Autoimmunity to citrullinated type II collagen in rheumatoid arthritis

The production of autoantibodies to citrullinated type II collagen and the citrullination of type II collagen were analyzed in rheumatoid arthritis. Autoantibodies to citrullinated type II collagen were detected in 78.5% of serum samples from 130 rheumatoid arthritis patients. Autoantibodies to native noncitrullinated type II collagen were detected in 14.6% of serum samples, all of which were positive for anti-citrullinated type II collagen antibodies. Serum samples were also positive for anti-citrullinated type II collagen antibodies in 1 of 31 systemic lupus erythematosus patients and 2 of 55 patients with osteoarthritis of the knee. In contrast, sera samples from 24 systemic sclerosis patients, 21 dermatomyositis/polymyositis patients, 21 ankylosing spondylitis patients, and 18 psoriatic arthritis patients were all negative for anti-citrullinated type II collagen antibodies. Anti-citrullinated type II collagen antibodies and fragments of citrullinated type II collagen were found in the synovial fluid obtained from affected knee joints of 15 rheumatoid arthritis patients. Moreover, anti-citrullinated type II collagen antibodies were isolated from the synovium of affected knee joints in 8 rheumatoid arthritis patients using antigen/antibody immunocomplex dissociation buffer but not by using standard buffers. These findings indicate that autoantibodies that react with citrullinated type II collagen are specifically produced and that immunocomplexes composed of fragments of citrullinated type II collagen and autoantibodies are deposited in the inflamed articular synovium in rheumatoid arthritis patients. Assaying for the presence of anti-citrullinated type II collagen antibodies may therefore be useful for diagnosing rheumatoid arthritis, and the deposition of these immunocomplexes in the articular synovium may be involved in pathogenesis

Intrafamilial clustering of genotypes of hepatitis C virus RNA.

Hepatitis C virus (HCV)-RNA in the blood was measured by polymerase chain reaction (PCR) in 37 subjects from eight families in which 2 or more persons tested seropositive for antibodies against C100-3 or CP9. HCV-RNA was positive in 17 of 37 subjects. Two or more HCV-RNA-positive subjects were observed in six of the families. Intrafamilial HCV infection was studied by determining the HCV-RNA type (I, II, III or IV) by PCR using type-specific primers. In two families, all of the subjects showed type III infection, and in three other families, all of the subjects showed type II infection, with different types of HCV infections being observed in only one family. The HCV type was uniform in all but one. These findings suggest a possibility of intrafamilial infection between husbands and wives and between members of the same household.</p

Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis

Regenerative therapy to replace missing teeth is a critical area of research. Functional bioengineered teeth have been produced by the organ germ method using mouse tooth germ cells. However, these bioengineered teeth are significantly smaller in size and exhibit an abnormal crown shape when compared with natural teeth. The proper sizes and shapes of teeth contribute to their normal function. Therefore, a method is needed to control the morphology of bioengineered teeth. Here, we investigated whether insulin-like growth factor 1 (IGF1) can regulate the sizes and shapes of bioengineered teeth, and assessed underlying mechanisms of such regulation. IGF1 treatment significantly increased the size of bioengineered tooth germs, while preserving normal tooth histology. IGF1-treated bioengineered teeth, which were developed from bioengineered tooth germs in subrenal capsules and jawbones, showed increased sizes and cusp numbers. IGF1 increased the number of fibroblast growth factor (Fgf4)-expressing enamel knots in bioengineered tooth germs and enhanced the proliferation and differentiation of dental epithelial and mesenchymal cells. This study is the first to reveal that IGF1 increases the sizes and cusp numbers of bioengineered teeth via the induction of enamel knot formation, as well as the proliferation and differentiation of dental epithelial and mesenchymal cells

Hepatitis C virus antibody titration in patients with chronic hepatitis C, before and after interferon treatment.

We measured hepatitis C virus antibody titers in 13 patients with chronic hepatitis C to determine whether titration of hepatitis C virus antibody was useful or not, to predict and evaluate the efficacy of interferon (IFN) treatment. During administration of IFN, hepatitis C virus titers declined in all patients. Antibody titers performed before treatment as well as just at the end of treatment did not correlate with change of the alanine aminotransferase levels during administration of IFN. Antibody titers declined continuously after treatment in 5 patients with normal alanine amino-transferase levels for over 6 months after discontinuation of IFN. Antibody titers rose again in 6 patients whose alanine aminotransferase levels fluctuated after treatment. An exceptional pattern of change occurred in 2 patients whose antibody titers declined continuously although their alanine aminotransferase levels fluctuated after treatment. Repeated titration of hepatitis C virus antibody appears to be useful for evaluating the long-term efficacy of IFN treatment.</p

Association of dietary fiber intake with subsequent fasting glucose levels and indicators of adiposity in school-age Japanese children

