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

BACKGROUND: The relationship between the major periodontal bacteria, Porphyromonas gingivalis, and the pathogenesis of IgA nephropathy (IgAN)-particularly with respect to galactose-deficient IgA1 (Gd-IgA1)-has not been fully elucidated. METHODS: Saliva samples from 30 IgAN patients and 44 patients with chronic kidney disease (CKD) were subjected to analysis of P. gingivalis status via polymerase chain reaction using a set of P. gingivalis-specific primers. The associations between P. gingivalis presence and clinical parameters, including plasma Gd-IgA1, were analyzed in each group. RESULTS: Compared with the CKD group, the IgAN group demonstrated significantly higher plasma Gd-IgA1 levels (p < 0.05). Compared with the P. gingivalis-negative subgroup, the P. gingivalis-positive subgroup exhibited significantly higher plasma Gd-IgA1 levels in both IgAN and CKD patients (p < 0.05). Additionally, among IgAN patients, the P. gingivalis-positive subgroup displayed significantly higher plasma Gd-IgA1 and urine protein levels, compared with the P. gingivalis-negative subgroup (p < 0.05). With respect to renal biopsy findings, the frequencies of segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis were significantly greater in the P. gingivalis-positive subgroup than in the P. gingivalis-negative subgroup, according to the Oxford classification of IgAN (p < 0.05). CONCLUSION: Our findings suggest an association between the presence of P. gingivalis in the oral cavity and the pathogenesis of IgAN, mediated by increased levels of Gd-IgA1.

DOI： 10.1007/s10157-023-02411-4

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Hydroxyapatite adsorbs various substances, but little is known about the effects on oral bacteria of adsorption onto hydroxyapatite derived from scallop shells. In the present study, we analyzed the effects of adsorption of Streptococcus mutans onto scallop-derived hydroxyapatite. When scallop-derived hydroxyapatite was mixed with S. mutans, a high proportion of the bacterial cells adsorbed onto the hydroxyapatite in a time-dependent manner. An RNA sequencing analysis of S. mutans adsorbed onto hydroxyapatite showed that the upregulation of genes resulted in abnormalities in pathways involved in glycogen and histidine metabolism and biosynthesis compared with cells in the absence of hydroxyapatite. S. mutans adsorbed onto hydroxyapatite was not killed, but the growth of the bacteria was inhibited. Electron microscopy showed morphological changes in S. mutans cells adsorbed onto hydroxyapatite. Our results suggest that hydroxyapatite derived from scallop shells showed a high adsorption ability for S. mutans. This hydroxyapatite also caused changes in gene expression related to the metabolic and biosynthetic processes, including the glycogen and histidine of S. mutans, which may result in a morphological change in the surface layer and the inhibition of the growth of the bacteria.

DOI： 10.3390/ijms241411371

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

DOI： 10.1016/j.pdj.2023.06.004

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Previous research has demonstrated that Porphyromonas gulae (P. gulae) significantly contributes to the development of periodontal disease in dogs. Porphyromonas gulae is divided into three subtypes according to the 41-kDa filamentous appendage (fimA), defined as types A, B, and C. This study aimed to elucidate the association between fimA type of P. gulae with the number of permanent teeth, reflecting the severity of periodontal disease. Two hundred twenty-five dogs were categorized by P. gulae fimA type as negative, type A dominant, type B dominant, and type C dominant. The stage of periodontal disease in P. gulae-positive dogs increased with age, particularly in type C dominant dogs. Correspondingly, the number of permanent teeth in P. gulae fimA type C-dominant dogs was significantly lower than that of P. gulae-negative dogs, suggesting there is a significant association between fimA type of P. gulae and the number of permanent teeth resulting from the development of periodontal disease.

DOI： 10.3389/fvets.2023.1022838

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The presence of Streptococcus mutans expressing Cnm protein encoded by cnm (cnm-positive S. mutans) in the oral cavity is associated with immunoglobulin A (IgA) nephropathy (IgAN). However, the precise mechanism by which cnm-positive S. mutans is involved in the pathogenesis of IgAN remains unclear. The present study evaluated glomerular galactose-deficient IgA1 (Gd-IgA1) to clarify the association between the presence of cnm-positive S. mutans and glomerular Gd-IgA1 in patients with IgAN. The presence of S. mutans and cnm-positive S. mutans was evaluated by polymerase chain reaction in saliva specimens from 74 patients with IgAN or IgA vasculitis. Immunofluorescent staining of IgA and Gd-IgA1 using KM55 antibody in clinical glomerular tissues was then performed. There was no significant association between the glomerular staining intensity of IgA and the positive rate of S. mutans. However, there was a significant association between the glomerular staining intensity of IgA and the positive rate of cnm-positive S. mutans (P < 0.05). There was also a significant association between the glomerular staining intensity of Gd-IgA1 (KM55) and the positive rate of cnm-positive S. mutans (P < 0.05). The glomerular staining intensity of Gd-IgA1 (KM55) was not associated with the positive rate of S. mutans. These results suggest that cnm-positive S. mutans in the oral cavity is associated with the pathogenesis of Gd-IgA1 in patients with IgAN.

DOI： 10.1371/journal.pone.0282367

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Periodontopathic bacteria cause an inflammatory disease localized in the periodontal tissue and are associated with various conditions in other body parts. The distribution of periodontopathic bacterial species in the tonsils is unknown, even though the tonsils are located close to the oral cavity, and inflammation of the tonsils causes various systemic diseases. We detected the major periodontopathic bacterial species residing in saliva and tonsil specimens from 25 subjects undergoing tonsillectomy. Nine of the ten major periodontopathic bacterial species were detected by polymerase chain reaction of tonsil specimens, among which Campylobacter rectus was the most common (80.0%), followed by Porphyromonas gingivalis (36.0%). The other seven types of periodontopathic bacterial species were distributed with 0% to 25.0% abundance in the tonsil specimens. C. rectus had a high detection rate in tonsil specimens (> 75.0%), regardless of whether it was detected in the corresponding saliva specimens. However, the detection rate for P. gingivalis in tonsil specimens was significantly higher in subjects with P. gingivalis-positive saliva (77.8%) than in those with P. gingivalis-negative saliva (6.3%; P < 0.001). Furthermore, 75.0% of P. gingivalis in tonsil specimens did not have the known fimA gene that encodes the 41-kDa filamentous appendage protein FimA, which is expressed on the cell surface of the bacteria. Our results suggest that certain periodontopathic bacterial species are detected in the tonsils either independently of or depending on their distribution in the oral cavity and may be involved in tonsil-related diseases.

DOI： 10.1007/s10266-022-00776-8

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Language：Japanese   Publisher：岡山歯学会  

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Language：Japanese   Publisher：岡山歯学会  

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Porphyromonas gulae is an animal-derived oral microorganisms known also to be associated with periodontal disease in humans. We previously reported that P. gulae proteases are possible one of virulence factors related to adhesion and invasion of gingival epithelial cells, and host cell destruction. Here we attempted to characterize bacterial proteases associated with P. gulae. Both alkaline phosphatase and trypsin activity were identified in all examined P. gulae strains and P. gingivalis ATCC33277. Each of the P. gulae strains also showed proteolytic activity in cell extract and/or culture supernatant samples. In addition, there was a significant increase in protease activity level seen in living bacterial cells, dependent on cell number, while there were no significant differences regarding proteolytic activity among the P. gulae strains. The present results indicate that antipain and PMSF are effective inhibitors of P. gulae proteases as well as P. gingivalis. In addition, TLCK and leupeptin significantly inhibited proteolytic activity in a dose-dependent manner. On the other hand, AEBSF, ALLN, aprotinin, bestatin, chymostatin, E64, EDTA, pepstatin, and phosphoramidon showed no inhibitory effects, while those of KYT-1 and KYT-36, P. gingivalis gingipain-specific inhibitors, were negligible. These results suggest that both P. gulae and P. gingivalis produce and secrete trypsin-like serine proteases, while the structure of those proteases differ between the two bacteria.

DOI： 10.14943/jjvr.70.3-4.79

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Streptococcus mutans, a Gram-positive facultative anaerobic bacterium, is a major pathogen of dental caries. The protein Cnm of S. mutans is involved in collagen binding, but its other biological functions are unknown. In this study, a Cnm-deficient isogenic mutant and a complementation strain were generated from a Cnm-positive S. mutans strain to help determine the properties of Cnm. Initially, comparison of the cell surface structure was performed by electron microscopy, which demonstrated that Cnm appears to be localized on the cell surface and associated with a protruding cell surface structure. Deep RNA sequencing of the strains revealed that the defect in Cnm caused upregulated expression of many genes related to ABC transporters and cell-surface proteins, while a few genes were downregulated. The amount of biofilm formed by the Cnm-defective strain increased compared with the parental and complemented strains, but the biofilm structure was thinner because of elevated expression of genes encoding glucan synthesis enzymes, leading to increased production of extracellular polysaccharides. Particular antibiotics, including bacitracin and chloramphenicol, had a lower minimum inhibitory concentration for the Cnm-defective strain than particular antibiotics, including bacitracin and chloramphenicol, compared with the parental and complemented strains. Our results suggest that S. mutans Cnm is located on the cell surface, gives rise to the observed protruding cell surface, and is associated with several biological properties related to membrane permeability.

DOI： 10.3389/fcimb.2022.994014

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BACKGROUND: The simultaneous presence of Streptococcus mutans expressing the Cnm protein encoded by cnm (i.e., cnm-positive S. mutans) and Campylobacter rectus in the oral cavity has been associated with proteinuria in patients with IgA nephropathy (IgAN). OBJECTIVES: The present study evaluated the relationship between renal function and oral bacteria in patients with IgAN over 5 years of follow-up. METHODS: The presence of C. rectus and cnm-positive S. mutans in saliva samples of 117 patients with IgAN was initially evaluated by polymerase chain reaction. Patients were then divided into four groups according to the results of C. rectus and cnm-positive S. mutans detection: group A: C. rectus (-), cnm-positive S. mutans (-); group B: C. rectus (+), cnm-positive S. mutans (-); group C: C. rectus (-), cnm-positive S. mutans (+); and group D: C. rectus (+), cnm-positive S. mutans (+). Clinical characteristics were prospectively followed for 5 years. RESULTS: Serum creatinine levels were significantly higher in group D than in group A over 5 years of follow-up. Additionally, the proportion of patients with an estimated glomerular filtration rate <45 mL/min increased over time; it was significantly greater in group D than in group A over 5 years of follow-up. CONCLUSION: These results suggest that the simultaneous presence of C. rectus and cnm-positive S. mutans in the oral cavity is associated with renal dysfunction in IgAN patients.

