine aminotransferase, total cholesterol and uric acid (UA) in healthy male adolescents (age, 18.3 +/- 0.1 years, n=96). We also measured body mass index (BMI), percent body fat and thickness of skin fold to assess the effect of body constitution on serum leptin level. Since serum concentration of leptin significantly correlated with BMI (r=0.820, p&lt;0.001), we analyzed the relation-ship between leptin/BMI ratio (L/BMI) and serum parameters. Analysis of data of subjects with normal serum T level showed a significant inverse correlation between L/BMI and serum T levels (n=96, r=-0.294, p&lt;0.005), but no such correlation was present among non-obese subjects (n=70) with BMI of +/- 20% of normal (22 kg/m(2)). There was no correlation between L/BMI and serum E level. Serum UA level significantly correlated with L/BMI in both the test group (n=96, r=0.520, p&lt;0.001) and non-obese subjects (r=0.369, p&lt;0.005). Stepwise multiple regression analysis showed that UA independently and significantly influenced serum leptin levels in both the test and control groups. Our results demonstrate that T weakly influences serum leptin concentration, and that UA concentrations strongly influences serum leptin in healthy male adolescents independent of their obesity level.

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Language：Japanese   Publisher：日本養護教諭教育学会誌編集委員会  

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Language：English   Publisher：KARGER  

We investigated the effect of barnidipine hydrochloride, a Ca2+ chan nel blocker, on the glomerular level of mRNA expression of platelet-derived growth factor (PDGF) B-chain and transforming growth factor (TGF)-beta(1) in spontaneously hypertensive rats (SHR) with reverse transcription and polymerase chain reaction. Thirteen-week-old SHR were provided with food containing barnidipine (0.6 mg/g of food, average dose during treatment: 53 mg/kg of body mass/day) for 3 weeks. A stable reduction in systolic blood pressure relative to that of age-matched control SHR was recorded after week 1 of therapy. Although no renal histological changes were observed after 3 weeks of treatment with barnidipine, the level of expression of PDGF B-chain mRNA in glomeruli was significantly reduced relative to that in control SHR, The glomerular level of TGF-beta(1) mRNA expression was not affected by the treatment, Treatment with barnidipine significantly reduced the excretion of urinary protein, Thus, the stable reduction in systemic blood pressure by barnidipine is associated with a reduction in PDGF B-chain mRNA expression in the glomerulus and reduction in urinary protein excretion in SHR. Copyright (C) 1999 S. Karger AG, Basel.

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Language：English   Publisher：JAPAN ENDOCRINE SOCIETY  

We report a case of giant cystic insulinoma constituting part of multiple endocrine neoplasia (MEN) type I. A 29-year-old Japanese man presented with a history of recurrent hypoglycemic attacks. Endocrine examination showed hyperinsulinemia discordant with hypoglycemia, and a giant cystic insulinoma (11 x 10 cm) located in the pancreatic tail was detected radiologically. Hyperprolactinemia due to pituitary adenoma and hyperparathyroidism due to parathyroid hyperplasia were also present. The insulinoma, prolactinoma and hyperplastic parathyroid gland were surgically removed. Fluorescent microsatellite analysis detected loss of heterozygosity (LOH) in chromosome 11q13 in DNA samples from all resected tissues but not from white blood cells. This is a rare case of MEN type I because of the giant cystic insulinoma and the evidence of common LOH detected in all MEN type I tissues.

