More than an "inverted-U"? An exploratory study of the association between the catechol-o-methyltransferase gene polymorphism and executive functions in Parkinson's disease.

Executive dysfunction is common in Parkinson's disease (PD) patients. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to affect executive functions (EFs) in the prefrontal cortex. The present study attempted to explore the influence of the COMT polymorphism on EFs in patients with PD. Fifty-four PD patients were recruited and underwent neuropsychological assessments for three core EFs. The COMT polymorphism was genotyped using the TaqMan SNP Genotyping Assay. Participants were divided into three study groups: Val homozygotes, heterozygotes, and Met homozygotes. The three COMT genotype groups had significantly different performances in set-shifting [χ2 (2, 54) = 9.717, p = 0.008] and working memory tasks [χ2 (2, 54) = 7.806, p = 0.020]. Post-hoc analyses revealed that PD Val homozygotes performed significantly poorer in the set-shifting task than did either the PD Met homozygotes (z = -2.628, p = 0.009) or PD heterozygotes (z = -2.212, p = 0.027). Our explorative results suggest that the putative level of prefrontal dopamine influenced set-shifting through a "cane-shaped" dopamine level-response relationship. Our results have clinical implications, which may influence PD treatment with dopamine in the future because the optimal dopamine level to maximize EFs may vary based on the clinical course and COMT polymorphism status. Further study recruiting a larger number of participants is needed to confirm our preliminary findings.

[Differential Regulation of Bruton's Tyrosine Kinase by the Ubiquitin Pathway].

OBJECTIVE: To investigate the regulation of Bruton's tyrosine kinase (Btk) and to explore its possible mechanism. METHODS: After treatment with the proteasome inhibitors and/or phorbol esters (PMA), the mRNA and protein expression level of Btk was detected by RT-PCR and Western blot, respectively. The ubiquitination level of Btk in B lymphoblastoid A20 cells was estimated after stimulation via the crosslinking of BCR with anti-IgM antibody. The cotransfection of COS-7 cell with Btk, ubiquitin and Cbl was performed, then the ubiquitination level of Btk was measured. The Btk ubiquitination level was detected after ectopic expression of ubiquitin transfected with the wild type or triple mutant of Ub (K29R, K48R, K63R) . Mono-ubiquitination of Btk was detected with antibodies preferentially against monovalent ubiquitin; in addition, the protein expression levels of chloroquine-treated stably transfected cells expressing Btk-GFP were detected by Western blot, and quantified with the strength of GFP fluorescence. RESULTS: In the presence of proteasome-specific inhibitors and/or PMA, steady-state levels of Btk protein were reduced due to decrease of transcription. Posttranslational modification of Btk by ubiquitination was observed, which was related with the level of Btk expression and activation. The E3 ubiquitin ligase Cbl, which binds to Btk, was also found to ubiquitinate this kinase. Altogether, the data of this study strongly suggest that Btk is regulated by poly- and/or mono-ubiquitination events. CONCLUSION: The Btk protein is dictated by its expression level through the ubiquitination pathway.

[Establishment of Human Acute B-Lymphoblastic Leukemia--NOD/SCID Xenotransplant Mouse Model].

OBJECTIVE: To establish human B-acute lymphoblastic leukemia NOD/SCID mouse model. METHODS: The unirradiated mice aged 4-5 weeks were injected with Nalm-6 cells via the tail vein. Successful transplantation was assessed by the general state, bone marrow smear and histopathologic examination. RESULTS: After 15 days of injection with Nalm-6 cells, the NOD/SCID mice displayed the morbidily with lethargy, hind limb paralysis, hunched back and lossing weight. The infiltration of leukemia cells could be observed in bone marrow and spleen sections. CONCLUSION: Systemic B lineage acute leukemia animal mode1 has been successfully established in the NOD/SCID mice, which is a useful tool for studying pathogenesis of leukemia and guiding clinical chemotherapy regimens.