記述言語：日本語   出版者・発行元：(NPO)日本歯科保存学会  

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記述言語：日本語   出版者・発行元：(NPO)日本歯周病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSES: Osteoporosis and osteopenia are multifactorial diseases characterized by low bone mineral density (BMD) and are susceptible to genetic and environmental risk factors. The macrophage erythroblast attacher (MAEA) was discovered as a protein to mediate the attachment of erythroid cells to macrophages and is essential for bone marrow hematopoiesis. MAEA is expressed in a wide range of cells and tissues including osteoblasts and osteoclasts. Recent studies have shown that a single nucleotide polymorphism (SNP) rs6815464 (C/G) in the MAEA gene increases the susceptibility of type 2 diabetes mellitus. However, the contribution of MAEA to bone metabolism remains unknown. Therefore, we performed this study to evaluate the association between MAEA polymorphism and low BMD. METHODS: In a cross-sectional study with postmenopausal Japanese women living in the Yokogoshi area, Niigata City, we evaluated whether rs6815464 was associated with low BMD. Blood samples were collected from 353 subjects (age 63.8 ± 5.4 years). The MAEA genotype was determined by TaqMan assay. BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine (L2-L4), hip and femoral neck. Low BMD was defined as a T-score <-1. RESULTS: The percentage of subjects with low BMD in the lumbar spine, total hip and femoral neck were 71%, 75% and 84% respectively. After adjusting age, BMI, HbA1c, smoking and alcohol consumption, the G-allele carriage was found to be associated with low BMD of total hip (odds ratio = 2.11, 95% CI: 1.14-3.91, P = 0.018), but not of the lumbar spine or femoral neck. CONCLUSION: The MAEA gene polymorphism rs6815464 was associated with low hip BMD in postmenopausal Japanese women.

DOI： 10.1016/j.gene.2019.03.027

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Macrophage erythroblast attacher (MAEA) is a membrane protein that regulates the development of mature macrophages by mediating attachment with erythroblasts. A polymorphism rs6815464 (C/G) in MAEA gene was reported to be associated with type II diabetes. Along with diabetes, osteoporosis shows an increased prevalence in postmenopausal females, and both diseases have been reported to be associated with periodontitis. Therefore, we explored the relevance of the MAEA polymorphism to periodontitis, bone mineral density (BMD) and haemoglobin A1c (HbA1c). DESIGN: This was a cross-sectional study with the final sample comprised of 344 postmenopausal Japanese females. Probing pocket depth (PPD) and clinical attachment level (CAL) were measured. Genotype was determined by TaqMan assay. Blood biochemical parameters and BMD of the lumbar spine were evaluated. RESULTS: No differences were found in age, body mass index, HbA1c, BMD, number of teeth, bone metabolism parameters between the genotypes. Mean CAL and percentage of sites with PPD or CAL ≥ 5 mm were higher in the G-allele carriers than in the non-carriers. Multiple logistic regression analyses revealed that G-allele carriage was associated with severe periodontitis (odds ratio = 3.73, 95% CI = 1.36-10.19). CONCLUSION: Our results suggested that the MAEA gene polymorphism was independently associated with severe periodontitis.

DOI： 10.1016/j.archoralbio.2019.04.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Most studies that have demonstrated an association between number of remaining teeth and cognitive impairment have treated teeth as a continuous variable, although the relationship is nonlinear. The aim of this cross-sectional study was to determine the critical number of remaining teeth in hospital outpatients at which the association with cognitive impairment becomes apparent. Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in Project in Sado for Total Health. In total, 2,530 adults were interviewed and had their teeth counted; 1,476 of these individuals also completed the Mini-Mental State Examination (MMSE) and underwent measurement of their serum high-sensitivity C-reactive protein (hsCRP) levels. Patients on dialysis and those with hsCRP ≥ 10 mg/L were excluded. The final study group consisted of 565 adults (290 men and 275 women) of mean age 69.8 (range 29-91) years. An MMSE score < 24 was considered to indicate cognitive impairment. The subjects were categorized according to whether they had an edentulous jaw or one to 10, 11-20, 21-27, or ≥28 remaining teeth. One hundred twenty-eight of the 565 study participants were diagnosed to have cognitive impairment. Multiple logistic regression analysis revealed associations of cognitive impairment with older age, ischemic heart disease, smoking, and alcohol consumption. After adjustment for covariates, having one to 10 remaining teeth was significantly associated with cognitive impairment. There is a significant association between having only one to 10 remaining teeth and cognitive impairment in hospital outpatients.

DOI： 10.1002/cre2.147

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Munksgaard  

Background and Objectives: Previous reports suggest that several serum biomarkers play roles in the pathogenesis, inflammatory response, and oxidative stress in periodontitis caused by bacterial infections, linking chronic periodontitis to atherosclerotic vascular disease (ASVD). The aim of this preliminary study was to investigate, in a Japanese cross-sectional community survey, potential serum biomarkers of periodontitis that are associated with ASVD and chronic periodontitis. Material and Methods: The study cohort included a total of 108 male subjects who underwent annual health examinations. Serum biomarkers (high-sensitivity C-reactive protein [hs-CRP], proprotein convertase subtilisin/kexin type 9 [PCSK9], interleukin-6, tumor necrosis factor-α, soluble CD14, myeloperoxidase, matrix metalloproteinase-3, adiponectin, total bilirubin [TBIL], and serum lipids) were analyzed to determine their association (if any) with periodontal parameters. Aortic stiffness was evaluated using the brachial-ankle aortic pulse wave velocity (PWV) index and the cardio-ankle vascular index (CAVI). Results: The concentrations of PCSK9 and hs-CRP were increased (P =.001 and.042, respectively), and the concentration of TBIL was decreased (P =.046), in subjects with periodontal disease (determined as a probing depth of ≥4 mm in at least one site) compared with periodontally healthy subjects. The ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol and the concentrations of triglycerides, remnant-like particles-cholesterol, and oxidized LDL were elevated in subjects with periodontal disease compared with periodontally healthy subjects (P =.038,.007,.002, and.049, respectively). Multivariate regression analyses indicated that the number of sites with a pocket depth of ≥4 mm was associated with the concentration of PCSK9 and inversely associated with the concentration of TBIL independently (standardized β =.243, P =.040
standardized β = −.443, P =.0002
respectively). Analysis of receiver operating characteristic curves of PCSK9 indicated moderate accuracy for predicting the presence of disease sites (probing depth ≥ 4 mm) (area under the curve = 0.740). No significance in the values of PWV and CAVI was observed between subjects with periodontal disease and periodontally healthy subjects. Conclusion: In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. Moreover, PCSK9 could be a candidate biomarker for diagnosing chronic periodontitis, and may also have potential to evaluate the risk for periodontitis to cause ASVD. Longitudinal studies of larger populations are necessary to confirm the exact association of periodontitis with increased serum PCSK9 and decreased TBIL.

DOI： 10.1111/jre.12533

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The interaction of periodontopathic bacteria with host immune system induces the production of inflammatory mediators which leads to alveolar bone loss (ABL), the essential feature of periodontitis. Concurrently, periodontal diseases cause the elevation of blood cytokine levels, the alteration of gut microbiota and the dissemination of enterobacteria to the liver. Owing to these mechanisms, periodontal disease might be a risk for liver dysfunction. Several epidemiological studies have reported associations between periodontal diseases and liver dysfunction, although the association between ABL and liver dysfunction has not been investigated. This cross-sectional study determined if elevated serum liver enzyme levels were associated with ABL in Japanese adults. Material and Methods: Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in the study. Participants over 40 years of age who underwent dental panoramic radiography and blood tests were included. Drinking and smoking habits were self-administered. After excluding patients with edentulous jaw, diagnosed liver diseases, and those on dialysis, data from 44 men and 66 women with a mean age of 73 years were analyzed. The average percentage of ABL for each participant was calculated for mesial and distal sites of all remaining teeth. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were determined. Univariate analyses were performed to select covariates to be put in multivariate analyses. The association between elevated serum liver enzyme levels and the highest quartile of ABL were assessed by multiple logistic regression analysis. Results: After adjusting for covariates, no significant association was found between elevated serum AST, ALT, or GGT levels as dependent variables and the highest quartile of ABL as an explanatory variable. Conclusions: There was no significant association between the elevation of serum liver enzyme levels and ABL in Japanese adults. Key words:Liver enzymes, dental panoramic radiography, alveolar bone loss, Japanese adults.

DOI： 10.4317/jced.54555

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: An interrelationship between rheumatoid arthritis (RA) and periodontitis has been suggested due to their common pathogenic mechanisms. Protein carbamylation and neutrophil extracellular traps (NETs) formation have been shown to be related to autoimmune conditions, including RA, but their association with periodontitis has not been elucidated. Therefore, we assessed whether or not circulating levels of carbamylated protein (CarP) and NETs are associated with periodontitis severity and influenced by periodontal treatment. METHODS: We conducted a retrospective case-control study that included 40 patients with RA and periodontitis, 30 patients with periodontitis, and 43 systemically and periodontally healthy controls to assess the circulating levels of CarP and NETs and rheumatologic and periodontal conditions. The same assessments were also performed in 22 patients with RA and periodontitis after 2 months of periodontal treatment, including oral hygiene instruction and full-mouth supragingival scaling. RESULTS: Patients with RA and periodontitis showed significantly higher serum levels of CarP and NETs than the control group (P = 0.04 and P < 0.001, respectively). The serum levels of CarP and NETs were significantly correlated positively with the mean values of probing depth (P = 0.01 and P = 0.007, respectively) and clinical attachment level (P = 0.007 and P = 0.001, respectively) in the 40 patients with RA and periodontitis. Multiple logistic regression analyses also revealed significantly positive associations between the serum levels of CarP and NETs and moderate to severe periodontitis (P = 0.03 and P = 0.001, respectively). Furthermore, periodontal treatment significantly decreased the serum levels of CarP and NETs in patients with RA and periodontitis (P = 0.03 and P = 0.02). CONCLUSION: The circulating levels of CarP and NETs are associated with periodontitis severity and influenced by periodontal treatment in patients with RA.

