Administration of Acts Act Amendment Act, 1979, No. 56

It has been suggested that childhood obsessive-compulsive disorder (OCD) may be a risk factor for the development of an eating disorder (ED) later in life, but prospective studies are lacking. We aimed to determine the prevalence of ED at follow-up and clinical predictors in a longitudinal clinical sample of adolescents/young adults diagnosed with OCD in childhood. All contactable (n=231) young people with OCD assessed over 9 years at a national and specialist paediatric OCD clinic were included in this study. At follow-up, 126 (57%) young people and parents completed the ED section of the Developmental and Well-being Assessment. Predictors for ED were investigated using logistic regression. In total, 16 participants (12.7%) had a diagnosis of ED at follow-up. Having an ED was associated with female gender and persistent OCD at follow-up. There was a trend for family history of ED being predictive of ED diagnosis. Five (30%) of those who developed an ED at follow-up had ED symptoms or food-related obsessions/compulsions at baseline. A difference in predictors for an ED versus other anxiety disorders at follow-up was identified. This study provides initial evidence that baseline clinical predictors such as female gender and family history of ED might be specific to the later development of ED in the context of childhood OCD. Clinicians should be alert to ED subthreshold symptoms in young girls presenting with OCD. Future longitudinal studies are needed to clarify the relationship between childhood OCD and later ED

悪性腫瘍における治療選択検査と分子標的治療の開発 : プリン代謝酵素欠損モデル

application/pdf核酸代謝とメチオニン代謝に関係するMethylthioadenosine phosphoryalse (MTAP)の異常(酵素欠損)は、多くの癌で高頻度に認められる。本研究では、MTAPタンパクの有無を診断する方法が遺伝子欠失診断より有用であることを証明した。MTAP酵素欠損とDNAメチル化の検討では、MTAP陰性細胞ではDNAメチル化が促進されることを確認し、発癌過程におけるepigenetic mechanismにMTAP酵素欠損も関与している可能性を新たに見出した。白血病におけるMTAP酵素欠損の診断法としてFACS analysisによる方法を開発した。これらの研究成果は、MTAP酵素欠損を分子標的とする選択的化学療法の実現に向かって大きなステップとなり、近い将来にはCompanion diagnosticsとして完成することが期待される。Methylthioadenosine phosphorylase (MTAP) is an enzyme involved in the metabolism of purine and methionine. Genetic analysis of the MTAP-negative cancer cell lines indicated that the all enzyme-negative cell lines but one had the partial or total deletion of MTAP gene. When this exceptional cell line was incubated with 5'-deazacytidine, the MTAP gene expression was confirmed by RT-PCR, indicating that the promoter hypermethylation is one of the mechanisms for MTAP deficiency in malignancy. In addition to IHC and Western blotting with anti-human MTAP monoclonal antibody, FACS analysis was found to be useful for the diagnosis of MTAP deficiency in leukemic cell lines.In conclusions, MTAP deficiency will be diagnosed more precisely with IHC and FACS analysis than with the genetic test alone. Since the frequency of MTAP deficiency in a variety of primary tumors is relatively high, one could exploit this metabolic difference between normal and cancer cells for the development of the selective chemotherapy. Furthermore, the combination of MTAP deficiency as a molecular target and the selective chemotherapy is a good example of companion diagnostics.平成20~22年度科学研究費補助金(基盤研究(B))研究成果報告書2039016