Biomedical subjects

W You

Publications and source records attributed to W You.

22 records · Page 2Linked to original sources

PubMed1992

Cosedimentation of pea root polysomes with the cytoskeleton.

When conventional, high ionic strength buffers were used for the isolation of polysomes from pea roots, only about 10% were retained in the detergent-insoluble pellet, and they were not degraded by endogenous RNase. A low ionic strength, cytoskeleton-stabilizing buffer increased retention to 60%, but polysomes were severely degraded. The RNase inhibitors, ribonucleoside-vanadyl complexes, heparin, KCl and ammonium sulphate lessened degradation but caused release, while Tris-HCl at 15-25 mM was able to prevent degradation without causing release. Cosedimentation of polysomes with the cytoskeleton is not an artefact of adsorption or trapping since isolated polysomes labelled through their nascent polypeptides and added to unfractionated tissue were not retained in the cytoskeletal pellet.

Buffers↗

PubMed1992

Pharmacokinetic and pharmacodynamic studies of the effect of ketoconazole on reproductive function in male rats.

A single oral dose (300 mg kg-1) of ketoconazole induced reversible immobilization of rat epididymal spermatozoa at 8-24 h after dosing. This occurred when the drug concentrations in cauda epididymal fluid and seminal plasma were at their peak (18.0 +/- 7.3 and 13.5 +/- 3.0 micrograms ml-1, respectively), and which was preceded by a peak plasma concentration (Cmax) of 64.82 +/- 2.47 micrograms ml-1 at 5.15 +/- 0.68 h (Tmax). In contrast, rete testis fluid collected from the same animals contained only minute amounts of ketoconazole (0.47 +/- 0.34 micrograms ml-1). Plasma testosterone concentration showed a sharp decline within 4 h of dosing, followed by a recovery from suppression, even after administration of a low dose (100 mg kg-1) which did not affect sperm motility. These findings suggest that ketoconazole gains access to the post-testicular sex organs and affects the mature spermatozoa therein much more readily than it affects testicular spermatogenesis. Synthesis and screening of compounds with a related molecular structure but which exhibit more pronounced spermicidal and less pronounced anti-androgenic effects are thus suggested in the hope that rapidly acting and reversible male contraceptives might be identified and developed.

Administration, Oral↗

PubMed1979

Chronic neutrophilic leukemia. Report of two cases and review of the literature.

Chronic neutrophilic leukemia is a rare, infrequently recognized, myeloproliferative disorder. It usually manifests as a leukemoid reaction, with mostly mature granulocytes in the peripheral blood, with rare to occasional immature forms, and sometimes with normoblasts. The clinical manifestations also include hepatosplenomegaly, elevated leukocytic alkaline phosphatase, elevated serum vitamin B12 and serum vitamin B12 binder ("R" fraction), and elevated serum uric acid. Distinction from a leukemegaly, the absence of sepsis, usually normal erythrocytic sedimentation, and the absence of fever. Leukemoid reactions may be associated with elevated serum vitamin B12 and uric acid, but the levels are usually lower than those found in chronic neutrophilic leukemia. Many patients have gouty symptoms, especially after treatment with Busulfan, and many have an unexplained hemorrhagic tendency, making major operations a risk. The authors add two cases to the 11 previously described.

Adult↗

PubMedDate not supplied

Bcl-2 and mdr-1 gene expression during doxorubicin-induced apoptosis in murine leukemic P388 and P388/R84 cells.

The induction of apoptosis by doxorubicin (DOX) alone or in the presence of efflux blockers, verapamil (VPL) or trifluoperazine (TFP), and of bcl-2 and mdr-1 gene expression was analyzed in murine leukemic P388 and doxorubicin resistant P388/R84 cells. Incubation with DOX (0.1-1 microM) for 24 hours induced apoptosis in sensitive cells but not in the resistant P388/R84 cells. Flow cytometric analysis of apoptosis by terminal dideoxynucleotidyl (TdT) assay showed that 1 microM DOX induced apoptosis in 70% of P388 cells and in less than 5% of P388/R84 cells. When P388/R84 resistant cells were co-incubated with DOX and efflux blockers (10 microM VPL or 15 microM TFP), enhanced cellular DOX accumulation was accompanied by apoptosis. Quantitative analysis of DNA fragmentation by 14C-thymidine incorporation and gel electrophoresis of fragmented DNA confirmed the results from TdT assay and showed enhancement of DOX-induced DNA fragmentation in the presence of efflux blockers (VPL or TFP). DOX + VPL and DOX + TFP combination treatments induced apoptosis in upto 55% and 83% of P388/R84 cells, respectively. mdr-1 mRNA and P-gp expression were not altered during DOX-induced apoptosis. The results suggest that in murine leukemic cells, down-regulation of bcl-2 mRNA expression occurs during DOX-induced apoptosis and it depends on the cellular drug retention determined by mdr-1/P-gp drug efflux.

Animals↗