DOI： 10.1371/journal.pone.0192365

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記述言語：日本語   出版者・発行元：(NPO)日本歯周病学会  

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記述言語：日本語   出版者・発行元：(NPO)日本歯科保存学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

OBJECTIVES: The aim of this study was to examine the association between periodontal disease and renal function in elderly women with different genotypes. MATERIAL AND METHODS: A total of 332 postmenopausal never-smoking women were analysed. Poor renal function was defined as serum cystatin C > 0.91 mg/l. Periodontal disease markers such as periodontal inflamed surface area (PISA) were evaluated. Selected variables, including PISA quartile, body mass index (BMI), HbA1C and age in Arg allele carriers and non-carriers based on the beta-3 adrenergic receptor, or between Ala allele carriers and non-carriers based on peroxisome proliferator-activated receptor gamma, were analysed using multiple logistic regression analysis. RESULTS: The odds ratios of serum cystatin C level and PISA (fourth quartile) were significantly positive for both Arg (2.52; p = 0.035) and Ala allele non-carriers (2.36; p = 0.021). A significant association was also found between serum cystatin C level and BMI for both Arg (1.18; p = 0.001) and Ala allele non-carriers (1.12; p = 0.003). CONCLUSION: The results of this study suggest that periodontal inflammation might be associated with renal function. Furthermore, in both the Arg and Ala allele non-carriers, the associations between BMI and PISA for renal function became stronger.

DOI： 10.1111/jcpe.12708

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Several studies have reported inconsistent results regarding the association between the PPARγPro12Ala polymorphism and obesity. Obese individuals had higher C-reactive protein (CRP) levels compared with those of normal weight, and PPARγ activation could significantly reduce serum high-sensitive CRP level. We have previously suggested that the Pro12Ala polymorphism represents a susceptibility factor for periodontitis, which is a known risk factor for increased CRP level. OBJECTIVES: The aim was to investigate associations between PPARγ gene polymorphism, serum CRP level, BMI and/or periodontitis among post-menopausal Japanese women. MATERIALS AND METHODS: The final sample in this study comprised 359 post-menopausal Japanese women. Periodontal parameters, including PD, CAL and BOP, were measured per tooth. PPARγPro12Ala genotype was determined by PCR-RFLP. Hs-CRP value was measured by a latex nephelometry assay. RESULTS: No significant differences in age, BMI or periodontal parameters were found between the genotypes. The percentages of sites with PD ≥ 4 mm were significantly higher among the hsCRP ≥ 1 mg/l group than the hsCRP < 1 mg/l group (p = 0.003). Positive correlations were found between serum hsCRP levels and the percentages of sites with PD ≥ 4 mm (p = 0.043) in PPARγ Ala allele carriers, and BMI (p = 0.033) in non-carriers. After adjustment for model covariates, BMI was significantly associated with serum hsCRP level. CONCLUSION: The PPARγPro12Ala polymorphism was not independently associated with periodontitis, serum CRP level or BMI in post-menopausal Japanese women. However, serum hsCRP level correlated with periodontitis in Ala allele carriers, and with BMI in non-carriers.

DOI： 10.1111/ger.12110

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: It has been hypothesized that β-3 adrenergic receptor and peroxisome proliferator-activated receptor gamma (PPARγ) might have gene-environmental and gene-gene interactions in periodontal disease. The purpose of this study is to elucidate the interaction between β-3 adrenergic receptor and PPARγ gene polymorphism with periodontal disease. METHODS: Three hundred thirty-two postmenopausal females were enrolled, and their serum high-sensitivity C-reactive protein (hsCRP) and hemoglobin A1c (HbA1c) were examined. β-3 adrenergic receptor and PPARγ genotypes were then determined. An oral examination was performed. The number of remaining teeth was counted, and the probing depth (PD) and clinical attachment level (CAL) were measured. Prevalence-rate ratios (PRRs) were calculated by multiple Poisson regression analyses to evaluate the relationship among periodontal disease markers, such as the number of sites with CAL 4 to 5 or ≥6 mm or PD 4 to 5 or ≥6 mm, and β-3 adrenergic receptor polymorphisms, PPARγ polymorphisms, and the interaction term adjusted by age, hsCRP, and HbA1c, after converting the number of remaining teeth (n) to an offset variable. RESULTS: In the participants with body mass index (BMI) ≥25, PRRs of β-3 adrenergic receptor genotype (Trp/Arg and Arg/Arg) for periodontal disease markers were 0.13 to 0.70 (P <0.0001 to 0.74), those of PPARγ genotype (Pro/Pro) were 0.66 to 3.14 (P = 0.01 to 0.68), and those of the interaction term for the two genotypes were 1.69 to 12.61 (P <0.0001 to 0.33). However, in the participants with BMI <25, a constant tendency was not observed. CONCLUSION: The results confirmed a positive relationship between the interaction term for β-3 adrenergic receptor genotype and PPARγ genotype and various periodontal markers in obese elderly females.

DOI： 10.1902/jop.2015.140472

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Ltd  

Objective IL-6 plays critical roles in bone resorption and the pathogenesis of periodontitis in both inflammation and alveolar bone loss. A negative correlation was observed between periodontitis and truncal bone mineral density (BMD) in postmenopausal women. The C allele carriers of a genetic polymorphism IL-6-572G/C have higher levels of serum IL-6 compared to G allele carriers. We investigated the possible effect of IL-6-572G/C polymorphism on the relationship between low BMD and periodontitis in postmenopausal women. Subjects and methods A total of 300 postmenopausal Japanese women who lived in Yokogoshi area of Niigata City, Japan, participated in this study. Genomic DNA was extracted from peripheral blood. The IL-6-572G/C genotypes were determined by the restriction fragment length polymorphism method. Bone mineral density (BMD) of right femoral neck and serum bone metabolism markers were measured. Low BMD was defined to have the BMD &lt
80% of the mean for young adults. Periodontal parameters at two sites per tooth were measured. Results Serum osteocalcin levels were significantly lower in the IL-6-572G/G genotype (p = 0.025). In the -572G allele non-carriers, percentages of PPD ≥ 4 mm sites were significantly higher in low BMD group compared with the healthy control group (p = 0.021). Logistic regression analysis revealed low BMD to be associated with periodontitis (Odds ratio = 1.736, p = 0.027) after adjusted with IL-6-572G carriage, age, serum albumin level. Conclusions IL-6-572G/C polymorphism was not an independent risk factor of low BMD or periodontitis, but may affect the relationship between the two diseases in postmenopausal Japanese women.

DOI： 10.1016/j.archoralbio.2014.12.005

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記述言語：日本語   出版者・発行元：The Japanese Society of Conservative Dentistry  

目的 : 化学的プラークコントロール法としてグルコン酸クロルヘキシジン (CHG) 配合洗口液が効果的であるが, アレルギーなどの副作用が問題視されている. そこで今回, 塩酸クロルヘキシジン (CHH) と塩化セチルピリジニウム (CPC) を抗菌成分として配合した洗口液を開発し, 基本治療終了後の歯周炎患者が4週間使用した場合の口腔細菌に対する効果を評価した. <br> 材料と方法 : 新潟大学医歯学総合病院歯周病科を受診中で, 20歯以上を有し歯周基本治療後5mm以上の歯周ポケットを1～7部位有する歯周炎患者30名を対象とした. 新洗口液 (CHH+CPC群), CHG配合のコンクールF (CHG群), 抗菌成分を含まないコントロール洗口液 (コントロール群) を使用する3群にランダムに各10名を割付け, 二重盲検法で比較した. ベースラインおよび使用4週後に唾液・舌苔・歯肉縁上プラークを採取し, 総菌数, 総レンサ球菌数, <i>Porphyromonas gingivalis</i>および<i>Streptococcus mutans</i>の菌数を測定した. またterminal restriction fragment length polymorphism (T-RFLP) 法による解析を行った. <br> 成績 : いずれの洗口液でも有害事象は認められなかった. ベースライン (術前) と4週目を比較した結果, CHH+CPC群において唾液中総菌数と<i>S. mutans</i>数, 舌苔中総菌数, 縁上プラーク中総レンサ球菌数が有意に減少していた. CHG群においては, 縁上プラーク中総菌数の有意な減少が認められた. コントロール群では舌苔中総菌数および総レンサ球菌数が有意に減少していた. T-RFLP解析の結果, CHH+CPC群の唾液中において制限酵素<i>Msp I</i>切断断片から推定されるStreptococcus群, <i>Hha I</i>切断断片から推定されるStreptococcus・Eubacterium群, Parvimonas群およびPorphyromonas・Prevotella群が有意に減少していた. 縁上プラーク中の細菌については, <i>Hha I</i>切断断片から推定されるStreptococcus・Veillonella群がCHG群で有意に減少していた. その他に有意な変化は認められなかった. <br> 結論 : これらの結果より, CHH+CPC配合洗口液はより安全に使用でき, CHG配合洗口液と同程度以上の抗菌効果をもつことが示唆された.

DOI： 10.11471/shikahozon.57.219

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J-GLOBAL

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The purpose of this study was to elucidate whether the association between beta-3 adrenergic receptor polymorphism and periodontal disease is modified by body weight. MATERIAL AND METHODS: We enrolled 332 postmenopausal women and determined their HbA1C levels (%) and beta-3 adrenergic receptor (rs4994) genotypes. Periodontal parameters including clinical attachment level (CAL) were measured. After selecting subjects for each body mass index (BMI) level, the prevalence rate ratio (PRR) by multiple Poisson regression analysis was calculated to evaluate the relationship between periodontal disease and beta-3 adrenergic receptor polymorphism. The number of sites with CAL≥6 mm was used as a dependent variable, and beta-3 adrenergic receptor genotype [categorized as Arg non-carriers (reference) or Arg carriers], age (y) and HbA1C (%) were adopted as independent variables. We converted the number of probing sites (n) to an offset variable. RESULTS: The PRR of the beta-3 adrenergic receptor genotype for the number of sites of CAL≥6 mm showed a positive association in subjects with BMI≥25.0 and increased markedly with BMI. The PRR in subjects with BMI≥30 was 3.10 (p < 0.0001). CONCLUSION: This study indicates a positive association between periodontal disease and the beta-3 adrenergic receptor genotype in obese individuals.