DOI： 10.1159/000525511

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

OBJECTIVES: To determine the anti-inflammatory effects of green tea catechins in immortalized human gingival epithelial cells (Ca9-22) stimulated with Porphyromonas gulae lipopolysaccharide (LPS). METHODS: Ca9-22 cells were incubated with P. gulae LPS (10 μg/ml) with or without green tea catechins, epigallocatechin-3-gallate (EGCg), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and epicatechin (EC) (each at 50 μM), for 6 or 24 hours. Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay were used to determine the induction of cyclooxygenase 2 (COX2), tumor necrosis factor alpha (TNF-ɑ), interleukin 6 (IL-6), and IL-8. Furthermore, the expression of toll-like receptors (TLRs) 2 and 4 was examined using real-time PCR and western blotting analysis, and phosphorylation of the p38 and ERK1/2 was examined using western blotting analysis. RESULTS: At the mRNA and protein levels, EGCg, EGC, ECG, and EC were found to significantly inhibit COX2, TNF-ɑ, IL-6, and IL-8. Furthermore, the levels of ERK1/2 and p38 phosphorylation induced by P. gulae LPS were decreased following the addition of each of the catechins, as well as TLR2 and 4 mRNA and protein. CONCLUSIONS: These findings indicate that green tea catechins are potent inhibitors of inflammatory responses induced by P. gulae LPS, and may also be useful for prevention and/or attenuation of periodontitis.

DOI： 10.1016/j.job.2022.05.006

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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A relationship between IgA nephropathy (IgAN) and bacterial infection has been suspected. As IgAN is a chronic disease, bacteria that could cause chronic infection in oral areas might be pathogenetic bacteria candidates. Oral bacterial species related to dental caries and periodontitis should be candidates because these bacteria are well known to be pathogenic in chronic dental disease. Recently, several reports have indicated that collagen-binding protein (cnm)-(+) Streptococcs mutans is relate to the incidence of IgAN and the progression of IgAN. Among periodontal bacteria, Treponema denticola, Porphyromonas gingivalis and Campylobacte rectus were found to be related to the incidence of IgAN. These bacteria can cause IgAN-like histological findings in animal models. While the connection between oral bacterial infection, such as infection with S. mutans and periodontal bacteria, and the incidence of IgAN remains unclear, these bacterial infections might cause aberrantly glycosylated IgA1 in nasopharynx-associated lymphoid tissue, which has been reported to cause IgA deposition in mesangial areas in glomeruli, probably through the alteration of microRNAs related to the expression of glycosylation enzymes. The roles of other factors related to the incidence and progression of IgA, such as genes and cigarette smoking, can also be explained from the perspective of the relationship between these factors and oral bacteria. This review summarizes the relationship between IgAN and oral bacteria, such as cnm-(+) S. mutans and periodontal bacteria.

DOI： 10.3390/ijms23020725

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DOI： 10.3390/ijms222

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IgA nephropathy (IgAN) has been considered to have a relationship with infection in the tonsil, because IgAN patients often manifest macro hematuria just after tonsillitis. In terms of oral-area infection, the red complex of periodontal bacteria (Porphyromonas gingivalis (P. gingivalis), Treponema denticol (T. denticola) and Tannerella forsythia (T. forsythia)) is important, but the relationship between these bacteria and IgAN remains unknown. In this study, the prevalence of the red complex of periodontal bacteria in tonsil was compared between IgAN and tonsillitis patients. The pathogenicity of IgAN induced by P. gingivalis was confirmed by the mice model treated with this bacterium. The prevalence of P. gingivalis and T. forsythia in IgAN patients was significantly higher than that in tonsillitis patients (p < 0.001 and p < 0.05, respectively). A total of 92% of tonsillitis patients were free from red complex bacteria, while only 48% of IgAN patients had any of these bacteria. Nasal administration of P. gingivalis in mice caused mesangial proliferation (p < 0.05 at days 28a nd 42; p < 0.01 at days 14 and 56) and IgA deposition (p < 0.001 at day 42 and 56 after administration). Scanning-electron-microscopic observation revealed that a high-density Electron-Dense Deposit was widely distributed in the mesangial region in the mice kidneys treated with P. gingivalis. These findings suggest that P. gingivalis is involved in the pathogenesis of IgAN.

DOI： 10.3390/ijms222313022

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

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DOI： 10.1038/s41598-021-9

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Autophagy-related genes (ARGs) have been implicated in the initiation and progression of malignant tumor promotion. To investigate the dynamics of expression of genes, including ARGs, head and neck squamous cell carcinoma (HNSCC) cells were placed under serum-free conditions to induce growth retardation and autophagy, and these starved cells were subjected to transcriptome analysis. Among the 21 starvation-induced genes (SIGs) located in the autophagy, cell proliferation, and survival signaling pathways, we identified SIGs that showed prominent up-regulation or down-regulation in vitro. These included AGR2, BST2, CALR, CD22, DDIT3, FOXA2, HSPA5, PIWIL4, PYCR1, SGK3, and TRIB3. The Cancer Genome Atlas (TCGA) database of HNSCC patients was used to examine the expression of up-regulated genes, and CALR, HSPA5, and TRIB3 were found to be highly expressed relative to solid normal tissue in cancer and the survival rate was reduced in patients with high expression. Protein-protein interaction analysis demonstrated the formation of a dense network of these genes. Cox regression analysis revealed that high expression of CALR, HSPA5, and TRIB3 was associated with poor prognosis in patients with TCGA-HNSCC. Therefore, these SIGs up-regulated under serum starvation may be molecular prognostic markers in HNSCC patients.

DOI： 10.1038/s41598-021-98544-1

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Objective: Porphyromonas gulae, a major periodontal pathogen in animals, possesses fimbriae that have been classified into three genotypes (A, B, C) based on the diversity of fimA genes encoding fimbrillin protein (FimA). P. gulae strains with type C fimbriae were previously shown to be more virulent than other types. In this study, we further examined the host toxicity mediated by P. gulae fimbriae by constructing recombinant FimA (rFimA) expression vectors for each genotype and raised antibodies to the purified proteins. Methods and Results: All larvae died within 204 h following infection with P. gulae type C at the low-dose infection, whereas type A and B did not. Among fimA types, the survival rates of the larvae injected with rFimA type C were remarkably decreased, while the survival rates of the larvae injected with rFimA type A and type B were greater than 50%. Clindamycin treatment inhibited the growth of type C strains in a dose-dependent manner, resulting in an increased rate of silkworm survival. Finally, type C rFimA-specific antiserum prolonged the survival of silkworm larvae stimulated by infection with P. gulae type C strain or injection of rFimA type C protein. Conclusion: These results suggested that type C fimbriae have high potential for enhancement of bacterial pathogenesis, and that both clindamycin and anti-type C rFimA-specific antibodies are potent inhibitors of type C fimbriae-induced toxicity. This is the first report to establish a silkworm infection model using P. gulae for toxicity assessment.

DOI： 10.1080/20002297.2021.1914499

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OBJECTVES: Citrus unshiu has been shown to exhibit antimicrobial effects against citrus diseases. In the present study, C. unshiu was divided into flavedo, albedo, fruits, and leaves; the inhibitory effects of these extracts on Streptococcus mutans, a major pathogen of dental caries, were investigated. DESIGN: C. unshiu specimens were separated into flavedo, albedo, fruits, and leaves. First, pH values and polyphenol amounts in Citrus extracts were measured. In addition, Citrus extract was added to the bacterial suspensions of S. mutans MT8148, and inhibitory effects of C. unshiu extracts on MT8148 for antimicrobial activity, bacterial growth, and biofilm formation were analyzed. These assays were also performed using C. sinensis extracts. RESULTS: Among these extracts, albedo exhibited a pH value closest to neutral, while the fruits exhibited the most acidic pH value; the pH values significantly differed between these extracts (P < 0.05). In addition, the amounts of polyphenols were significantly higher in albedo than in other extracts (P < 0.001). All extracts showed inhibitory effects on MT8148 for antimicrobial activity, bacterial growth and biofilm formation. These inhibitory effects were significantly stronger in flavedo, albedo, and fruits, compared with leaves (P < 0.05). Furthermore, extracts of Citrus sinensis also showed inhibitory effects on S. mutans, although these effects were weaker than the effects of C. unshiu. CONCLUSION: These results suggest that extracts from C. unshiu fruits exhibit inhibitory effects on S. mutans, among which albedo may be especially useful for dental caries prevention due to its neutral pH and abundant polyphenols, in addition to its inhibitory effects.

DOI： 10.1016/j.archoralbio.2021.105056

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

The mechanisms underlying immunoglobulin A nephropathy (IgAN), the most common chronic form of primary glomerulonephritis, remain poorly understood. Streptococcus mutans, a Gram-positive facultatively anaerobic oral bacterium, is a common cause of dental caries. In previous studies, S. mutans isolates that express Cnm protein on their cell surface were frequently detected in IgAN patients. In the present study, inoculation of Cnm-positive S. mutans in the oral cavities of 2-week-old specific-pathogen free Sprague-Dawley rats fed a high-sucrose diet for 32 weeks produced severe dental caries in all rats. Immunohistochemical analyses of the kidneys using IgA- and complement C3-specific antibodies revealed positive staining in the mesangial region. Scanning electron microscopy revealed a wide distribution of electron dense deposits in the mesangial region and periodic acid-Schiff staining demonstrated prominent proliferation of mesangial cells and mesangial matrix. These results suggest that IgAN-like glomerulonephritis was induced in rats with severe dental caries by Cnm-positive S. mutans.