DOI： 10.1507/endocrj.46.429

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Language：English   Publisher：CHURCHILL LIVINGSTONE  

The effects of long-term adrenocorticotropin (ACTH) therapy on the expression of IGF-I and TGF-beta(1) on rat adrenal cortex was investigated. ACTH (0.1 mg/kg/day) or saline as control was injected intraperitoneally in 5-week-old Wistar rats every day for 4 weeks. ACTH significantly increased adrenal weight (P&lt;0.05) and serum corticosterone (P&lt;0.05). Competitive RT-PCR analysis on the adrenocortical mRNA showed increased IGF-I (P&lt;0.01) at 4 weeks of ACTH and increased TGF-beta(1) (P&lt;0.01) at 1 week of ACTH compared the control group. ACTH also significantly increased proliferating cell nuclear antigen mRNA level (P&lt;0.01), at 4 weeks of treatment, which correlated with IGF-I level (P&lt;0.01), but correlated negatively with ACTH-stimulated TGF-beta(1) level (P&lt;0.05). There was a weak correlation between IGF-I and serum corticosterone (P&lt;0.05), and between TGF-beta(1) mRNA levels and serum corticosterone concentration (P&lt;0.05). Histologically, ACTH induced hypertrophy in the zona fasciculata cells and increased the clear cells containing lipid deposits. Immunohistochemistry showed that IGF-I peptide was mainly expressed in the periphery of the zona fasciculata at 4 weeks of ACTH therapy, while the same therapy caused a slight increase in TGF-beta(1) expression in the same area. Our results show that an increase in adrenocortical growth resulting from ACTH treatment is associated with an increase in IGF-I mRNA expression but only a transient increase in TGF-beta(1) mRNA expression. (C) 1999 Churchill Livingstone.

DOI： 10.1054/ghir.1998.0086

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Language：Japanese  

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Other Link： http://ousar.lib.okayama-u.ac.jp/13693

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Language：English   Publisher：P J D PUBLICATIONS LTD  

To elucidate the precise localization of angiotensin II (Ang II) type 1 (AT(1)) receptor in the kidney, we utilized in vitro macro- and micro-autoradiography (ARG) of [H-3]-Ang II bindings to the Wistar rat kidney in the presence of L158,809, a specific non-peptide AT(1) receptor antagonist. Besides, we estimated the density of renal AT, receptors using the quantification of macro-ARG. The density of [H-3]-Ang II binding to renal tissue was concentration-dependent in both renal cortex and medulla Although the addition with 500 nM arginine vasopressin and 500 nM atrial natriuretic peptide had no effect on [H-3]-Ang II, the total binding of [H-3] Ang II completely displaced by the addition with 500 nM unlabeled Ang II or L-158,809. Macro-ARG revealed that the amount of both Ang II and AT, receptors in the renal medulla gready exceeded those in the renal cortex In the medulla, the density of these receptors was not localized on the outer medulla but was confirmed mainly to the inner medulla, especially to the inner zone and longitudinal bands. Since the density and localization of AT(1) receptors was consistent with that of total Ang II receptors, it appears that AT(1) receptors comprise most of the Ang II receptors in the kidney. Micro-ARG revealed that Ang II receptors were mainly located in the glomerulus and proximal tubules of the renal cortex, as well as on the circumferences of vessels and the vasa recta of the renal medulla. The present study established a method for ARO of AT(1) receptors in the kidney as well as a method for quantifying the macro-ARG.

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Language：English   Publisher：P J D PUBLICATIONS LTD  

To assess the involvement of angiotensin II (Ang II) in the regulation of blood pressure, we investigated the alterations of renal Ang II type 1 (AT(1)) receptors in two different models of hypertension; i.e., in spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats by using the method for quantification of in vitro macroautoradiography (ARG). In the SHR model, although the number of cortical AT(1) receptors equaled that of Wistar Kyoto (WKY) rats at 4 and 12 weeks of age, the number of medullary AT(1) receptors in the 4-week-old SHR animals was significantly lower than that in age-matched WKY rats, and increased by 12 weeks of age. The renal AT(1) receptor number in DOCA-salt hypertensive rats was significantly higher than that in control rats. The amount of these receptors also increased with age in both DOCA-salt hypertensive rats and control rats. These findings indicate that the development of medullary AT(1) receptors in early stages of hypertension in the SHR model differs from that in WKY rats or DOCA-salt hypertensive rats. This suggests that renal AT(1) receptors may contribute to the hypertension seen in the SHR group. The renal AT(1) receptors appear to be up-regulated in early stages of DOCA-salt-induced hypertension as well.