DOI： 10.1111/jcpe.12235

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

OBJECTIVE: Biomarkers in gingival crevicular fluid (GCF) have been investigated; however, measurements were limited by the small sample volume available. The aim of this study was to determine the levels of 40 different cytokines and chemokines in GCF samples. DESIGN: Eleven patients with generalised chronic periodontitis participating in a supportive periodontal therapy programme with remaining probing pocket depths (PDs) of >5mm were enrolled. One healthy and two diseased sites were sampled in each subject. Forty biomarkers in GCF were examined using a multiplex bead immunoassay. Porphyromonas gingivalis from the diseased sites was quantified by real-time polymerase chain reaction. RESULTS: Twenty-six biomarkers were detected in the GCF samples using the multiplex bead immunoassay. The levels of nine biomarkers were significantly different between the diseased and healthy sites after adjustment with Bonferroni's correction. The level of 26 biomarkers in diseased sites was compared between bleeding on probing (BOP)-positive and BOP-negative sites. Interleukin (IL)-1β and interferon-inducible protein (IP)-10 levels were significantly higher in BOP-positive diseased sites than BOP-negative diseased sites after adjustment for multiple comparisons (IL-1β, p=0.0007, IP-10; p=0.0009). In addition, the levels of IL-1β in GCF were found to be strongly correlated with the P. gingivalis ratio (r=0.646, p=0.0012). CONCLUSION: IL-1β levels in GCF correlate with the PDs, BOP and the presence of P. gingivalis in subgingival plaque. Multiplex bead assays can be useful in GCF studies. These findings can help in identifying new diagnostic methods in the diagnosis of periodontal disease.

DOI： 10.1016/j.archoralbio.2012.11.012

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その他リンク： http://orcid.org/0000-0002-7019-1872

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: PPARg regulates bone metabolism and inflammation. Our previous study suggested PPARg Pro12Ala polymorphism to represent a susceptibility factor for periodontitis in pregnant Japanese women. Several recent papers have drawn attention to a possible link between low bone mineral density (BMD) and periodontitis in postmenopausal women. Since the pathogenesis for both involve bone remodeling, they might share common risk factors such as gene polymorphisms and vitamin D level. The present study investigated possible associations between the PPARgPro12Ala polymorphism, periodontitis, BMD and serum 25(OH)D in postmenopausal Japanese women. MATERIALS AND METHODS: PPARgPro12Ala genotypes of 359 women were determined by PCR-RFLP. BMD and periodontal parameters of each woman were measured. Serum 25(OH)D levels were determined by radioimmunoassay. RESULTS: PPARgPro12Ala polymorphism was not associated with periodontitis or BMD as an independent factor. Serum 25(OH)D was significantly higher in Ala allele carriers compared to non-carriers. Only in the Ala allele carriers, positive correlations were found between mean clinical attachment level and BMD, between BMD and 25(OH)D, and between percentage of sites with probing depth ≥4 mm and 25(OH)D. CONCLUSIONS: PPARgPro12Ala polymorphism was not independently associated with periodontitis or BMD. However, the polymorphism might be a modulator of the relationship between the two conditions in postmenopausal Japanese women.© 2012 John Wiley &amp
Sons A/S.

DOI： 10.1111/odi.12032

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記述言語：日本語   出版者・発行元：特定非営利活動法人 日本歯科保存学会  

目的:歯周炎に対しスケーリング・ルートプレーニングを含む動的治療を行った後に残存したポケットに歯周病原細菌または炎症の継続が認められる場合,さらなる進行のリスクが高い.セルフケアとして,ブラッシングに薬剤を含む歯磨剤を併用し殺菌・消炎を図ることは,歯周炎の進行抑制に効果的と考えられる.歯磨剤ジェルコートFは,0.05%塩酸クロルヘキシジン,β-グリチルレチン酸,フッ化ナトリウム,ポリリン酸ナトリウムを含有している.今回,歯周治療後の残存歯周ポケットに対するジェルコートFの効果を調べた.材料と方法:対象は20歯以上を有する男女で,慢性歯周炎に対しスケーリング・ルートプレーニングを含む動的治療終了後1カ月以上経過し,2歯以上に6〜7mmの残存ポケットを有する20名とした.無作為化二重盲検法にて2群に分け実験群はジェルコートFを,コントロール群は塩酸クロルヘキシジン,β-グリチルレチン酸を除いたコントロール剤を使用した.残存ポケットを有する1歯を歯肉溝滲出液(GCF),ほかの1歯を細菌検査対象とし,GCF中のAST, ALT,縁下プラーク中のPorphyromonas gingivalis, Prevotella intermedia, Tannerella forsythiaおよびTreponema denticolaを測定した.歯周病検査を行った1週後(0w)にGCFと縁下プラークを採取し,次いでポケット内に歯磨剤を注入した.患者は毎日歯磨剤を使用してブラッシングを行い,就寝前にリテーナーにて歯磨剤を10分間適用した.4週後,同様の検査を行い結果を解析した.成績:実験群,コントロール群とも有害事象は認められなかった.ベースラインにおいて年齢,男女比,ポケット深さ,細菌レベル,GCF成分の差はなかった.術前術後比較では,実験群のみ対象歯のPlaque Index (PlI)とGingival Index (GI)が減少した.それ以外に有意な変化はなかった.また,術前術後の変化量に群間差はなかった.年齢・性別の影響を調整した線形回帰分析では,GIのみジェルコートFの効果が認められた.結論:リテーナーとブラッシングを併用してジェルコートFを4週間使用した結果,歯周治療後の残存ポケットの歯周病原細菌レベルおよび歯肉溝滲出液成分に有意な変化は認められなかった.しかし,臨床所見における縁上プラークおよび歯肉の炎症を減少させる可能性が示唆された.

DOI： 10.11471/shikahozon.56.344

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

FcγRIIB contains a unique immunoreceptor tyrosine-based inhibition motif (ITIM) and functions as a negative feedback regulator of leucocyte activation and antibody production. We have previously reported FcγRIIB-nt645+25A/G gene polymorphism to be associated with prevalence and severity of periodontitis, FcγRIIB expression level on peripheral B lymphocytes and the serum IgG level against periodontopathic bacteria. Previous studies have reported maternal periodontal disease to be associated with an increased risk for preeclampsia. Therefore, FcγRIIB-nt645+25A/G gene polymorphism may be associated with preeclampsia by affecting immune response to periodontopathic bacteria in pregnant women. To elucidate whether FcγRIIB-nt645+25A/G gene polymorphism has associations with preeclampsia and/or periodontitis in pregnant Japanese women, a case-control study was carried out on women with preeclampsia (n=13) and without preeclampsia (n=106). Maternal periodontal parameters and bacterial data of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque were collected within 5days of delivery. FcγR genotypes of each woman were determined using the genomic DNA isolated from peripheral blood. Serum IgG levels specific for each bacteria were determined. There was a significant association between FcγRIIB-nt645+25A/G polymorphism and preeclampsia (P=0.013). The frequency of the FcγRIIB-nt645+25AA genotype was higher in the preeclampsia group compared with the nonpreeclampsia group (P=0.007). The DNA level of A. actinomycetemcomitans from subgingival plaque was shown to be higher in the preeclampsia group (P=0.017). In conclusion, maternal FcγRIIB-nt645+25A/G polymorphism and subgingival DNA level of A. actinomycetemcomitans were significantly associated with the prevalence of preeclampsia in a limited number of Japanese women independently with periodontal infection. Further investigations should be performed to confirm this association in a larger population and to determine the biological process of the association. © 2012 Blackwell Publishing Ltd.

DOI： 10.1111/j.1744-313X.2012.01124.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Many studies have reported an association between periodontal disease and preterm birth, although this remains controversial. Cytokines and antibodies produced to give resistance to infection can enter the bloodstream and cause preterm labor. We analyzed maternal genetic polymorphisms in various immunoregulatory genes that could affect both preterm birth and periodontitis. A total of 1099 women referred to the Department of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital were candidates for participation, 424 of whom refused, and 553 were excluded. The final number of subjects was 122 (51 with preterm birth, 71 with term birth). Genomic DNA was isolated from venous blood, and 22 polymorphisms were determined: IL-1A, IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, TNFA, TNFRI, TNFRII, FcγRIIA, FcγRIIB, FcγRIIIA, FcγRIIIB, and FcαR. Within five days of labor, periodontal parameters were evaluated, and bacteria from subgingival plaque were detected using real-time PCR. There was no difference in the prevalence and degree of periodontitis between term and preterm births. Chi-squared tests showed that an age <33 years and FcαR(+56)T/C alleles were associated with preterm birth. Multiple logistic regression analysis represented a model with significant fitness in which four variables were associated with preterm birth: maternal age, number of Aggregatibacter actinomycetemcomitans, IL-6(-572)G/C, and FcαR(+56)T/C. In conclusion, there was no association between preterm birth and periodontitis in this study. A. actinomycetemcomitans, IL-6, and FcαR were suggested to be associated with preterm birth. Multiple logistic regression models with both genetic and environmental factors would be useful for evaluating susceptibility to preterm birth.

DOI： 10.1016/j.jri.2012.01.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To determine whether periodontitis and three prominent members of the periodontal flora are associated with the development of preeclampsia (hypertension plus proteinuria) Materials and Methods: The samples were composed of 127 systemically healthy women. Within 5 days after labour, clinical periodontal parameters and Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque were evaluated. Maternal serum IgG antibody specific for each bacteria was determined by enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was used to control for confounders (maternal age, body mass index before pregnancy, parity, and smoking). RESULTS: Eighteen women were affected with preeclampsia. The number of A.actinomycetemcomitans was shown to be significantly associated with preeclampsia in the logistic regression model (odds ratio; 1.7, 95% confidence interval; 1.1–2.7). There were statistically significant differences between the preeclamptic and control groups in body mass index before pregnancy, pre-term birth and low birthweight (respectively, p = 0.014, p = 0.010 and p < 0.0001). We found no statistically significant association between preeclampsia and periodontal clinical parameters or the presence of periodontitis. CONCLUSION: In systemically healthy pregnant women, our findings suggested that the levels of maternal subgingival A. actinomycetemcomitans DNA were elevated in preeclamptic women.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Sugita N, Iwanaga R, Kobayashi T, Yoshie H. Association of the Fc RIIB-nt645+25A/G polymorphism with the expression level of the Fc RIIb receptor, the antibody response to Porphyromonas gingivalis and the severity of periodontitis. J Periodont Res 2012; 47: 105113. (C) 2011 John Wiley & Sons A/S

DOI： 10.1111/j.1600-0765.2011.01411.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Objective: Recently, numerous studies have investigated the association of preterm birth with periodontitis. FcγRIIb is a human low-affinity receptor for immunoglobulin G (IgG). We have previously demonstrated single nucleotide polymorphisms (SNPs) of FcγRIIb to be associated with periodontitis and the serum-specific IgG level against periodontopathic bacteria. In this study, we investigated whether FcγRIIB gene polymorphisms were associated with periodontitis and/or pregnancy outcome. Material and Methods: We assessed the periodontal conditions of 122 Japanese pregnant women within 5d of delivery, and polymorphisms in FcγRIIB and in other Fcγ receptors were detected from the genomic DNA. Using clinical and genomic data, we analyzed the relationship between periodontitis, preterm birth and Fcγ receptor polymorphisms. Results: A significant difference was observed in the distribution of FcγRIIB-nt645+25A/G (rs2125685) between preterm and term birth groups, with a higher prevalence of nt645+25AA in the preterm birth group (p=0.032). Additionally, the FcγRIIB-nt645+25GG carrier showed significantly higher results for the prevalence of periodontitis (p=0.048), mean pocket depth (p=0.021), mean clinical attachment level (p=0.010), percentage of sites with pocket depth ≥4mm (p=0.005) and percentage of sites with clinical attachment level ≥3mm (p=0.007) than the AA carrier. An association between preterm birth and periodontitis was not observed in this study. Conclusion: These findings suggest that FcγRIIB-nt645+25AA carriers are more likely to experience preterm birth than FcγRIIB-nt645+25AG and GG carriers. Also, women with FcγRIIB-nt645+25G exhibited a greater tendency to have periodontitis than those with nt645+25A. © 2011 John Wiley &amp
Sons A/S.

