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Biomedical subjects

W Yu

Publications and source records attributed to W Yu.

At least 361 records · Page 20Linked to original sources

The risk of epithelial ovarian cancer in short-term users of oral contraceptives.

Short-term use (less than 1 year) or oral contraceptives has been associated with increased to slightly decreased risks of epithelial ovarian cancer in several studies. To determine what might account for a statistically significant 40% reduction in risk associated with as little as 3 to 6 months of use, a finding previously reported from the Cancer and Steroid Hormone Study, and to consider the implications for mechanisms of pathogenesis, the authors compared numerous characteristics of short-term users of oral contraceptives (41 cases, 412 controls) with those of never users (242 cases, 1,517 controls). The reduced risk among short-term users was consistently restricted to women who stopped using oral contraceptives for medical reasons, which were essentially side effects; there was little evidence of a protective effect among women who stopped for nonmedical reasons. Factors such as age, parity, family history of ovarian cancer, estrogen dose, history of sterilization, and latency (interval from first use) could not account for the finding. These analyses suggest that short-term use of oral contraceptives has little to no effect per se on reducing the risk of epithelial ovarian cancer and that side effects resulting in cessation of oral contraceptive use shortly after it was begun may be indicative of factors that are protective against the disease.

Adult↗

Chloroplast heteroplasmicity is stabilized by an amber-suppressor tryptophan tRNA(CUA).

Photosynthesis-deficient mutants of the green alga Chlamydomonas reinhardtii were previously shown to arise from nonsense mutations within the chloroplast rbcL gene, which encodes the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39). Photosynthesis-competent revertants of these nonsense mutants have often been found to be stably heteroplasmic, giving rise to both mutant and revertant cells during mitotic or meiotic divisions under nonselective growth conditions. It was proposed that the stable heteroplasmicity might arise from a balanced polymorphism of suppressor and wild-type alleles of a tRNA gene maintained within the polyploid chloroplast genome. In the present study, we have focused on determining the molecular basis for the heteroplasmicity of one such revertant, named R13-3C, which was recovered from the 18-7G amber (UAG) mutant. Restriction-enzyme analysis and DNA sequencing showed that the amber mutation is still present in the rbcL gene of the revertant strain. In contrast, DNA sequencing of the suspected tRNA(Trp) gene of the revertant revealed a mutation that would change its CCA anticodon to amber-specific CUA. This mutation was found to be heteroplasmic, being present in only 70% of the tRNA(Trp) gene copies. Under nonselective conditions, the suppressor mutation was lost from cells that also lost the revertant phenotype. We conclude that stable heteroplasmicity can arise as a balanced polymorphism of organellar alleles. This observation suggests that additional tRNA suppressors may be identified due to their heteroplasmic nature within polyploid genomes.

Animals↗

Localization of adenovirus DNA by in situ hybridization electron microscopy.

Biotinylated deoxyadenosine triphosphate (dATP) (Bio-7-dATP) and 3H deoxythymidine triphosphate (dTTP) labeled adenovirus DNA were hybridized in situ to thin sections of Lowicryl K4M-embedded and whole-mount extracted HeLa cells infected with adenovirus. The biotinylated probe was detected by exposing the extracted cells or sections to antibodies against biotin followed by colloidal gold-conjugated secondary antibodies and then critical-point dried while 3H-dTTP labeled probe by electron microscopic autoradiography. On Lowicryl K4M sections, gold particles and silver grains were mainly restricted in the nucleus. Furthermore, whole-mount results suggested that replicating adenovirus DNA is localized on the nuclear matrix of its host cell. In this paper, the described non-radioactive procedures for hybrid detection offered several advantages: a) rapid signal detection; b) superior morphological preservation and spatial resolution; c) precise localization; and d) on Lowicryl K4M sections, signal to noise equivalent to radiolabeling.

Acrylic Resins↗

Metabolism of host and viral mRNAs in frog virus 3-infected cells.