DOI： 10.1038/s41598-021-85196-4

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Porphyromonas gulae, an animal-derived periodontal pathogen, expresses several virulence factors, including fimbria, lipopolysaccharide (LPS), and proteases. We previously reported that its invasive efficiency was dependent on fimbriae types. In addition, P. gulae LPS increased inflammatory responses via toll-like receptors. The present study was conducted to investigate the involvement of P. gulae proteases in bacterial and host cell biology. P. gulae strains showed an ability to agglutinate mouse erythrocytes and also demonstrated coaggregation with Actinomyces viscosus, while the protease inhibitors antipain, PMSF, TLCK, and leupeptin diminished P. gulae proteolytic activity, resulting in inhibition of hemagglutination and coaggregation with A. viscosus. In addition, specific proteinase inhibitors were found to reduce bacterial cell growth. P. gulae inhibited Ca9-22 cell proliferation in a multiplicity of infection- and time-dependent manner. Additionally, P. gulae-induced decreases in cell contact and adhesion-related proteins were accompanied by a marked change in cell morphology from well spread to rounded. In contrast, inhibition of protease activity prevented degradation of proteins, such as E-cadherin, β-catenin, and focal adhesion kinase, and also blocked inhibition of cell proliferation. Together, these results indicate suppression of the amount of human proteins, such as γ-globulin, fibrinogen and fibronectin, by P. gulae proteases, suggesting that a novel protease complex contributes to bacterial virulence. This article is protected by copyright. All rights reserved.

DOI： 10.1111/cmi.13312

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Porphyromonas gulae, a Gram-negative black-pigmented anaerobe, has been associated with periodontal disease in companion animals and its virulence has been attributed to various factors, including lipopolysaccharide (LPS), protease and fimbriae. Toll-like receptors (TLRs) recognise pathogen-associated molecular patterns, such as peptidoglycan, lipids, lipoproteins, nucleic acid and LPS. Following P. gulae infection, some inflammatory responses are dependent on both TLR2 and TLR4. In addition, a recent clinical study revealed that acute and persistent inflammatory responses enhance the expressions of TLR2 and TLR4 in the oral cavity. In this study, we investigated the interaction between P. gulae LPS and human gingivalis epithelial cells (Ca9-22 cells). P. gulae LPS was found to increase TLR2 and TLR4 mRNA expressions and protein productions, and enhanced inflammatory responses, such as COX2 , TNF-ɑ, IL-6 and IL-8. Stimulated Ca9-22 cells exhibited phosphorylation of ERK1/2 and p38, and their inhibitors diminished inflammatory responses, while knockdown of the TLR2 and/or TLR4 genes with small interfering RNA (siRNA) prevented inflammatory responses. Moreover, p38 and ERK1/2 phosphorylation was decreased in TLR2 and TLR4 gene knockdown cells. These findings suggest that P. gulae LPS activates p38 and ERK1/2 via TLR2 and TLR4, leading to inflammatory responses in human gingival epithelial cells.

DOI： 10.1111/cmi.13254

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BACKGROUND: IgA nephropathy (IgAN) is one of the most frequently occurring types of chronic glomerulonephritis. Previous analyses have revealed that a major pathogen of dental caries, Streptococcus mutans [which expresses collagen-binding protein (Cnm) on its surface], is involved in the pathogenesis of IgAN. METHODS: Cnm-positive S. mutans isolated from a patient with IgAN was intravenously administered to specific pathogen-free Sprague-Dawley rats to evaluate their kidney conditions. RESULTS: The urinary protein level of the S. mutans group reached a plateau at 30 days, with increased numbers of mesangial cells and an increased mesangial matrix. The numbers of rats with IgA-positive and/or C3-positive glomeruli were significantly greater in the S. mutans group than in the control group at 45 days (P < 0.05). Electron microscopy analyses revealed electron-dense depositions in the mesangial area among rats in the S. mutans group. There were significantly more CD68-positive cells (macrophages) in the glomeruli of the S. mutans group than in the glomeruli of the control group during the late phase (P < 0.05), similar to the findings in patients with IgAN. CONCLUSION: Our results suggested that intravenous administration of Cnm-positive S. mutans caused transient induction of IgAN-like lesions in rats.

DOI： 10.1007/s10157-020-01961-1

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Streptococcus mutans, a significant contributor to dental caries, is occasionally isolated from the blood of patients with infective endocarditis. We previously showed that S. mutans strains expressing collagen-binding protein (Cnm) are present in the oral cavity of approximately 10-20% of humans and that they can effectively invade human umbilical vein endothelial cells (HUVECs). Here, we investigated the potential molecular mechanisms of HUVEC invasion by Cnm-positive S. mutans. The ability of Cnm-positive S. mutans to invade HUVECs was significantly increased by the presence of serum, purified type IV collagen, and fibrinogen (p < 0.001). Microarray analyses of HUVECs infected by Cnm-positive or -negative S. mutans strains identified several transcripts that were differentially upregulated during invasion, including those encoding the small G protein regulatory proteins ARHGEF38 and ARHGAP9. Upregulation of these proteins occurred during invasion only in the presence of serum. Knockdown of ARHGEF38 strongly reduced HUVEC invasion by Cnm-positive S. mutans. In a rat model of infective endocarditis, cardiac endothelial cell damage was more prominent following infection with a Cnm-positive strain compared with a Cnm-negative strain. These results suggest that the type IV collagen-Cnm-ARHGEF38 pathway may play a crucial role in the pathogenesis of infective endocarditis.

DOI： 10.1038/s41598-020-75933-6

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

DOI： 10.1080/20002297.202

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Background: Streptococcus mutans, a biofilm-forming bacterium, possesses several transporters that function as import/export molecules. Among them, the PII protein family is composed of members that regulate glutamine synthesis in bacterial species. Objective: In this study, we characterized the function of the glutamine transporter in S. mutans MT8148. Methods: The SMU.732 gene, corresponding to glnP in S. mutans, is homologous to the glutamine transporter gene in Bacillus subtilis. We constructed a glnP-inactivated mutant strain (GEMR) and a complement strain (comp-GEMR) and evaluated their biological functions. Results: Growth of GEMR was similar in the presence and absence of glutamine, whereas the growth rates of MT8148 and comp-GEMR were significantly lower in the presence of glutamine as compared to its absence. Furthermore, biofilms formed by MT8148 and comp-GEMR were significantly thicker than that formed by GEMR, while the GEMR strain showed a significantly lower survival rate in an acidic environment than the other strains. Addition of n-phenyl-2-naphthylamine, used to label of the membrane, led to increased fluorescence intensity of MT8148 and GEMR, albeit that was significantly lower in the latter. Conclusions: These results suggest that glnP is associated with glutamine transport in S. mutans, especially the import of glutamine involved in biofilm formation.

DOI： 10.1080/20002297.2020.1797320

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

DOI： 10.1038/s41598-020-63861-4

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Mouth rinses are a useful supplementary tool for the prevention of oral infectious diseases. Although the antimicrobial effects of mouth rinses have been investigated, there are few studies focusing on the comparison of the effects among various oral bacterial species. In the present study, the inhibitory effect of a commercial mouth rinse, "ConCoolF," and each of its major components, chlorhexidine gluconate, ethanol, and green tea extract, on multiple species of oral bacteria were investigated. Inhibition of bacterial growth was observed in all cariogenic streptococcal species with different genera, serotypes, and strains isolated from different countries when either the complete mouth rinse or chlorhexidine gluconate were used. However, no growth inhibition was observed when the bacteria were exposed to ethanol or green tea extract. Interestingly, growth inhibition was greatly reduced in non-cariogenic streptococci compared with cariogenic streptococci. In addition, both the mouth rinse and chlorhexidine gluconate inhibited the biofilms formed by both Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis), among which the inhibitory effect against S. mutans was higher than that against P. gingivalis. These results suggest that a mouth rinse containing chlorhexidine gluconate, ethanol, and green tea extract, or chlorhexidine gluconate alone, exhibits antimicrobial activity against several oral bacteria species, having greater activity against pathogenic bacteria.

DOI： 10.2334/josnusd.18-0483

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Porphyromonas gulae is a major periodontal pathogen in dogs, which can be transmitted to their owners. A major virulence factor of P. gulae consists of a 41-kDa filamentous appendage (FimA) on the cell surface, which is classified into three genotypes: A, B, and C. Thus far, inhibition of periodontal disease in dogs remains difficult. The present study assessed the inhibitory effects of a combination of clindamycin and interferon alpha (IFN-α) formulation against P. gulae and periodontal disease. Growth of P. gulae was significantly inhibited by clindamycin; this inhibition had a greater effect on type C P. gulae than on type A and B isolates. In contrast, the IFN-α formulation inhibited the expression of IL-1β and COX-2 elicited by type A and B isolates, but not that elicited by type C isolates. Furthermore, periodontal recovery was promoted by the administration of both clindamycin and IFN-α formulation to dogs undergoing periodontal treatment; moreover, this combined treatment reduced the number of FimA genotypes in oral specimens from treated dogs. These results suggest that a combination of clindamycin and IFN-α formulation inhibit P. gulae virulence and thus may be effective for the prevention of periodontal disease induced by P. gulae.

DOI： 10.1038/s41598-020-59730-9

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Oral lactobacilli are members of a group of bacteria implicated in caries progression, although information regarding their transmission, colonization, and caries-associated species is not well established. This study isolated oral lactobacilli from a group of children with primary dentition for determination of Lactobacillus prevalence, detection of Streptococcus mutans, a major pathogen of caries initiation, and dental caries status of the children. Species of Lactobacillus isolates were determined from examination of 16S rDNA sequences. Subsequently, the most prevalent species was evaluated for involvement in caries status, and binding ability to type I collagen of all Lactobacillus isolates was determined in association with caries status. Multilocus sequence typing (MLST) of eleven loci was carried out to study strains of the predominant Lactobacillus sp. The detection of oral lactobacilli together with S. mutans was significantly associated with the highest dental caries indices, but there was no involvement of collagen-binding properties of Lactobacillus isolates in caries status. Lactobacillus fermentum was the most prevalent, and its presence was related to high scores of caries indices. MLST analysis of L. fermentum population could not specify a particular clone associated with caries status, but revealed sharing of identical L. fermentum strains among children in the same classrooms. Taken together, the data contributed useful information on the role of oral lactobacilli, in particular L. fermentum in dental caries.