DOI： 10.1111/j.1600-0765.2010.01338.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Previous studies suggest that periodontitis is closely related to obesity and metabolic syndrome. Leptin, a pleiotrophic hormone produced by adipose tissue, has been reported to be related to periodontitis. This study investigates the effects of periodontal treatment on the serum levels of leptin and other cytokines in patients with chronic periodontitis (CP). METHODS: Serum samples were taken from 33 CP patients (22 non-smokers, 11 smokers) and 18 healthy subjects. The serum leptin, adiponectin, tumor necrosis factor-alpha, interleukin (IL)-6, and C-reactive protein (CRP) levels were measured before and after non-surgical periodontal treatment. RESULTS: Significant differences between healthy and CP patients were found in serum leptin, IL-6, and CRP levels (P = 0.0018, P = 0.0064, and P = 0.0095, respectively). The serum leptin level was associated with mean probing depth, mean clinical attachment level, mean alveolar bone loss, and body mass index. There were significant associations between serum leptin levels and IL-6 and CRP levels. After non-surgical periodontal treatment, serum leptin, IL-6, and CRP levels were significantly decreased (mean +/- SD before and after, P value, respectively: leptin, 8.02 +/- 5.5, 7.10 +/- 4.4, P = 0.015; IL-6, 1.73 +/- 1.02, 1.36 +/- 0.73, P = 0.048; and CRP, 802.0 +/- 1065, 491.2 +/- 479.3, P = 0.047). CONCLUSIONS: Periodontal treatment is effective in reducing serum leptin, IL-6, and CRP levels. The results suggest that leptin, IL-6, and CRP could be mediating factors that connect metabolic syndrome and periodontitis.

DOI： 10.1902/jop.2010.090741

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recent studies suggest an association between maternal periodontitis and preterm birth, although the association remains controversial. It was suggested that mechanisms such as a genetic predisposition for a hyperinflammatory response cause periodontitis and preterm births. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor and ligand-dependent transcription factor. PPARgamma inhibits the transcriptional activity of the genes that produce proinflammatory mediators and repress periodontitis. Recently, a common polymorphism, proline(PRO)-to-alanine(ALA) mutation at codon12 in exonB (Pro12Ala: rs 1801282) PPARgamma, was reported to reduce the ability to transactivate responsive promoters. In this study, we tested whether the PPARgammaPro12Ala polymorphism was associated with maternal periodontitis and/or preterm birth. METHODS: Genomic DNA was isolated from the venous blood of pregnant Japanese women (term birth: n = 72; preterm birth: n = 58). The PPARgammaPro12Ala genotype was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Within 5 days after labor, clinical periodontal parameters were evaluated, and periodontopathic bacteria from the subgingival plaque were detected by species-specific PCR. RESULTS: The mean clinical attachment level (P = 0.012), mean probing depth (P = 0.031), mean gingival index (P = 0.037), and percentages of sites with bleeding on probing (P = 0.041) in women with the PPARgammaPro12Ala genotype were significantly higher than in women with the PPARgammaPro12Pro genotype. However, there was no association between preterm birth and periodontitis. CONCLUSION: We suggest that the PPARgammaPro12Ala polymorphism may represent a genetic susceptibility factor for the clinical measurements of periodontitis in a limited number of pregnant Japanese women, but it probably cannot influence the relationship between periodontitis and preterm birth.

DOI： 10.1902/jop.2010.090669

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Porphyromonas gingivalis (Pg) is one of the most harmful periodontal pathogens and it has been reported that Pg is associated with preterm birth (PTB), intrauterine growth retardation (IUGR) and pregnancy-induced hypertension (PIH), discovered by animal experiments and clinical research. The relationship between adverse pregnancy outcomes and maternal antibody response to Pg is controversial. On the other hand, the serum C-reactive protein (CRP) has been recognised as a reliable serum marker of periodontal disease. AIMS: To determine the significance of antibody responses to Pg affecting pregnancy outcomes in the first trimester. METHODS: A case-control study was carried out on women with PTB (n = 58), IUGR (n = 91), PIH (n = 32) and without any complications (control, n = 98). The serum level of the CRP and IgG1 against 40-kDa outer membrane protein of Pg (anti-40-kDa OMP Pg-IgG1) in the first trimester was measured. RESULTS: The IUGR group, and PTB patients whose placentas were diagnosed as chorioamnionitis or whose vaginal flora included Lactobacilli, showed a lower level of anti-40-kDa OMP Pg-IgG1 than the control group. There was no difference in the serum CRP level between each case group and control group. CONCLUSIONS: These results suggest that a lack of humoral immunity against Pg in early pregnancy is associated with IUGR and some PTB.

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記述言語：日本語   出版者・発行元：特定非営利活動法人 日本歯周病学会  

DOI： 10.14833/amjsp.2009f.0.28.0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Human Fc gamma RIIB is one of the receptors for immunoglobulin G (IgG) and suppresses the activation of B lymphocytes through cross-linking with the B cell receptor via immune complexes. This function of Fc gamma RIIB is essential for the negative regulation of antibody production. Our previous study has demonstrated the gene polymorphism Fc gamma RIIB-I232T to be associated with periodontitis. The polymorphism Fc gamma RIIB-232T has been reported to inhibit B-cell antigen receptor signaling more effectively compared to Fc gamma RIIB-232I, while other groups concluded that Fc gamma RIIB-232T had no ability to inhibit activatory receptors. In this study, we examined whether Fc gamma RIIB-I232T polymorphism would change the IgG antibody response to the periodontopathic bacteria Porphyromonas gingivalis.
Forty-seven patients with periodontitis were genotyped with the direct sequencing of genome DNA. Serum IgG and specific IgG subclass levels for the sonicate of P. gingivalis and the recombinant 40 kDa outer membrane protein (OMP) were determined.
No significant difference in the total IgG level and IgG response to P. gingivalis sonicate were observed between sera from Fc gamma RIIB-232T carriers and non-carriers. The Fc gamma RIIB-232T carriers revealed a significantly lower IgG(2) response to P. gingivalis 40 kDa OMP compared to non-carriers (p = 0.04, Mann-Whitney U-test). Lower responses of Fc gamma RIIB-232T carriers were also observed in specific IgG and IgG(1) levels. The Fc gamma RIIB-232T carriers revealed a low level of IgG(2) response to P. gingivalis 40 kDa OMP, even with a high average probing pocket depth.
These results suggest that association of the Fc gamma RIIB-232T allele with periodontitis might be related to the lower levels of antibody response to P. gingivalis.

DOI： 10.1111/j.1600-0765.2007.01078.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ACAD PERIODONTOLOGY  

BACKGROUND: The pathobiology of rheumatoid arthritis (RA) is similar to that of periodontitis in that proinflammatory cytokines and immunoglobulin G Fc receptor (FcgammaR) play an important role. Functional polymorphisms of interleukin (IL)-1 and FcgammaR were shown to be associated with susceptibility to both diseases. Therefore, we evaluated whether the IL-1 and FcgammaR gene polymorphisms represent a common risk factor for RA and periodontitis. METHODS: The study population consisted of Japanese adults with RA (RA group; N = 100), periodontitis only (P group; N = 100), and healthy individuals with no systemic or oral disease (H group; N = 100). Clinical periodontal condition was defined by measurements of probing depth, clinical attachment level, and bleeding on probing. Genomic DNA was isolated from peripheral blood and analyzed for determination of IL-1 genotypes (IL-1A+4845, IL-1B+3954, and IL-1RN+2028) and FcgammaR genotypes (FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB) by allele-specific polymerase chain reactions. RESULTS: Among 100 patients with RA, 86% showed periodontal tissue destruction. However, the RA group exhibited milder levels of periodontal tissue destruction than the P group (P <0.01). There was a significant difference in the distribution of IL-1B+3954 C/T genotypes between the RA and P groups and between the RA and H groups (P = 0.03 for both comparisons), with enrichment of the T allele in the RA group (P = 0.04; odds ratio, 2.9 for both comparisons). The combination of IL-1A+4845 T and IL-1+3954 T alleles yielded a strong association with RA and periodontitis (RA versus P group: P = 0.00001; RA versus H group: P = 0.00001). CONCLUSIONS: These results failed to show that IL-1 and FcgammaR gene polymorphisms constitute a common risk factor for RA and periodontitis. However, it was suggested that the distributions of IL-1B+3954 genotypes and IL-1A+4845 and IL-1B+3954 haplotypes were unique to the patients with RA and periodontitis.