Treatment of purified frog virus 3 (FV3) with nonionic detergent and high salt released an endoribonucleolytic activity and confirmed earlier findings of a virion-associated endonuclease. This observation, coupled with evidence implicating host and viral message destabilization in herpesvirus and poxvirus biogenesis, raised the question of what role, if any, mRNA degradation plays in FV3 replication. To answer this question, Northern analyses of mock- and virus-infected cells were performed using probes for representative host and viral messages. These studies demonstrated that the steady state level of host messages progressively declined during the course of productive FV3 infection, whereas the steady state level of viral messages was not affected. To determine whether the decline in the steady state level of host mRNA was due to virus-induced degradation or to normal turnover coupled to virus-mediated transcriptional shut-off, actin mRNA levels were examined in mock- and virus-infected cells in the presence and absence of actinomycin D. Under these conditions, actin mRNA levels declined more quickly in actinomycin D-treated, virus-infected cells, than in mock-infected cells incubated in the presence of actinomycin D suggesting that the decline in the steady state level of actin mRNA was due to degradation. However, although it appears as if host message degradation is responsible for virus-mediated translational shut-off, the ability of heat-inactivated FV3 to block cellular translation without destabilizing cellular messages indicates that message degradation is not required for translational inhibition. As noted above, the degradation of early FV3 messages was not involved in controlling the transition from early to late gene expression. Furthermore, the presence of abundant, but nontranslated, early messages late in infection, coupled with the inefficient translation of late messages in vitro supported earlier suggestions that FV3 gene expression is controlled, at least in part, at the translational level. Taken together, these results suggest that FV3 regulates gene expression in a unique manner and may be a good model to examine the mechanics of translational control.

Animals↗

Breast cancer detection in relation to oral contraception.

Analyses of tumor size and breast cancer stage were used to determine whether biased detection of breast cancer could have materially influenced estimates of risk associated with use of oral contraceptives. In a population-based case-control study conducted from 1980-1982, surveillance for breast cancer by breast exams, but not mammography, was found to be strongly linked to use of oral contraceptives. Tumors were slightly smaller and less likely to be late-stage (TNM stage III or IV) in patients who had used oral contraceptives. The net effect of any diagnostic bias on advancing the date of cancer diagnosis, whether from breast exams or other sources, was estimated to be less than 8 weeks. This corresponds to spuriously increasing the risk of early-occurring breast cancer in oral contraceptive users by at most 2.4% (relative risk = 1.024).

Adult↗

Does vibration cause poststenotic dilatation in vivo and influence atherogenesis in cholesterol-fed rabbits?

Arterial post-stenotic dilatation (PSD) is a fusiform swelling immediately down-stream to a stenosis. It is characterized by the presence of turbulent blood flow and wall vibration which has been claimed by others to be causal by producing structural weakening. We tested the hypothesis that vibration causes PSD in vivo by attaching electromagnetic and pneumatic vibrators to the aortic wall in chronic rabbits. We also observed whether mechanical vibration of the aorta in vivo influenced the distribution of oil-red-O lesions during one percent dietary cholesterol feeding. Low mass vibration gauges were developed to measure the vibration. Electromechanical vibrators having a ceramic magnet slug within a coil supplied with 50 Hz were glued to the aorta of chronic rabbits and the vibration maintained for an average of 8 weeks. Despite greater amounts of energy imparted to the wall there was no dilatation or difference in oil-red-O staining from the controls. Five weeks vibration at 100 Hz and an amplitude equal to the normal diameter pulse also produced no dilatation. We conclude that vibration does not cause PSD in vivo and suggest that its cause is likely to involve the vascular muscle stimulated by the effect of turbulent flow on the endothelium.

Animals↗

[Normal radiographic appearance of the distal ends of the radius and ulna--a correlative radiographic and histologic slab study of the wrists in 50 infants].