DOI： 10.1159/000506468

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Authorship：Corresponding author   Language：English  

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER  

Early onset periodontitis is rarely seen in infants, though often leads to an acute and serious clinical course when encountered in such patients. Autoimmune neutropenia presents systemic and dental symptoms, as depressed resistance to bacterial infection is caused by a disorder that reduces the number of neutrophils. This disease can result in not only gingival inflammation but also destruction of periodontal tissues, such as attachment loss, alveolar bone absorption, and early tooth loss in primary as well as mixed dentition. Here, we report treatment of a child with marginal periodontitis from the age of 3 years-7 years 9 months. No systemic manifestations were noted until 3 years of age, thus the patient had never received a detailed examination or medication related to the disease. Following examinations at our department, we referred the patient to a pediatrician at our university hospital for possible systemic disease, who made a diagnosis of autoimmune neutropenia. Although administration of antibiotics and professional dental care were continued, neutrophil count was not increased and progressive periodontal destruction was observed. Extraction of teeth with poor prognosis was performed and a prosthetic strategy for the missing teeth developed. It is important to recognize that periodontitis along with autoimmune neutropenia can appear in infants, even though the incidence is quite low. Early detection and early treatment of this disease is necessary for delaying progression of periodontitis and optimal occlusal induction of permanent teeth. (C) 2019 Japanese Society of Pediatric Dentistry. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.pdj.2019.06.002

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DOI： 10.1038/s41598-019-56679-2

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Other Link： http://www.nature.com/articles/s41598-019-56679-2

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

Porphyromonas gulae, a Gram-negative black-pigmented anaerobe, is one of several major periodontal pathogens of animals. P. gulae isolates from dogs have been classified into three genotypes based on a 41-kDa filamentous appendage (FimA) on the cell surface, which is closely related to virulence in periodontal disease. However, other specific bacterial virulence factors contributing to the aggravation of periodontal disease in cats remain elusive. In the present study, we assessed FimA diversity in P. gulae isolates from cats and examined whether this diversity influenced periodontal condition. The putative amino acid sequences of FimA from 15 P. gulae isolates from 13 cats were classified into three genotypes (types A, B, and C), which showed 95-100% identity and similarity to the fimA types in dogs. The type C isolate showed greater adhesion and invasion properties in periodontal ligament fibroblasts as well as stronger inhibition of scratch closure of the cells compared with type A and B isolates. Next, a PCR-based method for identification of fimA genotype was developed and used to analyze 99 oral swab specimens from cats. High fimA type A detection rates were observed regardless of the periodontal condition, whereas types B and C were frequently detected from subjects with moderate and severe periodontitis, respectively. These results suggest that P. gulae isolates from cats can be classified into three types based on fimA genotype, which may be closely related to virulence in periodontitis.

DOI： 10.1016/j.vetmic.2018.12.018

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Porphyromonas gulae, an animal periodontal pathogen, possess fimbriae classified into three genotypes (A-C) based on the diversity of fimA genes encoding FimA. Accumulating evidence suggests that P. gulae strains with type C fimbriae are more virulent as compared to those with other types. The ability of these organisms to adhere to and invade gingival epithelial cells has yet to be examined. P. gulae showed the greatest levels of adhesion and invasion at a multiplicity of infection of 100 for 90 min. P. gulae type C and some type B strains invaded gingival epithelial cells at significantly greater levels than the other strains, at the same level of efficiency as P. gingivalis with type II fimbriae. Adhesion and invasion of gingival epithelial cells by P. gulae were inhibited by cytochalasin D and sodium azide, indicating the requirements of actin polymerization and energy metabolism for those activities. Invasion within gingival epithelial cells was blocked by staurosporine, whereas those inhibitors showed little effects on adhesion, while nocodazole and cycloheximide had negligible effects on either adhesion or invasion. P. gulae proteases were found to be essential for adhesion and invasion of gingival epithelial cells, while its DNA and RNA, and protein synthesis were unnecessary for those activities. Additionally, α5β1 integrin antibodies significantly inhibited adhesion and invasion by P. gulae. This is the first report to characterize P. gulae adhesion and invasion of human gingival epithelial cells.

DOI： 10.1371/journal.pone.0213309

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Background: Non-alcoholic steatohepatitis (NASH) is a severe state of non-alcoholic fatty liver disease (NAFLD), which is pathologically characterised by steatosis, hepatocyte ballooning, and lobular inflammation. Host-microbial interaction has gained attention as one of the risk factors for NASH. Recently, cnm-gene positive Streptococcus mutans expressing cell surface collagen-binding protein, Cnm (cnm-positive S. mutans), was shown to aggravate NASH in model mice. Here, we assessed the detection rate of cnm-positive S. mutans in oral samples from patients with NASH among NAFLD. Methods: This single hospital cohort study included 41 patients with NAFLD. NASH was diagnosed histologically or by clinical score. The prevalence of cnm-positive S. mutans, oral hygiene and blood tests, including liver enzymes, adipocytokines and inflammatory and fibrosis markers, were assessed in biopsy-proven or clinically suspected NASH among NAFLD. Results: Prevalence of cnm-positive S. mutans was significantly higher in patients with NASH than patients without NASH (OR 3.8; 95% CI 1.02 to 15.5). The cnm-positive S. mutans was related to decreased numbers of naturally remaining teeth and increased type IV collagen 7S level (median (IQR) 10.0 (5.0-17.5) vs 20.0 (5.0-25.0), p=0.06; 5.1 (4.0-7.9) vs 4.4 (3.7-5.3), p=0.13, respectively). Conclusions: Prevalence of cnm-positive S. mutans in the oral cavity could be related to fibrosis of NASH among NAFLD.

DOI： 10.1136/bmjgast-2019-000329

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Impacted primary teeth can be caused by odontogenic tumors such as odontomas, cystic diseases such as dentigerous and eruption cysts, and fibrous hyperplasia of the gingiva, while elimination of those causes reportedly results in normal eruption of primary teeth. We describe the course of a child from the age of 1 year until 4 years 10 months who had primary tooth eruption failure and was treated with dental methods. Although primary teeth expected to spontaneously erupt were followed, there were several on the left side that remained unerupted. We performed a left maxillary and mandibular gingivectomy to closely examine the cause of eruption delay and tooth germ dislocation, as well as attempt to induce eruption of the primary teeth. Based on histopathological results, the diagnosis was fibroma. Surgical procedures did not result in clear improvement of eruption failure. In order to improve masticatory function and aesthetics, the child was fixed with an artificial denture for all primary teeth not expected to erupt. (C) 2018 Japanese Society of Pediatric Dentistry. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.pdj.2018.09.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Background: Periodontitis-related pathogens, such as Campylobacter or Treponema species, have recently been shown to be associated with immunoglobulin A nephropathy (IgAN). Some strains of Streptococcus mutans, a major pathogen of dental caries, harbour the cnm gene that encodes a collagen-binding protein (Cnm). This has also been demonstrated to be associated with urinary protein levels in IgAN patients. Objectives: The purpose of the present study was to analyse the association of IgAN with C. rectus, Treponema denticola and cnm-positive S. mutans in the oral cavity of humans. Methods: The presence of C. rectus, T. denticola and cnm-positive S. mutans strains in saliva samples of 117 IgAN patients and 56 healthy controls was evaluated by PCR, and the subjects' clinical parameters were analysed. Results: C. rectus was significantly more prevalent in the IgAN group than in the control group (p &lt
0.05). The C. rectus-positive group was significantly associated with proteinuria in the IgAN group (p &lt
0.05). In addition, the C. rectus-positive and cnm-positive S. mutans group was shown to be more closely associated with urinary protein levels than the other groups (p &lt
0.0083). Conclusion: Our results suggest that harbouring C. rectus in the oral cavity could be associated with proteinuria in IgAN patients.

DOI： 10.1159/000487103

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Society for Microbiology  

Porphyromonas gingivalis, a periodontal pathogen, has been implicated as a causative agent of preterm delivery of low-birth-weight infants. We previously reported that P. gingivalis activated cellular DNA damage signaling pathways and ERK1/2 that lead to G1 arrest and apoptosis in extravillous trophoblast cells (HTR-8 cells) derived from the human placenta. In the present study, we further examined alternative signaling pathways mediating cellular damage caused by P. gingivalis. P. gingivalis infection of HTR-8 cells induced phosphorylation of p38 and Jun N-terminal protein kinase (JNK), while their inhibitors diminished both G1 arrest and apoptosis. In addition, heat shock protein 27 (HSP27) was phosphorylated through both p38 and JNK, and knockdown of HSP27 with small interfering RNA (siRNA) prevented both G1 arrest and apoptosis. Furthermore, regulation of G1 arrest and apoptosis was associated with p21 expression. HTR-8 cells infected with P. gingivalis exhibited upregulation of p21, which was regulated by p53 and HSP27. These results suggest that P. gingivalis induces G1 arrest and apoptosis via novel molecular pathways that involve p38 and JNK with its downstream effectors in human trophoblasts.

DOI： 10.1128/IAI.00923-17

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Streptococcus mutans, a major pathogen of dental caries, can cause infective endocarditis after invading the bloodstream. Recently, intravenous administration of specific S. mutans strains was shown to aggravate non-alcoholic steatohepatitis (NASH) in a mouse model fed a high-fat diet. Here, we investigated the mechanism of this aggravation in a NASH mouse model by focusing on the S. mutans cell surface collagen-binding protein (Cnm) and the 190-kDa protein antigen (PA). Mice that were intravenously administered a S. mutans strain with a defect in Cnm (TW871CND) or PA (TW871PD) did not show clinical or histopathological signs of NASH aggravation, in contrast to those administered the parent strain TW871. The immunochemical analyses demonstrated higher levels of interferon-gamma and metallothionein expression in the TW871 group than in the TW871CND and TW871PD groups. Analysis of bacterial affinity to cultured hepatic cells in the presence of unsaturated fatty acids revealed that the incorporation rate of TW871 was significantly higher than those of TW871CND and TW871PD. Together, our results suggest that Cnm and PA are important cell surface proteins for the NASH aggravation caused by S. mutans adhesion and affinity for hepatic cells.