DOI： 10.1902/jop.2007.070136

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

The functional bi-allelic polymorphism of immunoglobulin G (IgG) Fc receptor (Fc gamma R) IIa influences the efficiency of human IgG2 binding. Our previous study showed that the high affinity Fc gamma RIIa genotype (-H/H131) was associated with periodontitis risk. As interleukin-1 (IL-1) is one of the major causes of periodontal tissue destruction, it is hypothesized that the Fc gamma RIIa-H/H131cross-linking could induce an increased IL-1 release by mononuclear cells. In this study, we evaluated the intracellular expressions of IL-1 beta in CD14 positive cells upon stimulation with human IgG2 by flow cytometry. Fc gamma RIIa-H/H131 subjects exhibited a higher percentage of IL-1 beta-producing cells than Fc gamma RIIa-R/H131 and -R/R131 subjects (P &lt; 0.05). These results support the concept that Fc gamma RIIa genotype may affect IL-1 beta production, possibly leading to interindividual differences in periodontitis risk.

DOI： 10.1111/j.1744-313X.2007.00701.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The pathobiology of systemic lupus erythematosus (SLE) is similar to that of periodontitis in that the immunoglobulin G Fc receptor (FcgammaR) and proinflammatory cytokines play an important role. Genetic variations of FcgammaR and interleukin (IL)-1 are associated with susceptibility to both diseases. Therefore, we evaluated whether the combination of FcgammaR or IL-1 polymorphic genes represents a common risk factor for SLE and periodontitis. METHODS: The study population consisted of Japanese adults with SLE and periodontitis (SLE+P group; n = 46), SLE only (SLE group; n = 25), periodontitis only (P group; n = 58), and healthy individuals with no systemic or oral disease (H group; n = 44). Clinical periodontal condition was evaluated by measurement of probing depth, clinical attachment level, and alveolar bone loss. Genomic DNA was isolated from peripheral blood and analyzed for determination of FcgammaR genotypes (FcgammaRIIA, FcgammaRIIB, FcgammaRIIIA, and FcgammaRIIIB) and IL-1 genotypes (IL-1A +4845 and IL-1B +3954) by allele-specific polymerase chain reactions or DNA sequencing. RESULTS: A significant overrepresentation of the R131 allele of stimulatory FcgammaRIIA and the 232T allele of inhibitory FcgammaRIIB was found in the SLE+P group compared to the H group (P = 0.01 and P = 0.0009, respectively). The combination of FcgammaRIIA-R131 and FcgammaRIIB-232T alleles yielded a strong association with SLE and periodontitis (SLE+P group versus P group: P = 0.01, odds ratio: 3.3; SLE+P group versus H group: P = 0.0009, odds ratio: 11.2). Furthermore, SLE patients with the combined FcgammaR risk alleles exhibited more severe periodontal tissue destruction compared to other SLE patients. The frequencies of IL-1 polymorphic alleles were too low to assess the association with SLE or periodontitis. CONCLUSION: The combination of stimulatory FcgammaRIIA and inhibitory FcgammaRIIB genotypes may increase susceptibility to SLE and periodontitis in the Japanese population.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We describe the cloning and characterization of Siglec-H, a novel murine CD33-related siglec-like molecule with 2 immunoglobulin domains. Unlike other CD33-related siglecs, Siglec-H lacks tyrosine-based signaling motifs in its cytoplasmic tail. Although Siglec-H has the typical structural features required for sialic acid binding, no evidence for carbohydrate recognition was obtained. Specific monoclonal and polyclonal antibodies (Abs) were raised to Siglec-H and used to define its cellular expression pattern and functional properties. By flow cytometry, Siglec-H was expressed specifically on plasmacytoid dendritic cell (pDC) precursors in bone marrow, spleen, blood, and lymph nodes. Staining of tissue sections showed that Siglec-H was also expressed in a subset of marginal zone macrophages in the spleen and in medullary macrophages in lymph nodes. Using bone marrow-derived pDC precursors that express Siglec-H, addition of Abs did not influence cytokine production, either in the presence or absence of synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG). In comparison, Siglec-H functioned as an endocytic receptor and mediated efficient internalization of anti-Siglec-H Abs. By immunizing mice with ovalbumin-conjugated anti-Siglec-H Ab in the presence of CpG, we demonstrate generation of antigen-specific CD8 T cells in vivo. Targeting Siglec-H may therefore be a useful way of delivering antigens to pDC precursors for cross-presentation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1902/jop.2005.76.2.250

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The purpose of the present study was to investigate the effect of smoking cessation on the peripheral neutrophil mRNA expression levels for inflammatory cytokines, chemokine, growth factor and matrix metalloproteinase (MMP). MATERIAL AND METHODS: Sixteen male smokers (aged 22-39 [25.3+/-4.0] years), with no clinical signs of periodontal and systemic diseases, were recruited. The experiment was performed before (baseline) and at 1, 4 and 8 weeks after smoking cessation. The status of smoking and smoking cessation was verified by exhaled carbon monoxide (CO) concentration and serum cotinine concentration. Neutrophils were isolated from each subjects' peripheral blood, then the cell was stimulated with N-formyl-methionyl-leucyl-phenylalanine (FMLP). The mRNA expression levels for interleukin (IL)-1 beta, IL-8, tumor necrosis factor (TNF)-alpha, vascular endothelial growth factor (VEGF) and MMP-8 were analyzed by semiquantitative reverse transcription-polymerase chain reactions. The same experiment was performed on 11 non-smoking controls (four female and seven male), aged 23-27 (24.4+/-1.2) years. RESULTS: Eleven of 16 smokers successfully completed smoking cessation for 8 weeks. At 1 day after smoking cessation, there was a statistically significantly lower CO concentration than at baseline (p<0.01). Also, cotinine concentration markedly decreased at the second measurement, which was taken at 1 week. All of the analyzed mRNA expression levels of neutrophils from smokers were statistically significantly lower than that in non-smokers (p<0.01: IL-1 beta, IL-8, VEGF; p<0.05: TNF-alpha, MMP-8). The MMP-8 mRNA levels were statistically significantly increased at 8 weeks after smoking cessation compared with the baseline (p<0.05). Although the other mRNA expression levels were also elevated gradually from the baseline, they did not reach the statistically significant levels at 8 weeks after smoking cessation. CONCLUSION: The results showed that the neutrophil transcript levels in smokers were generally lower than those in non-smokers, which could be related to an impairment of neutrophils by smoking effects. The significant increase of MMP-8 mRNA levels were associated with the effects of smoking cessation, while recovery of the other mRNA levels seemed to require a bit longer period beyond 8 weeks after smoking cessation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ACAD PERIODONTOLOGY  

BACKGROUND: Leukocyte Fc receptors for immunoglobulin G (FcgammaR) play a major role in the handling of immune complexes and pathogens in systemic lupus erythematosus (SLE) and periodontitis. Both diseases have been shown to be partly influenced by genetic components including FcgammaR genotype. The aim of this study was therefore to evaluate whether FcgammaR gene polymorphisms are associated with periodontitis risk in SLE patients. METHODS: The study subjects consisted of 42 SLE patients with periodontitis (SLE/P), 18 SLE patients without periodontitis (SLE/H), 42 healthy subjects with periodontitis (H/P), and 42 healthy subjects without periodontitis (H/H), who were all unrelated Japanese non-smokers. Genomic DNA was isolated from peripheral blood, and FcgammaR genotypes for 3 biallelic polymorphisms (FcgammaRIIa-R131/H131, FcgammaRIIIa-158V/158F, FcgammaRIIIb-NA1/NA2) were determined by allele-specific polymerase chain reactions. RESULTS: The SLE/P group was found to have more mild levels of periodontal destruction than the H/P group (P < 0.01). There was a significant difference in the distribution of FcgammaRIIa genotypes between SLE/P and H/H groups (P = 0.004). A significant overrepresentation of the FcgammaRIIa-R131 allele was found in the SLE/P group compared to the H/H group (SLE/P versus H/H: odds ratio [OR] 3.13, 95% confidence interval [CI] 1.46-6.77, P = 0.0013). Furthermore, the prevalence of periodontitis was found to be 70% in SLE patients. The FcgammaRIIa-R131 allele was also found to be overrepresented in the SLE/P group compared to the SLE/H group (SLE/P versus SLE/H: OR 3.40, 95% CI 1.18-10.25, P = 0.011). CONCLUSION: These results show the FcgammaRIIa-R131 allele to be associated with periodontitis risk in SLE patients.

DOI： 10.1902/jop.2003.74.3.378

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MUNKSGAARD INT PUBL LTD  

Differential gene expression was investigated in neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine using RNA fingerprinting by arbitrarily pruned polymerase chain reaction (RAP-PCR). The cells were isolated from 3 groups of subjects: patients with generalized aggressive periodontitis (Aggressive-P, n=6), generalized chronic periodontitis (Chronic-P, n=6) and healthy controls (H, n=8). Our results show that 37 genes were upregulated, while 27 genes were down-regulated in all Aggressive-P neutrophils by using RAP-PCR with 45 primer pairs. Reverse transcript ion-PCR analyses revealed that mRNA levels were significantly different (p &lt; 0.05) for heat shock transcription factor 4b (HSF4b) gene, Kruppel-like zinc finger transcription factor 9 (Zf9) and muskelin genes. HSF4b was greater in neutrophils from Aggressive-P compared to groups I-I and Chronic-P. Zf9 and muskelin genes were lower in Aggressive-P compared to the H groups, but no significant difference was noted compared to the Chronic-P group. The control genes. IL-1&lt;beta&gt; and VEGF genes. were expressed at a significantly higher level in Aggressive-P and Chronic-P than H (p &lt; 0.01, p &lt; 0.05). In conclusion, the RAP-PCR technique used in this study enabled us to identify 3 Aggressive-P related genes, which had not been reported previously. Neutrophil functions in Aggressive-P patients are suggested to be altered by regulatory factors of the immune system including HSF4b (transcription factor), Zf9 (activator of TGF-beta) and muskelin (cellular adhesion).

