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1.  Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population 
The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid amide hydrolase (FAAH) gene, one of the major degrading enzymes of endocannabinoids, is reportedly associated with anorexia nervosa (AN). We genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control participants in Japan. There were significant differences in the genotype and allele frequencies of c.385C>A between the AN and control groups. The minor 385A allele was less frequent in the AN participants than in the controls (allele-wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653–0.976, P = 0.028). When the cases were subdivided into lifetime restricting subtype AN and AN with a history of binge eating or purging, only the restricting AN group exhibited a significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557–0.922, P = 0.0094). Our results suggest that having the minor 385A allele of the FAAH gene may be protective against AN, especially restricting AN. This finding supports the possible role of the endocannabinoid system in susceptibility to AN.
PMCID: PMC4113271  PMID: 25077173
Anandamide; cannabinoid 1 receptor; eating disorder; endocannabinoid
2.  IL-12 Stimulates the Osteoclast Inhibitory Peptide-1 (OIP-1/hSca) Gene Expression in CD4+ T Cells 
Journal of cellular biochemistry  2009;107(1):104-111.
Immune cell products such as interferon (IFN)-γ and interleukin (IL)-12 are potent inhibitors of osteoclast formation. We previously characterized the human osteoclast inhibitory peptide-1 (OIP-1/hSca), a Ly-6 gene family member and showed IFN-γ modulation of OIP-1 expression in bone marrow cells. Whether, IL-12 regulates OIP-1 expression in the bone microenvironment is unclear. Real-time PCR analysis revealed that IL-12 treatment significantly enhanced OIP-1 mRNA expression in human bone marrow mononuclear cells. Because IL-12 induces IFN-γ production by T cells, we tested whether IFN-γ participates in IL-12 stimulation of OIP-1 gene expression in these cells. IL-12 treatment in the presence of IFN-γ neutralizing antibody significantly increased OIP-1 mRNA expression, suggesting that IL-12 directly regulates OIP-1 gene expression. Interestingly, real-time PCR analysis demonstrated that IL-12 induces OIP-1 expression (3.2-fold) in CD4+ T cells; however, there was no significant change in CD8+ T cells. Also, IL-12 (10 ng/ml) treatment of Jurkat cells transfected with OIP-1 gene (−1 to −1,988 bp) promoter-luciferase reporter plasmid demonstrated a 5-fold and 2.7-fold increase in OIP-1 gene promoter activity in the presence and absence of antibody against IFN-γ, respectively. We showed that STAT-1,3 inhibitors treatment significantly decreased IL-12 stimulated OIP-1 promoter activity. Chromatin immunoprecipitation (ChIP) assay confirmed STAT-3, but not STAT-1 binding to the OIP-1 gene promoter in response to IL-12 stimulation. These results suggest that IL-12 stimulates the OIP-1 gene expression through STAT-3 activation in CD4+ T cells.
PMCID: PMC2782485  PMID: 19259951
3.  Psychological and weight-related characteristics of patients with anorexia nervosa-restricting type who later develop bulimia nervosa 
Patients with anorexia nervosa-restricting type (AN-R) sometimes develop accompanying bulimic symptoms or the full syndrome of bulimia nervosa (BN). If clinicians could predict who might change into the bulimic sub-type or BN, preventative steps could be taken. Therefore, we investigated anthropometric and psychological factors possibly associated with such changes.
All participants were from a study by the Japanese Genetic Research Group for Eating Disorders. Of 80 patients initially diagnosed with AN-R, 22 changed to the AN-Binge Eating/Purging Type (AN-BP) and 14 to BN for some period of time. The remaining 44 patients remained AN-R only from the onset to the investigation period. Variables compared by ANOVA included anthropometric measures, personality traits such as Multiple Perfectionism Scale scores and Temperament and Character Inventory scores, and Beck Depression Inventory-II scores.
In comparison with AN-R only patients, those who developed BN had significantly higher current BMI (p < 0.05) and maximum BMI in the past (p < 0.05). They also scored significantly higher for the psychological characteristic of parental criticism (p < 0.05) and lower in self-directedness (p < 0.05), which confirms previous reports, but these differences disappeared when the depression score was used as a co-variant. No significant differences were obtained for personality traits or depression among the AN-R only patients irrespective of their duration of illness.
The present findings suggest a tendency toward obesity among patients who cross over from AN-R to BN. Low self-directedness and high parental criticism may be associated with the development of BN by patients with AN-R, although the differences may also be associated with depression.
PMCID: PMC2275291  PMID: 18267038
4.  Actinobacillus actinomycetemcomitans Toxin Induces Both Cell Cycle Arrest in the G2/M Phase and Apoptosis 
Infection and Immunity  1998;66(12):5980-5987.
We found that the culture supernatant of the periodontopathic bacterium Actinobacillus actinomycetemcomitans had a cytotoxic effect on several cell lines. In this study, we purified the toxin from the culture supernatant of A. actinomycetemcomitans Y4 by a four-step procedure: ammonium sulfate precipitation, POROS HQ/M column chromatography, polymyxin B matrix column chromatography, and Mono-Q column chromatography. The purified toxin gave two major bands of protein with molecular masses of 80 and 85 kDa upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The mechanism of cell death of the B-cell hybridoma cell line HS-72 was examined by observing changes in nuclear morphology, an increase in the proportion of fragmented DNA, and the typical ladder pattern of degraded chromosomal DNA, indicating the induction of apoptosis. Overexpression of human Bcl-2 suppressed apoptosis in HS-72 cells, indicating that the toxin from A. actinomycetemcomitans induces apoptosis by a Bcl-2-inhibitable mechanism. Flow cytometric analysis revealed that the toxin caused cell cycle arrest in the G2/M phase and apoptosis in HS-72 cells. In addition, aurintricarboxylic acid, a DNA endonuclease inhibitor, markedly decreased the percentage of apoptotic cells but had no effect on cell cycle arrest in the G2/M phase. Taken together, these findings suggest that the toxin from A. actinomycetemcomitans could mediate the development of periodontal diseases through cell cycle arrest in the G2/M phase and apoptosis in B lymphocytes of periodontal tissue.
PMCID: PMC108757  PMID: 9826381

Results 1-4 (4)