DOI： 10.1038/srep36886

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ACAD PERIODONTOLOGY  

Background: Recent epidemiologic studies have revealed a significant association between periodontitis and oral squamous cell carcinoma (OSCC). Furthermore, periodontitis is markedly associated with orodigestive cancer mortality, whereas Porphyromonas gingivalis (Pg) infection has been identified as a specific and potentially independent microbial factor related to increased risk of orodigestive cancer death. The authors previously reported that Pg induced the precursor form of matrix metalloproteinase-9 (proMMP-9) production via proteinase-activated receptor (PAR)-related pathways, after which proMMP-9 was activated by gingipains to enhance cellular invasion of SAS cells. In the present study, effects of selected polyphenols as inhibitors of cellular invasion caused by Pg gingipains in SAS cells are examined.
Methods: OSCC cells were infected with Pg strains including gingipain mutants. To evaluate effects of inhibitors: 1) apple polyphenol (AP); 2) hop bract polyphenol (HBP); 3) high-molecular-weight fractions of HBP (HMW-HBP); 4) low-molecular-weight fractions of HBP (LMW-HBP); 5) epigallocatechin gallate (EGCg); 6) KYT-1 (Arg-gingipain inhibitor); and KYT-36 (Lys-gingipain inhibitor) in combination are used. PAR2 and PAR4 mRNA expressions are examined using real-time reverse transcription polymerase chain reaction, and signaling pathways are evaluated by western blotting analysis.
Results: KYT-1/KYT-36, AP, HBP, and HMW-HBP significantly inhibited PAR2 and PAR4 mRNA expressions, proMMP-9 activation, and cellular invasion. Furthermore, AP, HBP, and HMW-HBP reduced activation of heat shock protein 27 and Ets1 and nuclear translocation of nuclear factor-kappa B, whereas EGCg and LMW-HBP did not.
Conclusion: These results suggest that AP, HBP, HMW-HBP are potent inhibitors of proMMP-9 activation and cellular invasion mediated with Pg in OSCC cells.

DOI： 10.1902/jop.2016.160047

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

Aims: Streptococcus mutans produces multiple glucan-binding proteins (Gbps), among which GbpC encoded by the gbpC gene is known to be a cell-surface-associated protein involved in dextran-induced aggregation. The purpose of the present study was to characterize the dextran-binding domain of GbpC using bioinformatics analysis and molecular techniques.
Methods and Results: Bioinformatics analysis specified five possible regions containing molecular binding sites termed GB1 through GB5. Next, truncated recombinant GbpC (rGbpC) encoding each region was produced using a protein expression vector and five deletion mutant strains were generated, termed CDGB1 through CDGB5 respectively. The dextran-binding rates of truncated rGbpC that included the GB1, GB3, GB4 and GB5 regions in the upstream sequences were higher than that of the construct containing GB2 in the downstream region. In addition, the rates of dextran-binding for strains CDGB4 and CD1, which was entire gbpC deletion mutant, were significantly lower than for the other strains, while those of all other deletion mutants were quite similar to that of the parental strain MT8148. Biofilm structures formed by CDGB4 and CD1 were not as pronounced as that of MT8148, while those formed by other strains had greater density as compared to that of CD1.
Conclusion: Our results suggest that the dextran-binding domain may be located in the GB4 region in the interior of the gbpC gene.
Significance and Impact of the Study: Bioinformatics analysis is useful for determination of functional domains in many bacterial species.

DOI： 10.1111/jam.12895

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Porphyromonas gulae, a suspected pathogen for periodontal disease in dogs, possesses approximately 41-kDa fimbriae (FimA) that are encoded by the fimA gene. In the present study, the association of fimA genotypes with mitral regurgitation (MR) was investigated. Twenty-five dogs diagnosed with MR (age range 6-13 years old, average 10.8 years) and 32 healthy dogs (8-15 years old, average 10.8 years) were selected at the participating clinics in a consecutive manner during the same time period. Oral swab specimens were collected from the dogs and bacterial DNA was extracted, then polymerase chain reaction analysis was performed using primers specific for each fimA genotype, with the dominant genotype determined. The rate for genotype C dominant specimens was 48.0% in the MR group, which was significantly higher than that in the control group (18.8%) (P &lt;0.05). These results suggest that P. gulae fimA genotype C is associated with MR. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.rvsc.2015.07.009

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Glucan-binding proteins (Gbps) of Streptococcus mutans, a major pathogen of dental caries, mediate the binding of glucans synthesized from sucrose by the action of glucosyltransferases (GTFs) encoded by gtfB, gtfC, and gtfD. Several stress proteins, including DnaK and GroEL encoded by dnaK and groEL, are related to environmental stress tolerance. The contribution of Gbp expression to biofilm formation was analyzed by focusing on the expression levels of genes encoding GTFs and stress proteins. Biofilm-forming assays were performed using GbpA-, GbpB-, and GbpC-deficient mutant strains and the parental strain MT8148. The expression levels of gtfB, gtfC, gtfD, dnaK, and groEL were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Furthermore, the structure of biofilms formed by these Gbp-deficient mutant strains was observed using confocal laser scanning microscopy (CLSM). Biofilm-forming assay findings demonstrated that the amount formed by the GbpA-deficient mutant strain (AD1) was nearly the same as that by the parental strain, while the GbpB- and GbpC-deficient mutant strains produced lower amounts than MT8148. Furthermore, RT-qPCR assay results showed that the expressions of gtfB, dnaK, and groEL in AD1 were elevated compared with MT8148. CLSM also revealed that the structure of biofilm formed by AD1 was prominently different compared with that formed by the parental strain. These results suggest that a defect in GbpA influences the expression of genes controlling biofilm formation, indicating its importance as a protein for firm and stable biofilm formation.

DOI： 10.1111/omi.12085

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER GMBH, URBAN & FISCHER VERLAG  

Streptococcus mutans, which consists of four serotypes, c, e, f, and k, possesses a 190-kDa cell surface protein antigen (PA) for initial tooth adhesion. We used Western blot analysis to determine PA expression in 750 S. mutans isolates from 150 subjects and found a significantly higher prevalence of the isolates with PA expression defects in serotypes f and k compared to serotypes c and e. Moreover, the defect patterns could be classified into three types; no PA expression on whole bacterial cells and in their supernatant samples (Type N1), PA expression mainly seen in supernatant samples (Type N2), and only low expression of PA in the samples of whole bacterial cells (Type W). The underlying reasons for the defects were mutations in the gene encoding PA as well as in the transcriptional processing of this gene for Type N1, defects in the sortase gene for Type N2, and low mRNA expression of PA for Type W. Since cellular hydrophobicity and phagocytosis susceptibility of the PA-defective isolates were significantly lower than those of the normal expression isolates, the potential implication of such defective isolates in systemic diseases involving bacteremia other than dental caries was suggested. Additionally, multilocus sequence typing was utilized to characterize S. mutans clones that represented a proportion of isolates with PA defects of 65-100%. Therefore, we described the molecular basis for variation defects in PA expression of S. mutans. Furthermore, we also emphasized the strong association between PA expression defects and serotypes f and k as well as the clonal relationships among these isolates. (C) 2015 Elsevier GmbH. All rights reserved.

DOI： 10.1016/j.ijmm.2015.03.001

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

Streptococcus mutans, a pathogen responsible for dental caries, is occasionally isolated from the blood of patients with bacteremia and infective endocarditis (IE). Our previous study demonstrated that serotype k-specific bacterial DNA is frequently detected in S. mutans-positive heart valve specimens extirpated from IE patients. However, the reason for this frequent detection remains unknown. In the present study, we analyzed the virulence of IE from S. mutans strains, focusing on the characterization of serotype k strains, most of which are positive for the 120-kDa cell surface collagen-binding protein Cbm and negative for the 190-kDa protein antigen (PA) known as SpaP, P1, antigen I/II, and other designations. Fibrinogen-binding assays were performed with 85 clinical strains classified by Cbm and PA expression levels. The Cbm(+)/PA(-) group strains had significantly higher fibrinogen-binding rates than the other groups. Analysis of platelet aggregation revealed that SA31, a Cbm(+)/PA(-) strain, induced an increased level of aggregation in the presence of fibrinogen, while negligible aggregation was induced by the Cbm-defective isogenic mutant SA31CBD. A rat IE model with an artificial impairment of the aortic valve created using a catheter showed that extirpated heart valves in the SA31 group displayed a prominent vegetation mass not seen in those in the SA31CBD group. These findings could explain why Cbm(+)/PA(-) strains are highly virulent and are related to the development of IE, and the findings could also explain the frequent detection of serotype k DNA in S. mutans-positive heart valve clinical specimens.

DOI： 10.1128/IAI.02164-14

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Streptococcus mutans, a Gram-positive bacterium, is considered to be a major etiologic agent of human dental caries and reported to form biofilms known as dental plaque on tooth surfaces. This organism is also known to possess a large number of transport proteins in the cell membrane for export and import of molecules. Nitrogen is an essential nutrient for Grampositive bacteria, though alternative sources such as ammonium can also be utilized. In order to obtain nitrogen for macromolecular synthesis, nitrogen-containing compounds must be transported into the cell. However, the ammonium transporter in S. mutans remains to be characterized. The present study focused on characterizing the ammonium transporter gene of S. mutans and its operon, while related regulatory genes were also analyzed. The SMU. 1658 gene corresponding to nrgA in S. mutans is homologous to the ammonium transporter gene in Bacillus subtilis and SMU. 1657, located upstream of the nrgA gene and predicted to be glnB, is a member of the PII protein family. Using a nrgA-deficient mutant strain (NRGD), we examined bacterial growth in the presence of ammonium, calcium chloride, and manganese sulfate. Fluorescent efflux assays were also performed to reveal export molecules associated with the ammonium transporter. The growth rate of NRGD was lower, while its fluorescent intensity was much higher as compared to the parental strain. In addition, confocal laser scanning microscopy revealed that the structure of biofilms formed by NRGD was drastically different than that of the parental strain. Furthermore, transcriptional analysis showed that the nrgA gene was co-transcribed with the glnB gene. These results suggest that the nrgA gene in S. mutans is essential for export of molecules and biofilm formation.

DOI： 10.1371/journal.pone.0107569

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

Black tooth staining is an extrinsic discoloration found in both primary and permanent dentition, and seen as dark pigmented lines extending to the gingival margin or an incomplete coalescence of dark dots that rarely extend beyond the cervical third of the crown. An association between black tooth staining and Actinomyces bacterial strains has been reported, while black-pigmented bacteria associated with such staining are known to be harbored in the oral cavity. Prevotella intermedia and Prevotella nigrescens are black-pigmented bacteria known to be dependent on the heme portion of hemoglobin as an iron source required for their growth. Recently, developments in molecular biological techniques have enabled rapid and easy detection of periodontopathic bacterial species using bacterial DNA extracted from oral specimens, such as plaque and saliva. Here, we report a case of black pigmentary deposition identified on all teeth of a 2-year-old girl, as well as the results of analysis of the distribution of oral bacteria in saliva and plaque specimens obtained from the patient using a molecular biological technique. In addition, a literature search found a case of disease related to the oral bacteria detected in our patient. We concluded that the bacteria detected in this case may have a strong relationship with black pigmentation, although the route of bacterial infection and cause of staining remain to be elucidated.