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Functional polymorphisms of immunoglobulin G (IgG) Fc receptors (FcγR) have been shown to be associated with generalized aggressive periodontitis (GAgP) or recurrence of chronic periodontitis (CP) in Japanese patients. The purpose of this study was to evaluate whether FcγR polymorphisms are also associated with severity of CP. METHODS: Fifty Japanese non-smoking patients with severe CP and 39 Japanese non-smoking patients with moderate CP were identified according to established clinical criteria, including measurements of probing depth (PD), clinical attachment level (CAL), and alveolar bone loss (BL). FcγR genotypes for 3 bi-allelic polymorphisms (FcγRIIa-R/H131, FcγRIIIa-158V/F, FcγRIIIb-NA1/NA2) were determined in these CP patients and 64 race-matched, non-smoking healthy controls by means of allele-specific polymerase chain reactions. RESULTS: There was a significant over-representation of FcγRIIIa-158V allele in severe CP patients compared to moderate CP patients (odds ratio 2.03, 95% confidence interval [CI] 1.03-4.01, χ 2 = 4.86, P = 0.028). In addition, we found a strong association between CP severity and FcγR composite genotype comprising FcγRIIIa-158V plus FcγRIIIb-NA2 (severe CP versus moderate CP: odds ratio 4.69, 95% CI 1.52-15.10, χ 2 = 9.35, P = 0.002; severe CP versus healthy controls: odds ratio 4.10, 95% CI 1.62-10.59, χ 2 = 11.13, P = 0.0009). Moreover, CP patients positive for the composite genotype exhibited more severe signs of periodontitis than composite genotype-negative individuals (positive versus negative; mean PD: 3.8 mm versus 3.2 mm, P = 0.005; mean CAL: 4.5 mm versus 3.7 mm, P = 0.005; mean % BL: 37.6% versus 29.9%, P = 0.008). CONCLUSION: Our results document the FcγRIIIa-158V allele and possibly FcγRIIIb-NA2 to be associated with severity of CP in Japanese patients. J Periodontol 2001;72:1324-1331.

DOI： 10.1902/jop.2001.72.10.1324

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Early-onset periodontitis (EOP) is considered to have a genetic basis which has not been clearly defined. Genetic polymorphisms of the vitamin D receptor (VDR-B-b) and the immunoglobulin-Fcγ receptor IIIb (FcγRIIIb-NA1-NA2) are associated with bone metabolism and infectious diseases, respectively. The purpose of this study was to investigate the associations of EOP with VDR and FcγRIIIb polymorphisms. Subjects were comprised of those with generalized EOP (G-EOP, n = 42), adult periodontitis (AP, n = 52), and healthy control (HC, n = 55). VDR and FcγRIIIb genotypes were determined by allele-specific polymerase chain-reactions. Our results indicated that frequencies of the VDR-B non-carrier and the FcγRIIIb-NA2 carrier were lower in the G-EOP compared with the AP and HC groups. Furthermore, we found a strong association between G-EOP and the VDR-FcγRIIIb composite genotype (G-EOP vs. AP - OR = 5.09, p = 0.009
G-EOP vs. HC - OR = 5.93, p = 0.004). In conclusion, no correlation was found between the VDR genotype and G-EOP. However, the VDR and FcγRIIIb genotype combination may be associated with susceptibility to G-EOP.

DOI： 10.1177/00220345010800120501

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Functional polymorphisms of immunoglobulin G (IgG) Fc receptors (FcγR) have been shown to be associated with generalized aggressive periodontitis (GAgP) or recurrence of chronic periodontitis (CP) in Japanese patients. The purpose of this study was to evaluate whether FcγR polymorphisms are also associated with severity of CP. Methods: Fifty Japanese non-smoking patients with severe CP and 39 Japanese non-smoking patients with moderate CP were identified according to established clinical criteria, including measurements of probing depth (PD), clinical attachment level (CAL), and alveolar bone loss (BL). FcγR genotypes for 3 bi-allelic polymorphisms (FcγRIIa-R/H131, FcγRIIIa-158V/F, FcγRIIIb-NA1/NA2) were determined in these CP patients and 64 race-matched, non-smoking healthy controls by means of allele-specific polymerase chain reactions. Results: There was a significant over-representation of FcγRIIIa-158V allele in severe CP patients compared to moderate CP patients (odds ratio 2.03, 95% confidence interval [CI] 1.03-4.01, X2 = 4.86, P = 0.028). In addition, we found a strong association between CP severity and FcγR composite genotype comprising FcγRIIIa-158V plus FcγRIIIb-NA2 (severe CP versus moderate CP: odds ratio 4.69, 95% CI 1.52-15.10, X2 = 9.35, P = 0.002
severe CP versus healthy controls: odds ratio 4.10, 95% CI 1.62-10.59, X2 = 11.13, P = 0.0009). Moreover, CP patients positive for the composite genotype exhibited more severe signs of periodontitis than composite genotype-negative individuals (positive versus negative
mean PD: 3.8 mm versus 3.2 mm, P = 0.005
mean CAL: 4.5 mm versus 3.7 mm, P = 0.005
mean % BL: 37.6% versus 29.9%, P = 0.008). Conclusion: Our results document the FcγRIIIa-158V allele and possibly FcγRIIIb-NA2 to be associated with severity of CP in Japanese patients.

DOI： 10.1902/jop.2001.72.10.1324

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Academy of Periodontology  

Background: Genetic polymorphisms of immunoglobulin G (IgG) Fc receptors (FcγR) were recently shown to be associated with recurrence rates of adult periodontitis (AP). The purpose of this study was to evaluate whether FcγR polymorphisms are also associated with generalized early-onset periodontitis (G-EOP) in Japanese patients. Methods: Thirty-eight Japanese patients with G-EOP and 83 Japanese patients with AP were identified according to established clinical criteria, including measurements of probing depth, clinical attachment level, and alveolar bone level. FcγR genotypes for 3 bi-allelic polymorphisms were determined in these G-EOP and AP patients and 104 race-matched healthy controls by means of allele-specific polymerase chain reactions. Results: There was a significant difference in the distribution of FcγRIIIb genotypes between G-EOP patients and healthy controls (P = 0.02). Additionally, a significant over-representation of FcγRIIIb-NA2 allele was observed in G-EOP patients as compared to AP patients and controls (P = 0.02, P= 0.009, respectively). Moreover, we found a strong association between G-EOP and the composite genotype comprising FcγRIIIb-NA2 and FcγRIIIa-158F (G-EOP versus controls: odds ratio 2.4, 95% CI 1.0-6.0, χ2 = 4.13, P = 0.04). Conclusions: This study indicates that the FcγRIIIb-NA2 allele and possibly FcγRIIIa-158F could be associated with susceptibility to G-EOP in Japanese patients.

DOI： 10.1902/jop.2000.71.9.1425

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2177/jsci.21.supplement_225

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MUNKSGAARD INT PUBL LTD  

Our previous studies showed that the expression of CD23 on polymorphonuclear leukocytes (PMNLs) in gingival crevicular fluid (GCF) from adult periodontitis (AP) patients was higher than in autologous peripheral blood (PB). Percentages of eosinophils in GCF PMNLs ranged between 6 and 14%. The purpose of the present studies was to increase understanding of the potential role of eosinophils and their products, including CD23, in periodontal disease. We analysed the eosinophil fraction in GCF and PB by flow cytometry using monoclonal antibodies to CD23b (BB10), eosinophil cationic protein (ECP) in stored and secretory forms (EG1 and EG2), and CD67 (80H3). Simultaneously, we measured IgE and soluble CD23 titer and GCF and serum by ELISA. Flow cytometric analysis of BB10, EG2 and 80H3 binding showed that GCF eosinophils from AP were activated. A large BB10(+) EG2(+) cellular fraction was detected in GCF from AP whereas it was very low in autologous serum (9.30+/-2.460 vs 0.16+/-0.10, p&lt;0.001). GCF from gingivitis patients exhibited no flow cytometric evidence for the presence of BB10(+) EG2(+) cells. BB10(+) EG1(+) cells, or inactivated eosinophils rated lower in GCF than in PB both in gingivitis and periodontitis patients (0.45+/-0.63 vs 1.83+/-0.96 and 0.15+/-0.30 vs 1.30+/-0.20, p&lt;0.05, respectively). IEE titer in AP patients reached 1208.1+/-421.2 IU/ml in GCF while only 49.1+/-50.4 in sera. Soluble CD23 in GCF reached 236.1+/-81.3 ng/ml in GCF and 5.6 +/- 1.8 ng/ml in sera. GCF of gingivitis patients, however, contained no detectable sCD23. Thus, GCF from AP patients displayed a high rate of activated eosinophils secreting ECP, while GCF of gingivitis patients did not. These results suggest that ECP-secreting activated eosinophils are relevant to the pathology of adult periodontitis.

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

歯周病原菌であるTreponema denticola, Bacteroides属らのペプチダーゼ活性を特異的かつ迅速(15分間)に測定可能な酵素活性測定キットSK-013を用いて歯周病検査薬としての臨床的特異性およびSK-013のカットオフ値について検索した。歯周炎,歯肉炎,う蝕,健常,歯周組織炎罹患歯の歯肉溝から採取したプラークを用いたSK-013活性を検索した結果,SK-013は歯周炎罹患歯に特異的な活性を示した。スピロヘータ数を基準にSK-013のカットオフ値を検討した結果,0.2Try U/mlが最も高い診断率を示した。さらに,段階的な標準色調を用いた肉眼判定を試みた結果,分光光度計で測定した値と高い一致率(Efficacy 93.3%)を得た。以上よりSK-013は,スピロヘータ数,歯周炎の有無を計測機器を用いなくても簡便にかつ迅速に行なえ,チェアーサイドでの有用性が高いことが示された。

DOI： 10.2329/perio.33.154

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その他リンク： http://search.jamas.or.jp/link/ui/1993025408

記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

本研究の目的は,歯周病原菌が特異的に産生するペプチダーゼ活性を迅速に測定できる検査薬SK-013 kitを用いて,歯周ポケット掻爬術の効果判定を行い,その有用性を評価することである。歯周炎患者64名のうち33名を歯周治療群(T群),31名を末治療群(NT群)に分け,1名につき1歯を被検歯として選択した。T群にはブラッシングによるプラークコントロール(初診時開始)および歯周ポケット掻爬術(プラークコントロール後4週目)を行いその効果を臨床診査並びにSK-013 kitによる酵素活性検査にて評価した(6,8,12週目)。NT群については,特に歯周治療は行わず初診時および12週目に臨床診査並びに酵素活性検査を行った。その結果,SK-013活性値は,プラークコントロールのみでは変化を示さなかったが,歯周ポケット掻爬術後,GI,PD,AL,BOPと共に著しく減少した。NT群のSK-013活性は,いずれの検査時においても有意な変化は認められなかった。これらの結果よりSK-013 kitによる酵素活性測定法は,歯周治療効果をモニタリングするのに非常に高い有用性があることが示された。

DOI： 10.2329/perio.33.164

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その他リンク： http://search.jamas.or.jp/link/ui/1993025542