Abstract Objective: To evaluate the relationships of fiber intake with subsequent body mass index SD-score, waist-to-height ratio, and serum fasting glucose levels among school-age Japanese children. Design: A prospective study of school-age Japanese children. Participants were followed from 6–7 to 9–10 years of age (follow-up rate: 92.0%). Fiber intake was assessed using a validated food frequency questionnaire. Serum fasting glucose was measured by a hexokinase enzymatic method. Using a general linear model, the associations between dietary fiber intake at baseline and body mass index SD-score, waist-to-height ratio, and serum levels of fasting glucose at follow-up were evaluated after considering potential confounding factors. Setting: Public elementary schools in a city in Japan Participants: A total of 2,784 students. Results: The estimated means for fasting glucose at 9–10 years of age were 86.45, 85.68, 85.88, and 85.58 mg/dl in the lowest, second, third, and highest quartile of fiber intake at 6–7 years of age, respectively (p= 0.033, trend p= 0.018). Higher fiber intake at 6–7 years of age was associated with lower waist-to-height ratio at 9–10 years of age (trend p= 0.023). The change in fiber intake was inversely associated with concurrent change of body mass index SD-score (trend p= 0.044). Conclusion: These results suggest that dietary fiber intake may be potentially effective to limit excess weight gain and lower glucose levels during childhood

Association between shift work and the risk of death from biliary tract cancer in Japanese men

Background: There is increasing evidence suggesting that shift work involving night work may increase cancer risk. Methods: We examined the association between working rotating shifts and the risk of death from biliary tract cancer among Japanese men who participated in the Japan Collaborative Cohort Study. Of the 46, 395 men recruited, 22, 224 men aged 40-65 at baseline (1988-1990) who reported working full-time or were self-employed were included in the present analysis. The study subjects were followed through December 31, 2009. Information regarding occupation and lifestyle factors was collected using a self-administered questionnaire. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for the risk of death from biliary tract cancer in relation to shift work. Results: During a mean 17-year follow-up, we observed 94 biliary tract cancer deaths, including 23 deaths from gallbladder cancer and 71 deaths from extrahepatic bile duct cancer. Overall, shift work was associated with a statistically non-significant increase in the risk of biliary tract cancer, with an HR of 1.50 (95 % CI: 0.81-2.77), among rotating shift workers. When the analysis was limited to extrahepatic bile duct cancer, a significant association appeared, with a multivariable-adjusted HR of 1.93 (95 % CI: 1.00-3.72) for rotating shift workers. Conclusion: Our data indicate that shift work may be associated with increased risk of death from extrahepatic bile duct cancer in this cohort of Japanese men. The association with gallbladder cancer remains unclear because of the small number of deaths

Seaweed intake and blood pressure levels in healthy pre-school Japanese children

<p>Abstract</p> <p>Background</p> <p>Few studies have examined whether dietary factors might affect blood pressure in children. We purposed to investigate whether seaweed intake is associated with blood pressure level among Japanese preschool children.</p> <p>Methods</p> <p>The design of the study was cross-sectional and it was conducted in autumn 2006. Subjects were healthy preschoolers aged 3-6 years in Aichi, Japan. Blood pressure and pulse were measured once by an automated sphygmomanometer, which uses oscillometric methods. Dietary data, including seaweed intake, were assessed using 3-day dietary records covering 2 consecutive weekdays and 1 weekend day. Of a total of 533 children, 459 (86.1 percent) agreed to be enrolled in our study. Finally, blood pressure measurement, complete dietary records and parent-reported height and weight were obtained for 223 boys and 194 girls.</p> <p>Results</p> <p>When we examined Spearman's correlation coefficients, seaweed intake was significantly negatively related to systolic blood pressure in girls (<it>P </it>= 0.008). In the one-way analysis of covariance for blood pressure and pulse after adjustments for age and BMI, the boys with the lowest, middle and highest tertiles of seaweed intake had diastolic blood pressure readings of 62.8, 59.3 and 59.6 mmHg, respectively (<it>P </it>= 0.11, trend <it>P </it>= 0.038). Girls with higher seaweed intake had significantly lower systolic blood pressure readings (102.4, 99.2 and 96.9 mmHg for girls with the lowest, middle and highest tertiles of seaweed intake, respectively; <it>P </it>= 0.037, trend <it>P </it>= 0.030).</p> <p>Conclusion</p> <p>Our study showed that seaweed intake was negatively related to diastolic blood pressure in boys and to systolic blood pressure in girls. This suggests that seaweed might have beneficial effects on blood pressure among children.</p

Thymic Alterations in GM2 Gangliosidoses Model Mice

BACKGROUND: Sandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of GM2 ganglioside and related glycolipids. We have previously found that the progressive neurologic disease induced in Hexb(-/-) mice, an animal model for Sandhoff disease, is associated with the production of pathogenic anti-glycolipid autoantibodies. METHODOLOGY/PRINCIPAL FINDINGS: In our current study, we report on the alterations in the thymus during the development of mild to severe progressive neurologic disease. The thymus from Hexb(-/-) mice of greater than 15 weeks of age showed a marked decrease in the percentage of immature CD4(+)/CD8(+) T cells and a significantly increased number of CD4(+)/CD8(-) T cells. During involution, the levels of both apoptotic thymic cells and IgG deposits to T cells were found to have increased, whilst swollen macrophages were prominently observed, particularly in the cortex. We employed cDNA microarray analysis to monitor gene expression during the involution process and found that genes associated with the immune responses were upregulated, particularly those expressed in macrophages. CXCL13 was one of these upregulated genes and is expressed specifically in the thymus. B1 cells were also found to have increased in the thy mus. It is significant that these alterations in the thymus were reduced in FcRγ additionally disrupted Hexb(-/-) mice. CONCLUSIONS/SIGNIFICANCE: These results suggest that the FcRγ chain may render the usually poorly immunogenic thymus into an organ prone to autoimmune responses, including the chemotaxis of B1 cells toward CXCL13