DOI： 10.1016/j.pdj.2014.09.003

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We analyzed the distribution of 11 periodontitis-related bacterial species in dental plaque collected from 176 Japanese dogs divided into young (less than 2 years of age), middle-aged (2-7 years of age) and elderly (more than 8 years of age) groups using a polymerase chain reaction method. Clinical examination revealed that no dogs in the young group were affected by periodontitis, whereas the rates for gingivitis and periodontitis were high in the middle-aged and elderly groups. In addition, the total numbers of bacterial species in the middle-aged and elderly groups were significantly greater than in the young group. Our findings suggest that age is an important factor associated with the distribution of periodontitis-related bacteria and periodontal conditions in dogs. © 2013 The Japanese Society of Veterinary Science.

DOI： 10.1292/jvms.13-0041

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Objective: Presently, a large number of individuals consider their companion animals as family members and have close contact with them in daily life. The purpose of the present study was to analyze the distribution of periodontopathic bacterial species in oral specimens taken from dogs and their owners. Design: Dental plaque specimens were collected from 66 dogs and 81 members of 64 families who came to an animal clinic or dog training school in Okayama, Japan, in 2011. Bacterial DNA was extracted from each specimen and PCR analyses using primers specific for 11 periodontopathic species, Porphyromonas gingivalis, Porphyromonas gulae, Treponema denticola, Tannerella forsythia, Capnocytophaga ochracea, Capnocytophaga sputigena, Prevotella intermedia, Prevotella nigrescens, Aggregatibacter actinomycetemcomitans, Campylobacter rectus, and Eikenella corrodens were performed. Results: P. gulae (71.2%), T. forsythia (77.3%), and C. rectus (66.7%) were frequently found in the dogs, whereas the detection rates of those species in humans were less frequent at 16.0%, 30.9%, and 21.0%, respectively. P. gulae was identified in 13 human subjects and each of their dogs was also positive for the species. Furthermore, E. corrodens and T. denticola in specimens obtained from dogs were correlated with their presence in specimens from owners who had close contact with them. Conclusions: These results suggest that several periodontopathic species could be transmitted between humans and their companion dogs, though the distribution of periodontopathic species in both is generally different. © 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.archoralbio.2012.02.015

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Streptococcus mutans, a major pathogen of dental caries, is occasionally isolated from the blood of patients with infective endocarditis. Bacterial attachment of exposed collagen tissue in the impaired endothelium is an important step in the onset of infective endocarditis. In our previous studies, some S. mutans strains were shown to possess collagen-binding activities and most of them had an approximately 120-kDa cell-surface collagen-binding protein called Cnm. However, several strains without Cnm proteins show collagen-binding properties. In the present study, another collagen-binding protein, Cbm, was characterized and its coding gene cbm was sequenced in these strains. The amino acid alignment in the putative collagen-binding domain of Cbm was shown to have approximately 80% identity and 90% similarity to the comparable region of Cnm. Cbm-deficient isogenic mutant strains constructed by insertional inactivation of the cbm gene, lacked collagen-binding properties, which were recovered in the complemented mutant. Analyses of a large number of clinical isolates from Japan, Thailand and Finland revealed that cbm-positive strains were present in all of these countries and that cnm-positive and cbm-positive strains were detected in the oral cavity of approximately 10 and 2% of systemically healthy subjects, respectively. In addition, cnm-positive strains were predominantly identified in the serotype f group, whereas cbm-positive strains were frequently detected in serotype k. These results suggest that Cbm as well as Cnm are major cell surface proteins of S. mutans associated with binding to type I collagen and predominantly identified in serotype k strains. © 2012 John Wiley &amp
Sons A/S.

DOI： 10.1111/j.2041-1014.2012.00649.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC VET SCI  

Porphyromonas gulae, a gram-negative black-pigmented anaerobe, is a pathogen for periodontitis in dogs. An approximately 41-kDa fimbrial subunit protein (FimA) encoded by fimA is regarded as associated with periodontitis. In the present study, the fimA genes of 17 P. gulae strains were sequenced, and classified into two major types. The generation of phylogenetic trees based on the deduced amino acid sequence of FimA of P. gulae strains along with sequences from several strains of Porphyromonas gingivalis, a major cause of human periodontitis, revealed that the two types of FimA (types A and B) of P. gulae were similar to type I FimA and types II and III FimA of P. gingivalis, respectively. A PCR system for classification was established based on differences in the nucleotide sequences of the fimA genes. Analysis of 115 P. gulae-positive oral swab specimens from dogs revealed that 42.6%, 22.6%, and 26.1% of them contained type A, type B, and both type A and B fimA genes, respectively. Experiments with a mouse abscess model demonstrated that the strains with type B fimA caused significantly greater systemic inflammation than those with type A. These results suggest that the FimA proteins of P. gulae are diverse with two major types and that strains with type B fimA could be more virulent.

DOI： 10.1292/jvms.11-0564

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

OBJECTIVE: Cervical or furcal root perforation is a serious clinical problem and one of its treatment modalities is perforation repair with composite resin. However, many cases still progress in inevitable extraction. When primary teeth are affected, early tooth loss can cause problems related to the eruption space for the permanent successors. The aim of the present study was to evaluate a novel clinical treatment method for perforated teeth. STUDY DESIGN: Atelocollagen was applied to perforated furcal and cervical areas of 13 primary teeth in 13 children aged 4-9 years and 8 permanent teeth in 8 adults aged 35-69 years after debridement with an electric knife. Thereafter the final restorations were performed after confirming good tooth conditions. Clinical evaluations were performed at follow-up examinations at approximately 3-month intervals. RESULTS: None of the treated primary teeth showed any clinical problems throughout the observation period, with eruption of the permanent successors noted in 7 cases. In the permanent teeth, no clinical problems were identified in any of the cases during follow-up periods of 10-60 months. CONCLUSION: This novel method may enable preservation of perforated primary teeth for a longer duration.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Pediatric Dentistry  

A 10Y2M-old girl was referred to our clinic by a general practitioner for consultation regarding an impacted supernumerary tooth identified in the maxillary left incisor region. Our intraoral examination revealed a maxillary left lateral incisor with a tubercle morphology, with slight swelling identified in the labial gingival area between the lateral incisor and primary canine. The dental age of the patient was calculated to be 1 year behind her chronological age based on root formation observed in orthopantomographs. X-ray photographic examinations revealed an impacted tooth on the labial side, with the root apex presumably directed into the palatal side. Computed tomography (CT) was used to produce three-dimensional reconstruction images in order to obtain morphological information for the impacted tooth, which had a tuberculate shape and an appearance that differed from that of the tooth on the opposite side, which showed a typical morphology of a lateral incisor. Periodical examinations were performed thereafter, which confirmed the developmental progress of the root formation of the impacted tooth. At 11Y8M, the tooth had emerged into the oral cavity and was extracted under local anesthesia. Based on this case, we concluded that effective use of CT is beneficial for consideration of treatment modalities in patients with an impacted tooth.

DOI： 10.11411/pdj.20.189

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Pediatric Dentistry  

Intracoronal resorption in an unerupted developing tooth is rare and most lesions of this type are incidentally found in radiographs taken for other purposes. A 5Y10M-old girl was referred to our clinic by a general practitioner for detailed examination of radiolucency identified in the unerupted mandibular left first permanent molar. Intraoral examination revealed that the affected tooth was unerupted, while the radiographic findings demonstrated a wide radiolucent area in the coronal part of the affected molar, which extended close to the pulp. There were no signs or symptoms associated with the tooth at the first examination. At 6Y4M of age, the affected tooth had emerged into the oral cavity, though the patient reported no symptoms. We performed surgical removal of the gingival tissue corresponding to the occlusal surface of the tooth under infiltration anesthesia and macroscopic appearance showed the affected tooth to be intact. However, when the enamel of the affected tooth was removed, a hollow portion approximately 2 mm into the tooth with no pulp exposure was revealed. Calcium hydroxide was applied to the bottom of the cavity and restoration with cement was performed. Three months after treatment, the patient had no abnormal signs or symptoms. A literature search found 15 similar cases, in which mandibular dentition was more frequently affected than maxillary dentition. As for treatment modalities in those cases, conservative restoration was preferably selected, though extraction was inevitable in approximately half.

DOI： 10.11411/pdj.20.207

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Objective: Streptococcus mutans is a major pathogen of dental caries and occasionally isolated from the blood of patients with infective endocarditis, though the association of its cell-surface glucosyltransferases (GTFB, GTFC, and GTFD) with pathogenicity for infective endocarditis remains to be elucidated. In this study, we investigated the contribution of S. mutans GTFs to platelet aggregation and analysed GTF expression profiles in a large number of clinical oral isolates.
Design: The platelet aggregation properties of GTF-defective isogenic mutant strains constructed from S. mutans reference strain MT8148 were evaluated using whole blood and platelet-rich plasma (PRP) taken from mice, as well as human PRP. In addition, GTF expression profiles for 396 S. mutans strains isolated from the oral cavities of 396 subjects were analysed by western blotting using antisera specific for each GTF.
Results: The platelet aggregation activities of the GTF-defective isogenic mutants were significantly lower than that of MT8148 when added to a large number of cells. Western blotting revealed no strains without GTF expression, though six strains had alterations of GTFB and GTFC as compared to MT8148. PGR analyses indicated that the gtf3-gtfC region length was approximately 4.5 kb shorter in those strains as compared to MT8148. These were designated as "GTFBC-fusion" strains and they demonstrated lower levels of platelet aggregation.
Conclusions: Our findings indicate that GTFs are associated with platelet aggregation. Although the clinical detection frequency of S. mutans strains with altered expressions is extremely low, GTFBC-fusion strains have activities similar to GTF-defective mutant strains. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.archoralbio.2010.03.017