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ten periodontally affected subjects and 10 healthy subjects were selected in order to examine the duration patterns of percussion sounds in all upper teeth, excluding the 8′s. Probing depth, loss of attachment, tooth mobility by ‘Periotest’, bone loss and percussion sound duration via occlusal sound analyser were recorded during the pretreatment period. The following results were obtained from the study: the normal duration of percussion sounds ranged from 4.40–5.33 ms
percussion sound values of periodontal patients were of longer duration than those of healthy subjects
a close correlation between duration and other individual parameters was found in all upper teeth, with the exception of molars. Copyright © 1990, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1365-2842.1990.tb01429.x

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記述言語：日本語   出版者・発行元：JAPANESE SOCIETY OF PERIODONTOLOGY  

歯周病原性が疑われている<I>Bacteroides</I>属, <I>Treponema denticola</I>等のペプチダーゼ活性を特異的かつ迅速に (15分間) 測定可能な酵素活性測定キットSK-013を用いてこの酵素活性と臨床所見, ポケット内細菌との関係を検索した。PD, GIなどの臨床診査指数および総菌数, Spirochete (S) 数, Motilerod (M) 数, M&S比と酵素活性は統計学的に有意に相関したがその相関係数はポケット内細菌との方が高い値を示した。また臨床担当医の総合的診断, Spirocheteの有無を基準としたSK-013のカットオフ値は0.2TryU/m<I>l</I>であり, その際の診断率はSensitivity: 92%, Efficacy: 96%と, 高い値を示した。これらのことからSK-013は, ポケット内細菌の多寡, Spirocheteの有無歯周炎の有無の診断を簡便にかつ迅速に行なえ, チェアーサイドでの有用性が高いことが示された。

DOI： 10.2329/perio.32.241

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記述言語：日本語   出版者・発行元：JAPANESE SOCIETY OF PERIODONTOLOGY  

本研究の目的は歯周初期治療の効果判定をより正確にかつ迅速に判定する方法としてSK-013kitによる酵素活性検査法が有用であるかどうかを評価することである。歯周炎罹患歯36歯に初期治療としてプラークコントロール (初診時), およびスケーリング, ルートプレーニング (4週目) を行い, その効果を臨床診査, 位相差顕微鏡による細菌検査, 並びにSK-013kitによる酵素活性検査を用いて評価した (6, 8, 12週目) 。プラークコントロー-ルでもスケーリングとルートプレーニングでも, いずれも細菌検査値, SK-013kit値は有意に減少したものの臨床所見で共通して有意に減少したのはProbingDepthのみであった。また, SK-013kit値と常時有意な相関が認められたのも細菌検査値のみであった。以上より初期治療効果を判定する際にSK-013kitによる酵素活性測定法は臨床的に非常に有用性の高い診断法であることが示された。

DOI： 10.2329/perio.32.249

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記述言語：日本語  

DOI： 10.11471/shikahozon.58.109

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記述言語：日本語  

J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟大学  

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その他リンク： http://search.jamas.or.jp/link/ui/2006106162

記述言語：日本語   出版者・発行元：新潟大学  

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その他リンク： http://search.jamas.or.jp/link/ui/2005108491

記述言語：英語   出版者・発行元：NATURE PUBLISHING GROUP  

Human type II low-affinity receptor for immunoglobulin G (FcgammaRII) constitutes a clustered gene family consisting of FcgammaRIIA, IIB and IIC genes. FcgammaRIIB is unique in its ability to transmit inhibitory signals in B cells via immunoreceptor tyrosine-based inhibitory motif (ITIM). B-cell activation and subsequent elevated production of IgG are the immunopathological features of inflammatory disease such as periodontitis. To determine whether an association with periodontitis susceptibility exists, genetic polymorphisms of FcgammaRIIB were examined in Japanese patients with aggressive periodontitis (AGP) and chronic periodontitis (CP), and in the race-matched healthy controls (HCs). A significant difference was observed in the distribution of FcgammaRIIB - 232I/T allele (exon 5) between the AGP and HC groups, with enrichment of the 232T in the AGP group (P = 0.006). In addition, the FcgammaRIIB- nt 646 - 184A/G allele (intron 4) distribution was significantly different between the CP and HC groups, with enrichment of the nt 646 - 184A in the CP group (P = 0.011). These results document the association of FcgRIIB gene polymorphisms with susceptibility to periodontitis in the Japanese.

DOI： 10.1038/sj.gene.6364021

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

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記述言語：英語   出版者・発行元：BLACKWELL MUNKSGAARD  

Variation screening for the immunoglobulin G Fc receptor IIB (FcgammaRIIB) gene was performed with the genomic DNA from 100 healthy Japanese subjects. We identified 3 non-synonymous and 2 synonymous substitutions and 2 single-nucleotide polymorphisms in an intron region. These substitutions were found to be located in the ligand-binding domain and the intron, which might alter the function of FcgammaRIIb.

DOI： 10.1034/j.1399-0039.2001.580509.x

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：英語   出版者・発行元：AMER SOC MICROBIOLOGY  

Porphyromonas gingivalis has been implicated as a causative pathogen in periodontitis. Immunotherapeutic approaches have recently been suggested to aid in the clearance of P, gingivalis from disease sites. Because antibody-Fe receptor (FeR) interactions play a role in the effector functions of polymorphonuclear neutrophils (PMN), we evaluated which FeR on PMN from gingival crevicular fluid (GCF) serves as an optimal target molecule for FcR-directed immunotherapy. GCF PMN and peripheral blood (PB) PMN from adult periodontitis patients were analyzed for their immunoglobulin G (IgG) and IgA FcR (Fc gammaR and Fc alphaR, respectively) expression and function by studying IgG- and IgA-mediated elimination of P. gingivalis. GCF PMN exhibited higher Fc alpha RI and Fc gamma RI levels and lower Fc gamma RIIa and Fc gamma RIIIb levels than PB PMN. Functional studies revealed that GCF PMN exhibited less of a capacity to phagocytose and kill IgG1-opsonized P. gingivalis than PB PMN. IgA1-mediated phagocytosis and killing capacity was, however, comparable between GCF PMN and PB PMN. In summary, these in vitro results document that Fc alpha RI represents a candidate target for FcR-directed immunotherapy for the clearance of P. gingivalis.

DOI： 10.1128/IAI.69.5.2935-2942.2001

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記述言語：英語   出版者・発行元：MUNKSGAARD INT PUBL LTD  

Immunoglobulin G Fc receptor mb (Fc gamma RIIIb) is constitutively expressed on neutrophils, and has three allelic forms: Fc gamma RIIIb-NA1, Fc gamma RIIIb-NA2, and Fc gamma RIIIb-SH. We identified two Japanese subjects in whom an A to G substitution at nt 221 changes asparagine (N) to serine (S) at amino acid position 45 in the Fc gamma RIIIb-NA2 gene. Fc gamma RIIIb-NA2-specific mono-clonal antibodies (GRM1 and PEN1) did not bind to mutant neutrophils, which lack an N-linked glycosylation site. Furthermore, IgG3-mediated neutrophil phagocytosis by mutant was slightly increased as compared to wildtype donors.

DOI： 10.1034/j.1399-0039.2001.057004363.x

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：英語   出版者・発行元：AMER ASSOC DENTAL RESEARCH  

Many elderly people show minimum periodontal tissue destruction, which might be partly due to genetic advantages in host immune response against periodontopathic bacteria. The human IgG Fc receptor IIIb on neutrophils bears a NA1-NA2 polymorphism. The Fc gamma RIIIb-NA1 displays a more efficient interaction with IgG1- and IgG3-opsonized bacteria, compared with the Fc gamma RIIIb-NA2. We investigated a 70-year-old Japanese population (n = 599) to determine whether the Fc gamma RIIIb polymorphism was associated with resistance to periodontitis. Among subjects with greater than or equal to 20 teeth present, periodontitis-resistant (n = 46) and periodontitis-susceptible groups (n = 73) were selected based on the percentage of sites with greater than or equal to 4 nim probing attachment loss in the entire dentition. The Fc gamma RIIIb-NA1 allotype was overrepresented in the periodontitis-resistant group, compared with the periodontitis-susceptible group (chi (2) = 4.89, p = 0.03, odds ratio = 1.87, 95% CI, 1.07 to 3.28). This suggests that Fc gamma RIIIb-NA1 may be associated with resistance to periodontitis.

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記述言語：英語   出版者・発行元：Blackwell Munksgaard  

Differential gene expression was investigated in neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine using RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR). The cells were isolated from 3 groups of subjects: patients with generalized aggressive periodontitis (Aggressive-P, n = 6), generalized chronic periodontitis (Chronic-P. n = 6) and healthy controls (H, n = 8). Our results show that 37 genes were upregulated, while 27 genes were down-regulated in all Aggressive-P neutrophils by using RAP-PCR with 45 primer pairs. Reverse transcription-PCR analyses revealed that mRNA levels were significantly different (p &lt
0.05) lor heat shock transcription factor 4b (HSF4b) gene, Kruppel-like zinc finger transcription factor 9 (Zf9) and muskelin genes. HSF4b was greater in neutrophils from Aggressive-P compared to groups H and Chronic-P. Zf9 and muskelin genes were lower in Aggressive-P compared to the H groups, but no significant difference was noted compared to the Chronic-P group. The control genes, IL-1β and VEGF genes, were expressed at a significantly higher level in Aggressive-P and Chronic-P than H (p &lt
0.01, p &lt
0.05). In conclusion, the RAP-PCR technique used in this study enabled us to identify 3 Aggressive-P related genes, which had not been reported previously. Neutrophil functions in Aggressive-P patients are suggested to be altered by regulatory factors of the immune system including HSF4b (transcription factor), Zf9 (activator of TGF-β) and muskelin (cellular adhesion).

DOI： 10.1034/j.1600-0765.2001.360607.x

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記述言語：英語   出版者・発行元：Blackwell Munksgaard  

Differential gene expression was examined in human neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis (P. gingivalis-LPS) using RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR). LPS from Escherichia coli (E. coli-LPS) was used as control. More than 200 differently expressed transcripts were found in 8 subjects showing differential regulation at the transcriptional level. Densitometric analyses revealed that 42-100 genes were upregulated, while 53-116 genes were downregulated by P. gingivalis-LPS compared with E. coli-LPS. The results of sequencing identification showed the presence of supervillin (SVIL) and vascular endothelial growth factor (VEGF) genes in the clones which were upregulated by P. gingivalis-LPS. Consequently, semiquantitative analyses proved that the level of mRNA for SVIL and VEGF were significantly higher in P. gingivalis-LPS-stimulated neutrophils than in other bacterial (E. coli, Actinobacillus actinomycetemcomitans, Prevotella intermedia) LPS- or synthetic lipid A-stimulated neutrophils. Our findings suggest that an elevated mRNA expression for SVIL could be associated with impaired function of neutrophils when stimulated by P. gingivalis-LPS. Further, the VEGF mRNA over-expression might be related to the pathogenesis of P. gingivalis-associated periodontitis. The RAP-PCR technique used in this study enabled us to identify a number of P. gingivalis-LPS regulated genes which hitherto have not been reported.