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Language：English  

To elucidate the precise localization of vasopressin(VP) Vj and V2 receptors in the kidney, we utilized in vitro macroautoradiography (macro-ARG) and microautoradiography (micro-ARG) of these receptors in Wistar rat kidneys.This was done by using OPC-21268 and OPC-31260, two newly developed selective Vi (OPC-21268) and V2 (OPC-31260)receptor antagonists. For macro-ARG, 10-μm kidney sections were incubated with Tris-HCl buffer containing [3H]-VP with or without unlabeled ligand (VP, OPC-21268, orOPC-31260) at 20°C for 40 min. These sections were then loaded intoX-ray cassettes with Hyperfilm-[3H] and exposed inthe dark for 2 months. The autoradiograms were quantitativelyanalyzed by using the research analysis system RAS 1,000
the V1 and V2 receptors were quantitated by inftracting the nonspecific binding (incubatedwith OPC-21268 and OPC-31260, respectively) from the total binding. To assess a more precise localization of the V1and V2 receptors, we also investigated the micro-ARG of the renal V1 and V2 receptorsby dipping the kidney section slides used for macro-ARG into a photographic emulsion and observing the receptors under light microscopy. [3H]-VP binding to the rat kidney was completely displaced by unlabeled excess VP, but not by unlabeled angiotensin II, indicating that [3H]-VP binding was specific for VP receptors. Computerized quantification showed that V2 receptors, visualized by OPC-31260, were the predominant type of VP receptor in the kidney. Conversely, V1receptors, visualized by OPC-21268, werefewer in number. V) receptors were partly localized to the glomerulus, cortical vessels, interstitial cells, and the medullary vessels. The V2receptors localized to the collecting ducts and medullary tubules. Our findings indicated that renal V1 and V2 receptors can be detected by in vitro macro- and micro-ARG by using OPC-21268 and OPC-31260. © 1997 S.Karger AG, Basel.

DOI： 10.1159/000190200

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Language：English  

To elucidate the precise localization of vasopressin(VP) Vj and V2 receptors in the kidney, we utilized in vitro macroautoradiography (macro-ARG) and microautoradiography (micro-ARG) of these receptors in Wistar rat kidneys.This was done by using OPC-21268 and OPC-31260, two newly developed selective Vi (OPC-21268) and V2 (OPC-31260)receptor antagonists. For macro-ARG, 10-μm kidney sections were incubated with Tris-HCl buffer containing [3H]-VP with or without unlabeled ligand (VP, OPC-21268, orOPC-31260) at 20°C for 40 min. These sections were then loaded intoX-ray cassettes with Hyperfilm-[3H] and exposed inthe dark for 2 months. The autoradiograms were quantitativelyanalyzed by using the research analysis system RAS 1,000
the V1 and V2 receptors were quantitated by inftracting the nonspecific binding (incubatedwith OPC-21268 and OPC-31260, respectively) from the total binding. To assess a more precise localization of the V1and V2 receptors, we also investigated the micro-ARG of the renal V1 and V2 receptorsby dipping the kidney section slides used for macro-ARG into a photographic emulsion and observing the receptors under light microscopy. [3H]-VP binding to the rat kidney was completely displaced by unlabeled excess VP, but not by unlabeled angiotensin II, indicating that [3H]-VP binding was specific for VP receptors. Computerized quantification showed that V2 receptors, visualized by OPC-31260, were the predominant type of VP receptor in the kidney. Conversely, V1receptors, visualized by OPC-21268, werefewer in number. V) receptors were partly localized to the glomerulus, cortical vessels, interstitial cells, and the medullary vessels. The V2receptors localized to the collecting ducts and medullary tubules. Our findings indicated that renal V1 and V2 receptors can be detected by in vitro macro- and micro-ARG by using OPC-21268 and OPC-31260. © 1997 S.Karger AG, Basel.