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

DOI： 10.11411/pdj.20.99

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Objective: Streptococcus mutans, known to be a major pathogen of dental caries, is also considered to cause infective endocarditis. its 120-kDa Cnm protein binds to type I collagen, which may be a potential virulence factor. In this study, we characterized S. mutans clinical strains focusing on the cnm gene encoding Cnm.
Design: A total of 528 S. mutans strains isolated from Japanese, Finnish, and Thai subjects were investigated. Using molecular techniques, the distribution frequency of cnm-positive strains and location of the inserted cnm were analyzed. Furthermore, isogenic mutant strains were constructed by inactivation of the cnm gene, then their biological properties of collagen-binding and glucan-binding were evaluated. Southern hybridization of the genes encoding glucan-binding proteins was also performed.
Results: The distribution frequency of cnm-positive strains from Thai subjects was 12%, similar to that previously reported for Japanese and Finnish subjects. Furthermore, the location of insertion of cnm was the same in all cnm-positive clinical isolates. As for the cnm-inactivated mutant strains constructed from 28 clinical isolates, their collagen-binding activity was negligible. in addition, glucan-binding activity in the crim-positive clinical isolates was significantly reduced and corresponded to a lack of gbpA encoding glucan-binding protein A.
Conclusions: Our results indicate that strains with cnm genes, the most crucial factor for the collagen-binding property of S. mutans, are detectable at similar frequencies over several different geographic locations. In addition, the common properties of these strains are a high level of collagen-binding activity and tendency for a low level of glucan-binding activity. (C) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.archoralbio.2009.11.008

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2009&ichushi_jid=J00647&link_issn=&doc_id=20090424340229&doc_link_id=%2Fdu8shoni%2F2009%2F004702%2F234%2F0415-0415%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdu8shoni%2F2009%2F004702%2F234%2F0415-0415%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

DOI： 10.11411/pdj.19.123

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DOI： 10.11411/pdj.19.130

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DOI： 10.11411/pdj.19.117

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

DOI： 10.1016/s0917-2394(09)70167-3

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

DOI： 10.1111/j.1399-302X.2007.00421.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

Bacteria utilize quorum-sensing systems to modulate environmental stress responses. The quorum-sensing system of Streptococcus mutans is mediated by the competence-stimulating peptide (CSP), whose precursor is encoded by the comC gene. A comC mutant of strain GS5 exhibited enhanced antimicrobial sensitivity to a wide variety of different agents. Since the addition of exogenous CSP did not complement this phenotype, it was determined that the increased tetracycline, penicillin, and triclosan sensitivities resulted from repression of the putative bacteriocin immunity protein gene, bip, which is located immediately upstream from comC. We further demonstrated that the inactivation of bip or smbG, another bacteriocin immunity protein gene present within the smb operon in S. mutans GS5, affected sensitivity to a variety of antimicrobial agents. Furthermore, both the bip and smbG genes were upregulated in the presence of low concentrations of antibiotics and were induced during biofilm formation relative to in planktonic cells. These results suggest, for the first time, that the antimicrobial sensitivity of a bacterium can be modulated by some of the putative bacteriocin immunity proteins expressed by the organism. The implications of these observations for the evolution of bacteriocin immunity protein genes as well as for potential new chemotherapeutic strategies are discussed.

DOI： 10.1128/JB.00908-06

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

Probiotic bacteria such as lactobacilli and bifidobacteria are considered to be non-pathogenic and non-toxigenic on the basis of long years of safe usage. However, some species of lactobacilli are thought to be associated with the development of dental caries. The purpose of the present study was to examine the cariogenicity of the probiotic bacterium Lactobacillus salivarius in rats. Rats were divided into six groups, and infected with L. salivarius LS1952R and/or Streptococcus mutans MT8148R. L. salivarius LS1952R became established in the oral cavity of rats and induced significant level of dental caries even when infected for only 5 days from 18 to 22 days of age. In addition, the caries scores of rats superinfected with both Streptococcus mutans MT8148R and L. salivarius LS1952R from 18 days of age were significantly higher than those infected with either L. salivarius LS1952R or S. mutans MT8148R alone. Since strain LS1952R can adhere to saliva-coated hydroxyapatites, it is concluded that L. salivarius strain LS1952R possesses an inherent cariogenic activity following adherence to the tooth surface. Copyright (C) 2005 S. Karger AG, Basel.

DOI： 10.1159/000088183

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

Cacao bean husk extract (CBH) has been shown to possess antibacterial and antiglucosyltransferase activities through its unsaturated fatty acids and epicatechin polymers, respectively. In the present study, the antiplaque activities of CBH were examined in vitro and in vivo. The extract inhibited the adherence of Streptococcus mutans MT8148 to saliva-coated hydroxyapatite and reduced the accumulation of artificial dental plaque by S. mutans MT8148 on orthodontic wire. The number of mutans streptococci in dental plaque was also significantly reduced when human dental plaque was exposed to CBH from 21 children at 37degreesC for 1 h. For the in vivo study, 28 volunteers aged 19-29 yr old rinsed their mouth with CBH, before and after each intake of food and before sleeping at night for 4 d without using other oral hygiene procedures. Plaque depositions and the numbers of mutans streptococci were reduced in the subjects, compared with rinsing with 1% ethanol alone. These results indicate that CBH possesses significant antiplaque activity in vitro and in vivo.

DOI： 10.1111/j.1600-0722.2004.00134.x

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Total pages：209   Language：Japanese Book type：Textbook, survey, introduction

Language：Japanese Book type：Scholarly book

Language：Japanese Book type：Textbook, survey, introduction

Total pages：219  

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

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(一社)日本保育保健協議会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

教育問題検討委員会では、全国29歯科大学・大学歯学部の小児歯科学の講義を担当する講座を対象に、平成30年度版歯科医師国家試験出題基準の小児歯科学分野における必修の基本事項、歯科医学総論および各論の大・中・小項目の内容に関してのアンケート調査を行った。調査の結果、現状の必修および歯科医学総論の出題基準には、少なからず問題のあることがわかった。歯科医学各論に関しては、必修や総論に比べ、より具体性の高い出題基準になっていることが窺われた。必修・歯科医学総論および各論において、各々の小項目の記載がない中項目(以下、中項目とする)および小項目が小児歯科学分野の国家試験出題基準に該当するかの問いに対しては、「該当する」との回答が50%未満の中項目あるいは小項目が50%以上を占める大項目が多数認められた。(著者抄録)

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公財)8020推進財団  

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Language：Japanese   Publisher：(公社)日本歯科医師会  

近年、小児期のう蝕は減少傾向にあるといわれているが、実際には二極化しており、重症う蝕に罹患している子どもはむしろ増加傾向にある。小児期のう蝕は誤った生活習慣に起因していることが多く、小児のみならず保護者への指導が非常に重要である。歯科関係者は、小児期に生じる様々なう蝕の成り立ちを理解し、個々の症例における背景を正確に把握して、適切な生活習慣の改善へと導くことが必要である。(著者抄録)

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Language：Japanese   Publisher：(株)デンタルダイヤモンド社  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：東京臨床出版(株)  

現在の日本人小児の乳歯と永久歯の萠出時期、萠出順序、第一大臼歯と中切歯の萠出パターンを明らかにするとともに、1988年に小児歯科学会が行った前回調査結果と比較することで、日本人の乳歯・永久歯の萠出に変化が生じているか否かについて検討した。前回調査に準じた方法で全国的調査が行われ、調査対象児は、歯の萠出時期に影響を及ぼし、歯種判定困難、萠出判定困難に関連する全身疾患を有するものを除外し、乳歯に関しては生後3ヵ月から47ヵ月(3歳11ヵ月)、永久歯に関しては4歳0ヵ月から18歳11ヵ月の健常な日本人小児39549人とした。乳歯の分析対象は0〜3歳(男児4404人、女児4320人)、永久歯の分析対象は4〜18歳(男子15308人、女子15517人)であった。最初に萠出する乳歯である下顎乳中切歯の萠出時期が男児は6.8ヵ月(前回調査では8.0ヵ月)、女児は7.5ヵ月(前回調査では9.0ヵ月)と有意に早くなっていた永久歯の平均萠出年齢に関しては、前回調査と比較すると、男子では上下顎の第一小臼歯、第二小臼歯、第一大臼歯で本調査結果の方が有意に遅かった。乳歯の萠出時期のばらつきに関しては、標準偏差を比較すると、男児では全ての歯種に、女児では上顎乳側切歯を除き全ての歯種に今回調査が前回調査より大きい値を示した。萠出時期の最小-最大月齢の幅は、下顎の第一乳臼歯と第二乳臼歯を除いて男児より女児の方が小さかった。日本人の乳歯の萠出は前回調査より個人差が拡大している傾向がうかがわれた。また、永久歯の萠出時期のばらつきも大きくなっている傾向が明らかとなった。

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：岡山歯学会  

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急性リンパ性白血病患児に対して行われる多剤併用化学療法ではシクロホスファミド製剤を使用されることが多い。シクロホスファミドが口腔領域に及ぼす影響についてはこれまで、成熟した齧歯類の切歯形成やマウス臼歯の歯根形成に対する影響を調べた報告は複数あるものの、鐘状期歯胚の発育に対する影響を調べた研究は少ない。我々はマウス下顎第一臼歯歯胚の器官培養を行い、鐘状期歯胚にシクロホスファミドを作用させ、歯胚の発育に与える影響について、歯胚を構成する細胞の分化と細胞が産生する関連因子に着目して検討を行った。その結果、歯胚形成期のシクロホスファミド投与は歯胚の形態異常や発育障害をもたらすことが明らかになった。また、エナメル芽細胞や象牙芽細胞の分化を抑制することで歯冠形成の異常に関与することが示唆された。