DOI： 10.1034/j.1600-0765.2001.360304.x

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：英語   出版者・発行元：AMER ACAD PERIODONTOLOGY  

BACKGROUND: Genetic polymorphisms of immunoglobulin G (IgG) Fc receptors (FcγR) were recently shown to be associated with recurrence rates of adult periodontitis (AP). The purpose of this study was to evaluate whether FcγR polymorphisms are also associated with generalized early-onset periodontitis (G-EOP) in Japanese patients. METHODS: Thirty-eight Japanese patients with G-EOP and 83 Japanese patients with AP were identified according to established clinical criteria, including measurements of probing depth, clinical attachment level, and alveolar bone level. FcγR genotypes for 3 bi-allelic polymorphisms were determined in these G-EOP and AP patients and 104 race-matched healthy controls by means of allele-specific polymerase chain reactions. RESULTS: There was a significant difference in the distribution of FcγRIIIb genotypes between G-EOP patients and healthy controls (P = 0.02). Additionally, a significant over-representation of FcγRIIIb-NA2 allele was observed in G-EOP patients as compared to AP patients and controls (P = 0.02, P = 0.009, respectively). Moreover, we found a strong association between GEOP and the composite genotype comprising FcγRIIIb-NA2 and FcγRIIIa-158F (G-EOP versus controls: odds ratio 2.4, 95% CI 1.0-6.0, X2 = 4.13, P = 0.04). CONCLUSIONS: This study indicates that the FcγRIIIb-NA2 allele and possibly FcγRIIIa-158F could be associated with susceptibility to G-EOP in Japanese patients. J Periodontol 2000;71:1425-1432.

DOI： 10.1902/jop.2000.71.9.1425

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

Leukocyte IgG receptors (Fc gamma R) are important immune-response modulating molecules. Fc gamma RIIIa is expressed on macrophages, NK-cells and gamma delta-T cells and exhibits a genetically determined, functional polymorphism at nucleotide 559. This allelic difference predicts either a phenylalanine (F158) or valine (V158) at amino acid 158 in the membrane-proximal extracellular domain, and has been shown to be associated with autoimmune and infectious diseases. Published methods to determine Fc gamma RIIIa genotypes are cumbersome. Therefore, we developed a novel, rapid and reliable PCR-based method to determine Fc gamma RIIIa genotypes. Comparison of genotyping results with direct Fc gamma RIIIa sequencing of 60 blood donors showed 100% accuracy of this new method. Since genotype frequencies of Fc gamma R polymorphisms depend strongly on race and ethnicity, we compared Fc gamma RIIIa genotype frequencies of 176 Caucasian Dutch and 104 Japanese blood donors. Interestingly, these frequencies were not significantly different (P&gt;0.1), in contrast to the Fc gamma RIIa and Fc gamma RIIIb genotype frequencies (P&lt;0.001). (C) 2000 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0022-1759(00)00240-4

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：英語   出版者・発行元：MUNKSGAARD INT PUBL LTD  

Polymorphonuclear neutrophils (PMNs) are essential in host defense against periodontopathic bacteria such as Porphyromonas gingivalis. The uptake of immunoglobulin G (IgG)-opsonized bacteria via IgG Fc receptors (Fc gamma R) on PMN constitutes a central defense mechanism in periodontium. Fc gamma RIIIb is the most abundantly expressed Fc gamma R on PMN and is functionally polymorphic. The Fc gamma RIIIb-NA1 and IIIb-NA2 allotypes interact differently with IgG1- and IgG3-opsonized particles. We recently showed recurrence rates of adult periodontitis (AP) to be higher in patients carrying at least 1 Fc gamma RIIIb-NA2 allele. In this study we evaluated the functional relevance of the Fc gamma RIIIb polymorphism to anti-P. gingivalis PMN effector functions. Our results showed Fc gamma RIIIb-NA2-carrying PMN from both patients with AP and healthy controls to be less efficient in phagocytosis and induction of oxidative burst upon interaction with IgG1- and IgG3-opsonized P. gingivalis. These functional differences between Fc gamma RIIIb-NA1 and IIIb-NA2 were observed in the presence of CD32-blocking antibody fragments, but not upon blocking CD16. Moreover, PMNs from AP patients exhibited increased Fc gamma RIIIb-allelic differences in IgG3-induced oxidative burst compared to control PMNs. These results support the concept that Fc gamma RIIIb heterogeneity may influence the clinical course of AP.

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：英語   出版者・発行元：BLACKWELL SCIENCE LTD  

The immunoglobulin receptor Fc gamma RIIIa (CD16) is distributed on natural killer (NK) cells, macrophages, and gamma delta T cells, and is polymorphic. Fc gamma RIIIa-158V has a higher affinity for both monomeric and immune complexed IgG1, IgG3, and IgG4 than IIIa-158F. We determined Fc gamma RIIIa-158V/F genotypes of Japanese patients with adult periodontitis. A significant over-representation of Fc gamma RIIIa-158F was found in patients with recurrence, compared with patients without recurrence, making Fc gamma RIIIA a candidate gene for recurrence risk of adult periodontitis.

DOI： 10.1046/j.1365-2249.1999.00984.x

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：英語   出版者・発行元：PLENUM PUBL CORP  

DNA binding activity of NF-kappa B and AP-1 were examined in neutrophils stimulated with LPS purified from P. gingivalis, a major pathogenic bacteria of periodontitis lesion. Porphyromonas gingivalis LPS enhanced the activity reaching a peak at a concentration of 500 ng/ml in the absence of serum. The NF-kappa B activation stimulated with 10 ng/ml of P. gingivalis LPS was suppressed approximately 44% by treatment of neutrophils with anti-CD14 antibody under the presence of serum. Increase in the steady-state IL-8 mRNA level was concomitantly observed by stimulation of neutrophils with 500 ng/ml of P. gingivalis LPS under the absence of serum. These results indicate that P. gingivalis LPS activates NF-kappa B and AP-1 in both serum-dependent and -independent manners, followed by increased IL-8 transcription in neutrophils, and suggested a role for P. gingivalis LPS in IL-8 synthesis by neutrophils in inflamed gingiva and GCF.

DOI： 10.1023/A:1022344031223

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

A previous study has demonstrated that complement receptors on the surface of polymerphonuclear leucocytes (neutrophils) in gingival crevicular fluid significantly increased compared with those in autologous peripheral blood obtained from periodontitis-affected subjects. The present study attempted to determine the mRNA levels of complement receptor types 1 and 3 (CR1, CR3) on neutrophils in gingival crevicular fluid using reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Gingival crevicular fluid samples were obtained from 11 adult periodontitis patients by gingival crevicular washing, and venipunctured peripheral blood was used as a control. RT-PCR analysis was performed using the primer sets for CR1, CR3 and beta-actin. Digoxigenin-labelled RNA probes were synthesized from RT-PCR products for in situ hybridization. Both CR1 and CR3 mRNA levels relative to beta-actin were significantly lower in crevicular fluid neutrophils than in peripheral blood neutrophils (crevicular fluid-CR1: 32.75+/-22.93%, peripheral blood-CR1: 65.30+/-43.25%, p &lt;0.005; crevicular fluid-CR3: 9.09+/-5.34%, peripheral blood-CR3: 30.14+/-18.80%, p &lt;0.005). In in situ hybridization, a greater majority of neutrophils showed positive CR1 and CR3 mRNA expression, while only a few neutrophils showed positive signals in gingival crevicular fluid. Data in the present study suggest that increased expression of complement receptors on the neutrophil cell surface appears to be unrelated to de novo synthesis. (C) 1997 Elsevier Science Ltd.

DOI： 10.1016/S0003-9969(96)00110-0

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC DENTAL RESEARCH  

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

DOI： 10.2329/perio.38.243

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その他リンク： http://search.jamas.or.jp/link/ui/1997071747

記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

DOI： 10.2329/perio.38.243

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その他リンク： http://search.jamas.or.jp/link/ui/1997071747

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記述言語：英語   出版者・発行元：MUNKSGAARD INT PUBL LTD  

Polymorphonuclear leukocytes (PMNLs) are the most numerous cell population among the cellular infiltrates in gingival crevicular fluid (GCF) and play important roles in the host-defensive system in the gingival crevices. We determined the percentage of neutrophils, eosinophils and basophils in total PMNLs by light microscopic observation using Randolph-methylene blue staining, then assessed flow cytometric differences in the expression of CR3, FcgammaIII, FcepsilonRII, LFA-1alpha, and LFA-1beta on PMNL in GCF and peripheral blood (PB) from 21 patients with adult periodontitis (AP) and 13 healthy donors. Percentages of basophils and eosinophils were higher in GCF than in PB. In both AP patients and healthy subjects, expression of CR3 and FcepsilonRII was higher while FcgammaRIII was lower in GCF than in PB. The statistical analysis showed that the expressions of FcgammaRIII and FcepsilonRII on GCF PMNLs were lower in AP patients than in healthy subjects. Expressions of LFA-1alpha and beta on GCF were similar to those on PB PMNLs. PB PMNLs stimulated in vitro with Porphyromonas gingivalis culture supernatant and fMLP displayed an expression pattern of CR3, FcgammaRIII and FcepsilonRII on GCF PMNLs. However, C5a and IL-1 failed to induce changes in FcgammaRIII and FcepsilonRII. The results indicate that GCF neutrophils are activated, present enhanced adhesion and a decreased IgG-binding ability which would reflect that they are at the terminal stage of activation, and that GCF contains a larger eosinophil-fraction than in PB. Moreover, these GCF eosinophils appear to be activated.

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：日本語   出版者・発行元：特定非営利活動法人日本歯周病学会  

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記述言語：日本語   出版者・発行元：日本顎口腔機能学会  

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