Modulation of CD72 by ligation of B cell receptor complex molecules on CD5+ B cells

B cells expressing CD5 also carry its ligand, CD72. As an approach to understanding the role of CD5 and CD72 on B cells, we have examined the association of CD72 with CD5 and slgM by modulation/co-modulation and capping/co-capping following ligation of these surface molecules with specific antibodies. Modulation and co-modulation were measured after 24 h, whilst capping was measured after 1 h. CD5 and slgM co-modulated each other, CD72 co-modulated with slgM and CD5, but anti-CD72 did not affect either slgM or CD5. CD5 and slgM co-capped each other, whilst CD72 failed to co-cap with either slgM or CD5. The CD5-induced co- modulation of CD72 was partially blocked by specific protein tyrosine kinase inhibitor, but not the slgM-induced co-modulation, Protein kinase C (PKC) inhibitors abrogated the anti-mu- but not the anti-CD5- triggered modulation of CD72, whereas PKC activators prevented the CD5- but not the slgM-induced 24 h modulation of CD72. None of these drugs was able to modify the anti-CD72-induced modulation of CD72. Our data suggest that CD5 is physically associated with slgM in the B cell receptor complex but not with CD72. Furthermore, from the effect of drugs on modulation, there appears to be different associations of CD72 with slgM and CD5. These two pathways differed in some respects, consistent with a co-stimulatory function of CD72 and CD5 in B cell activation.      

Proteus vulgaris agglutination by cystic fibrosis sera

The factor in sera of patients with cystic fibrosis (CF) and their parents which agglutinates Proteus vulgaris has characteristics similar to those of IgG antibody to this organism. Sera of patients without CF who have P. vulgaris infections agglutinate the organism similarly. At present there are too many false-positives in a control population for the test to be widely useful for heterozygote identification.     

Understanding the benefit of metformin use in cancer treatment

Biguanides have been developed for the treatment of hyperglycemia and type 2 diabetes. Recently, metformin, the most widely prescribed biguanide, has emerged as a potential anticancer agent. Epidemiological, preclinical and clinical evidence supports the use of metformin as a cancer therapeutic. The ability of metformin to lower circulating insulin may be particularly important for the treatment of cancers known to be associated with hyperinsulinemia, such as those of the breast and colon. Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR) signaling and protein synthesis. The evidence supporting a role for metformin in cancer therapy and its potential molecular mechanisms of action are discussed.     

Rab GTPases as regulators of endocytosis,targets of disease and therapeutic opportunities

Agola JO, Jim PA, Ward HH, BasuRay S, Wandinger‐Ness A. Rab GTPases as regulators of endocytosis, targets of disease and therapeutic opportunities. Rab GTPases are well‐recognized targets in human disease, although are underexplored therapeutically. Elucidation of how mutant or dysregulated Rab GTPases and accessory proteins contribute to organ specific and systemic disease remains an area of intensive study and an essential foundation for effective drug targeting. Mutation of Rab GTPases or associated regulatory proteins causes numerous human genetic diseases. Cancer, neurodegeneration and diabetes represent examples of acquired human diseases resulting from the up‐ or downregulation or aberrant function of Rab GTPases. The broad range of physiologic processes and organ systems affected by altered Rab GTPase activity is based on pivotal roles in responding to cell signaling and metabolic demand through the coordinated regulation of membrane trafficking. The Rab‐regulated processes of cargo sorting, cytoskeletal translocation of vesicles and appropriate fusion with the target membranes control cell metabolism, viability, growth and differentiation. In this review, we focus on Rab GTPase roles in endocytosis to illustrate normal function and the consequences of dysregulation resulting in human disease. Selected examples are designed to illustrate how defects in Rab GTPase cascades alter endocytic trafficking that underlie neurologic, lipid storage, and metabolic bone disorders as well as cancer. Perspectives on potential therapeutic modulation of GTPase activity through small molecule interventions are provided.     

蒙药益智温肾十味丸质量标准

目的:建立蒙药益智温肾十味丸的显微、薄层、理化鉴别方法和高效液相含量测定方法,提高其质量控制水平.方法:在显微镜下观察本品粉末,以种皮厚壁细胞、石细胞群和体壁碎片为指标,鉴别本品中益智、苦石莲、冬葵果和方海;提取挥发油,点样于硅胶GF254薄层板上,环己烷-乙酸乙酯(9∶1)展开,以标准药材为对照,鉴别本品中的益智;理化方法鉴别白硇砂中氯化铵和方海中碳酸钙.对荜茇中胡椒碱进行含量监控,用ODS填充的色谱柱,甲醇-水(77∶ 23)为流动相,343 nm波长下测定.结果:方法可有效鉴别本品中益智、苦石莲、冬葵果、方海和白硇砂5味药材,高效液相含量测定方法在0.040 4～0.282 8 μg线性良好(r=0.999 9),胡椒碱的平均回收率为98.1％,RSD 0.62％,含量限度为不得少于1.4 mg·g-1.结论:该方法可有效控制本品质量.