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

日本人永久歯の萠出時期、萠出順序および第一大臼歯と中切歯の萠出パターンを明らかにし、約30年前と比べて永久歯の萠出に変化があるか否かを検討する目的で、4歳0ヵ月から18歳11ヵ月の小児30,825人を調査し、以下の結果を得た。1.男子の萠出は、1が5歳6ヵ月-7歳0ヵ月、6が5歳10ヵ月-7歳6ヵ月、1が6歳6ヵ月-7歳10ヵ月、2が6歳3ヵ月-8歳3ヵ月、6が5歳11ヵ月-8歳7ヵ月、2が7歳6ヵ月-9歳2ヵ月、3が9歳2ヵ月-11歳3ヵ月、4が9歳1ヵ月-11歳7ヵ月、4が9歳5ヵ月-11歳6ヵ月、3が9歳10ヵ月-12歳1ヵ月、5が10歳4ヵ月-13歳0ヵ月、5が10歳3ヵ月-13歳2ヵ月、7が11歳3ヵ月-13歳10ヵ月、7が12歳1ヵ月-14歳5ヵ月の順であった。2.女子の萠出は、1が5歳5ヵ月-6歳7ヵ月、6が5歳6ヵ月-7歳0ヵ月、1が6歳3ヵ月-7歳7ヵ月、2が6歳3ヵ月-7歳8ヵ月、6が5歳10ヵ月-8歳4ヵ月、2が7歳2ヵ月-8歳8ヵ月、3が8歳8ヵ月-10歳5ヵ月、4が8歳11ヵ月-11歳0ヵ月、4が9歳1ヵ月-11歳1ヵ月、3が9歳2ヵ月-11歳4ヵ月、5が10歳1ヵ月-12歳11ヵ月、5が10歳2ヵ月-13歳1ヵ月、7が11歳2ヵ月-13歳10ヵ月、7が11歳9ヵ月-14歳3ヵ月の順であった。3.萠出順序は、男女ともに上顎が6≒1→2→4→3→5→7で、下顎が1→6→2→3→4→5→7であった。4.第一大臼歯と中切歯の萠出パターンは、男子では上顎がM型77.2%、I型22.8%で、下顎がM型29.2%、I型70.8%であった。女子では上顎がM型73.4%、I型26.6%で、下顎がM型36.7%、I型63.3%であった。5.萠出時期の性差は、すべての歯種で女子が早く萠出しており、上下顎1、2、3、4および6に有意差が認められた。6.約30年前に比べて、男子は上下顎4、5、6が、女子は3、上下顎の4、5、6、7の萠出時期が有意に遅くなっていた。(著者抄録)

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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日本人乳歯の萠出時期および萠出順序を明らかにし、乳歯の萠出に変化が生じているか否かを検討する目的で、全国的に3ヵ月から3歳11ヵ月の小児8,724名を調査し、以下の結果を得た。1.男児の乳歯萠出は、下顎乳中切歯が5ヵ月-9ヵ月、上顎乳中切歯が7ヵ月-11ヵ月、上顎乳側切歯が9ヵ月-1歳2ヵ月、下顎乳側切歯が9ヵ月-1歳3ヵ月、下顎第一乳臼歯が1歳1ヵ月-1歳6ヵ月、上顎第一乳臼歯が1歳1ヵ月-1歳7ヵ月、上顎乳犬歯が1歳2ヵ月-1歳8ヵ月、下顎乳犬歯が1歳2ヵ月-1歳9ヵ月、下顎第二乳臼歯が1歳11ヵ月-2歳7ヵ月、上顎第二乳臼歯が2歳0ヵ月-2歳11ヵ月の順だったが、上顎乳側切歯・下顎乳側切歯間と下顎第一乳臼歯、上顎第一乳臼歯、上顎乳犬歯および下顎乳犬歯の間には有意な差は認められなかった。2.女児の乳歯萠出は、下顎乳中切歯が6ヵ月-9ヵ月、上顎乳中切歯が7ヵ月-11ヵ月、上顎乳側切歯が9ヵ月-1歳1ヵ月、下顎乳側切歯が9ヵ月-1歳2ヵ月、上顎第一乳臼歯が1歳1ヵ月-1歳7ヵ月、下顎第一乳臼歯が1歳1ヵ月-1歳7ヵ月、上顎乳犬歯が1歳3ヵ月-1歳9ヵ月、下顎乳犬歯が1歳4ヵ月-1歳9ヵ月、下顎第二乳臼歯が1歳11ヵ月-2歳7ヵ月、上顎第二乳臼歯が2歳1ヵ月-2歳10ヵ月の順だったが、下顎乳中切歯、上顎乳中切歯間、上顎乳中切歯・上顎乳側切歯間、上顎乳側切歯・下顎乳側切歯間、下顎第一乳臼歯・上顎第一乳臼歯間、上顎乳犬歯・下顎乳犬歯間には有意な差は認められなかった。3.性差は大部分の歯で認めず、上顎乳犬歯と下顎乳犬歯の萠出時期にのみ有意な差を認め、いずれも男児が1ヵ月早く萠出していた。4.前回報告(1988年)に比べて、男児は上顎乳中切歯、下顎乳中切歯、下顎乳犬歯、下顎第一乳臼歯の、女児は下顎乳中切歯と下顎第一乳臼歯の、萠出時期が有意に早くなっていることを認めた。(著者抄録)

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小児の悪性腫瘍の代表的な疾患である白血病あるいは固形腫瘍である横紋筋肉腫や髄芽種のうち、重度でステージが高く重症な症例においては放射線治療や大量化学療法に続き、その後に生じる造血機能不全を補うために造血幹細胞移植を行うケースが多い。造血幹細胞移植の際には、化学療法、免疫抑制剤、放射線治療を行うために、好中球がほとんど存在しない状態となり、口腔内には口腔粘膜障害が発症するリスクが最も高い。口腔粘膜障害の症状としては、発赤、出血、口内炎、潰瘍、および口角炎などがみられ、重度なものでは開口障害を生じる。口腔粘膜障害の治療としては対症療法が主となるが、周術期において早期に歯科的介入を行うことにより、症状を軽減させることが可能である。そのため、患者および保護者に口腔ケアの重要性を理解してもらうことが重要である。口腔ケアとしては、ブラッシング、含嗽、および保湿が挙げられる。さらに口腔粘膜障害は一旦消失しても慢性的に口腔内粘膜に拘縮が生じ、刷掃困難や唾液の減少による口腔内乾燥等が生じることが多くみられ、重度齲蝕や歯周病の発症がみられることもある。そのため小児においては、周術期の口腔ケアのみならず、長期にわたるフォローアップが重要である。(著者抄録)

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茶はツバキ科の植物であるCamellia sinensisの新芽を加工して得られ、その製造過程における発酵の程度によって不発酵茶、半発酵茶および発酵茶に分類される。茶の主要な化学成分は、ポリフェノール、カフェイン、アミノ酸、ビタミンCであるが、発酵の程度でその量は変化する。茶における抗齲蝕作用は古くから知られているが、その効果は茶に含まれるフッ素に起因すると考えられていた。しかし、緑茶の抽出物からフッ素を除いた標品にも抗齲蝕作用があることから、茶の主要成分でもあるポリフェノールにもその効果があることが注目されるようになってきた。近年、半発酵茶であるウーロン茶には緑茶や紅茶には存在しない特有のポリフェノールが存在し、抗齲蝕作用が明らかとなった。この作用は、むし歯の主要な病原性細菌であるStreptococcus mutansの産生する酵素の活性阻害によるものであり、ほかの茶ポリフェノールと比較して顕著に高いものであった。(著者抄録)

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Porphyromonas gulae is a gram-negative black-pigmented anaerobe which is known to be a pathogen for periodontitis in dogs. Approximately 41 kDa filamentous appendages on the cell surface (FimA) encoded by the fimA gene are regarded as important factors associated with periodontitis. The fimA genotype was classified into two major types and strains in type B were shown to be more virulent than those in type A. In the present study, we characterized a strain with a novel fimA genotype and designated it as type C. The putative amino acid sequence was shown to be similar to the genotype IV fimA of Porphyromonas gingivalis, a major pathogen of human periodontitis. Analyses using an oral squamous cell carcinoma cell line derived from tongue primary lesions revealed that the type C strain inhibited proliferation and scratch closure more than genotype A and B strains. In addition, experiments using a mouse abscess model demonstrated that the type C strain could induce much higher systemic inflammation when compared with strains of the other genotypes. Furthermore, molecular analyses of oral swab specimens collected from dogs demonstrated that the detection frequencies of P. gulae and the genotype C in the periodontitis group were significantly higher than those in the periodontally healthy group. These results suggest that FimA of P. gulae is diverse with the virulence of genotype C strains the highest and that molecular identification of genotype C P. gulae could be a possible useful marker for identifying dogs at high risk of developing periodontitis. (C) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.vetmic.2012.07.026

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

女性小児歯科医は日本小児歯科学会会員の約40%を占めるにも関わらず、現役で活躍し続けることが難しい現実がある。したがって、女性小児歯科医が生涯にわたり安心して仕事を続け、能力を発揮していくことができるために学会としてどのようなサポートが必要かを模索する必要がある。そこで全女性歯科医師会員を対象として女性の私生活と仕事に関するアンケートを実施した。今回、対象として日本小児歯科学会に所属する女性小児歯科医1766名のうち、回答のあった724名(回答率41.0%)について検討した。その結果、女性歯科医は仕事の継続に対して意欲が高い回答が多かったが、現状は職場環境の整備は十分とは言い難く、それを家族の協力によって補っていることが推察された。学会主催の大会、講習会などへの参加のためには託児所の設置が必要と感じており、近郊地域での講習会の開催、在宅でのセミナー受講に関する要望が多く、専門医の申請および更新について高い関心が示された。今後、多様な人材が小児歯科医療に携わり活躍できるようなダイバーシティーマネージメントが重要である。そのためには育児、介護期などのライフステージに応じたニーズへの対応が期待される。今回のアンケートから得られた結果をもとに、女性小児歯科医へのサポートおよび基盤整備のためのシステム構築の検討が必要であると考えられた。(著者抄録)

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Language：Japanese   Publisher：岡山歯学会  

標記S.mutansはヒトう蝕の主要な病原細菌であり、口腔内バイオフィルム形成において重要な細菌である。BipおよびSmbGは抗生物質の膜輸送に強く関連するタンパク質である。RecAは耐酸性に関与している。また、RecAはバイオフィルム形成に重要な役割を果たすと考えられるgtf遺伝子の発現制御にも関与している可能性がある。これらのタンパク質はS.mutansのシグナル伝達システムにおいて非常に重要な役割を担っていると考えられる。

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Language：Japanese   Publisher：動物臨床医学会  

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Language：Japanese   Publisher：日本歯科衛生学会  

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Language：Japanese   Publisher：(公社)日本小児保健協会  

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Language：Japanese   Publisher：岡山歯学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本獣医学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：岡山歯学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese   Publisher：(公社)日本小児歯科学会  

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Language：Japanese  

DOI： 10.11411/jspd1963.34.3_630

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