Current Issue : January - March Volume : 2016 Issue Number : 1 Articles : 5 Articles
CYP4Fs were first identified as enzymes that catalyze hydroxylation of leukotriene B4 (LTB4). CYP4F18 has an unusual expression\nin neutrophils and was predicted to play a role in regulating LTB4-dependent inflammation. We compared chemotaxis of wild type\nand Cyp4f18 knockout neutrophils using an in vitro assay. There was no significant difference in the chemotactic response\nto LTB4, but the response to complement component C5a increased 1.9ââ?¬â??2.25-fold in knockout cells compared to wild-type (P <\n0.01). This increase was still observed when neutrophils were treated with inhibitors of eicosanoid synthesis. There were no changes\nin expression of other CYP4 enzymes in knockout neutrophils that might compensate for loss of CYP4F18 or lead to differences\nin activity. A mouse model of dextran sodium sulfate colitis was used to investigate the consequences of increased C5a-dependent\nchemotaxis in vivo, but there was no significant difference in weight loss, disease activity, or colonic tissue my eloper oxidase between\nwild-type and Cyp4f18 knockout mice. This study demonstrates the limitations of inferring CYP4F function based on an ability to\nuse LTB4 as a substrate, points to expanding roles for CYP4F enzymes in immune regulation, and underscores the in vivo challenges\nof CYP knockout studies....
MHC...
HIV/AIDS is a public health problem especially in sub-Saharan Africa where majority of infections\nand deaths occur. Despite the large number of studies and efforts made in covering the data gap\nusing mathematical models, little is known on how model estimates are confounded by the transmission\nvariabilities that exist in stages of HIV progression. This work investigates the impact of\nincluding stages of HIV transmission in HIV/AIDS models. A deterministic HIV/AIDS model is developed\nand extended to include stages of HIV progression of infected individuals. Theoretical investigation\nof the models and numerical analyses indicate that the two models produce different\nestimates, with the model without stages producing lower estimates than the staged model. These\nresults call for a careful consideration in evaluating the efficiency of HIV/AIDS models that are\nused to estimate and project the burden of HIV/AIDS disease....
Psoriasis is a chronic skin disease in which genetics play a major role. Although many genome-wide association studies have been\nperformed in psoriasis, knowledge of the age at onset remains limited. Therefore, we analyzed 173 single-nucleotide polymorphisms\nin genes associated with psoriasis and other autoimmune diseases in patients with moderate-to-severe plaque psoriasis type I (earlyon set,\n<40 years) or type II (late-onset, �40 years) and healthy controls. Moreover, we performed a comparison between patients\nwith type I psoriasis and patients with type II psoriasis. Our comparison of a stratified population with type I psoriasis (...
Anti-M�¨ullerian hormone receptor, type II (AMHR2), is a differentiation protein expressed in 90% of primary epithelial ovarian\ncarcinomas (EOCs), the most deadly gynecologic malignancy.We propose that AMHR2 may serve as a useful target for vaccination\nagainst EOC. To this end, we generated the recombinant 399-amino acid cytoplasmic domain of mouse AMHR2 (AMHR2-\nCD) and tested its efficacy as a vaccine target in inhibiting growth of the ID8 transplantable EOC cell line in C57BL/6 mice\nand in preventing growth of autochthonous EOCs that occur spontaneously in transgenic mice. We found that AMHR2-CD\nimmunization of C57BL/6 females induced a prominent antigen-specific proinflammatory CD4+ T cell response that resulted\nin a mild transient autoimmune oophoritis that resolved rapidly with no detectable lingering adverse effects on ovarian function.\nAMHR2-CD vaccination significantly inhibited ID8 tumor growth when administered either prophylactically or therapeutically,\nand protection against EOC growth was passively transferred into naive recipients with AMHR2-CD-primed CD4+ T cells but not\nwith primed B cells. In addition, prophylactic AMHR2-CD vaccination of Tg MISIIR-TAg transgenic mice significantly inhibited\ngrowth of autochthonous EOCs and provided a 41.7% increase in mean overall survival.We conclude that AMHR2-CD vaccination\nprovides effective immunotherapy of EOC with relatively benign autoimmune complications...
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