DOI： 10.1159/000190200

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Language：English  

We previously examined the precise localization of vasopressin (VP) V1 and V2 receptors in the rat kidney using in vitro macro- and micro- autoradiography (ARG), and established the methodology of quantification for macro-ARG. In this study, to elucidate the role of VP in hypertension, we investigated the change within V1 and V2 receptors in the kidney of spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)- salt hypertensive rats at different hypertensive stages. In SHR, although medullary V1 and V2 receptors decreased compared with age-matched Wistar- Kyoto (WKY) rats at the developmental hypertensive stage, these receptors increased once hypertension was established. Conversely, in DOCA-salt hypertensive rats, both renal V1 and V2 receptors decreased with elevated blood pressure. Therefore, expression of renal V1 and V2 receptors proved to be different between two models of hypertension, SHR and DOCA-salt hypertensive rats, when their blood pressure increases. In DOCA-salt hypertensive rats, renal V1 and V2 receptors may be down-regulated secondary to the high blood VP level. In SHR, the increase in renal V1 and V2 receptors may have a role in the development of high blood pressure in this strain of rats.

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Language：English  

A 38-year-old woman was hospitalized in January, 1994 with renal dysfunction and hypercalcemia. Before admission, she was diagnosed as having urolithiasis, and had been treated twice with extracorporeal shock wave lithotripsy (ESWL). Ophthalmologically, she exhibited iritis and secondary glaucoma. Hypercalcemia, an extremely low titer of parathyroid hormone (PTH), and elevation of angiotensin-converting enzyme (ACE) and lysozyme activity were noted. These findings suggested sarcoidosis, although the chest X-ray showed only fibrotic changes. Hypercalcemia was suspected of having been caused secondarily by sarcoidosis. Since her laboratory data also showed renal dysfunction and abnormal unnalysis, a renal biopsy was performed. The histological findings indicated a tubular and interstitial disorder without glomerular abnormality
calcium deposition, which was detected by X-ray energy dispersive analysis, was observed in the tubular cytoplasm. Administration of prednisolone alleviated the renal dysfunction and decreased the elevation of ACE activity and lysozyme level of the blood. Sarcoidosis is sometimes associated with hypercalcemia, but rarely with renal dysfunction. These findings suggested that sarcoidosis may be associated with renal dysfunction due to tubular injury caused by calcium deposition in the tubules, and that glucocorticoid therapy was effective for these disorders.

DOI： 10.14842/jpnjnephrol1959.38.141

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Language：English  

A 38-year-old woman was hospitalized in January, 1994 with renal dysfunction and hypercalcemia. Before admission, she was diagnosed as having urolithiasis, and had been treated twice with extracorporeal shock wave lithotripsy (ESWL). Ophthalmologically, she exhibited iritis and secondary glaucoma. Hypercalcemia, an extremely low titer of parathyroid hormone (PTH), and elevation of angiotensin-converting enzyme (ACE) and lysozyme activity were noted. These findings suggested sarcoidosis, although the chest X-ray showed only fibrotic changes. Hypercalcemia was suspected of having been caused secondarily by sarcoidosis. Since her laboratory data also showed renal dysfunction and abnormal unnalysis, a renal biopsy was performed. The histological findings indicated a tubular and interstitial disorder without glomerular abnormality
calcium deposition, which was detected by X-ray energy dispersive analysis, was observed in the tubular cytoplasm. Administration of prednisolone alleviated the renal dysfunction and decreased the elevation of ACE activity and lysozyme level of the blood. Sarcoidosis is sometimes associated with hypercalcemia, but rarely with renal dysfunction. These findings suggested that sarcoidosis may be associated with renal dysfunction due to tubular injury caused by calcium deposition in the tubules, and that glucocorticoid therapy was effective for these disorders.

DOI： 10.14842/jpnjnephrol1959.38.141

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Language：English   Publisher：Okayama University Medical School  

DOI： 10.18926/AMO/30375

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Language：English   Publisher：Okayama University Medical School  

DOI： 10.18926/AMO/30375

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