Based on a correlative radiographic and histologic slab study of the wrists in 50 infants who died of unrelated diseases, the author's chief conclusions are as follow: 1) On the wrist radiograph of the infant, bone bark in the Ranvier's groove may appear as a "thorn-like" bony process on the margins of the metaphysis of the radius and ulna. 2) The radiographic appearance of the provisional zone of calcification at the distal ends of the radius and ulna are variable on radiographs of normal wrists, and familiarity with these variations precludes incorrect diagnosis. 3) The locations of the partially convex part of the provisional zone of calcification on the radiograph of the wrist correspond to where the vessels in the epiphyseal cartilage are located.

Calcification, Physiologic↗

Protection against cadmium toxicity in yeast by alcohol dehydrogenase.

A cDNA expression library from Schizosaccharomyces pombe was transformed into Saccharomyces cerevisiae to screen for genes capable of conferring cadmium resistance to S. cerevisiae cells. The cDNA library was cloned into the S. cerevisiae expression vector pDB20 which is designed to express cDNAs via the constitutively-expressed promoter of the gene for alcohol dehydrogenase I (ADH1). Terminator and polyadenylation signals are also provided by the ADH1 gene. Cadmium resistant colonies were shown to arise by a recombination event leading to the exchange of the S. pombe DNA with the chromosomal ADH1 gene and a consequent dramatic increase in the ADH1 gene expression due to the high copy number of the plasmid. The overexpression of ADH1 effectively buffered the cells for cadmium ions by formation of Cd-ADH.

Alcohol Dehydrogenase↗

Translational control of equine herpesvirus type 1 gene expression.

Translational control mechanisms modulate gene expression in a variety of cellular and viral systems. Using hypertonic conditions to block protein synthesis in vivo, we observed that the synthesis of several major equine herpesvirus type 1 proteins was selectively inhibited. Although sensitivity to hypertonic conditions was graded across a continuum, messages coding for proteins of 203, 130.5, and 31.5 kDa were significantly more resistant to higher salt concentrations in vivo than those coding for polypeptides of 148, 116, and 74 kDa. Similar results were observed in vitro when potassium acetate was used to block initiation. In addition, Northern blot analyses demonstrated that steady-state levels of cellular mRNAs declined beginning at about 6 hr after infection. Taken together, these results indicate that the expression of several major equine herpesvirus type 1 genes was controlled in part at the post-transcriptional level.

Acetates↗

Translational efficiency: iridovirus early mRNAs outcompete tobacco mosaic virus message in vitro.

Infection with the iridovirus, frog virus 3, results in the rapid inhibition of host cell protein synthesis and is correlated with activation of an eIF-2 kinase. Because phosphorylation of eIF-2 inhibits ternary complex formation and thus reduces the overall level of translation, it has been suggested that frog virus 3 messages escaped translational shut-off by outcompeting host messages for the remaining translational capacity of the cell. In this report, we show that frog virus 3 messages were more translationally competitive than highly efficient tobacco mosaic virus transcripts based on their relative resistance to inhibitors of initiation. This result strengthens the suggestion that the selective translation of frog virus 3 transcripts in virus-infected cells may be a reflection of their enhanced competitiveness.

Animals↗

The role of polymorphic HLA-DR beta chain residues in presentation of viral antigens to T cells.

The relative importance of 11 polymorphic positions in the HLA-DR7 beta 1 chain in T cell recognition of foreign antigens was investigated using transfectants expressing mutant DR7 beta 1 chains as APC for five rabies virus-specific T cell clones. The results indicate that multiple amino acids, located in both the beta-strands and alpha-helix of DR7 beta 1 in the model of a class II molecule, are involved in DR7-restricted T cell recognition of these antigens. Many of the substitutions appeared to reduce the affinity of an antigenic peptide for the mutant DR7 molecules but did not prevent binding. The heterogeneity of responses of the three G-specific T cell clones to presentation of the G11.3 peptide by several of the mutant DR7 molecules indicates that the T cell receptor (TCR) of each these clones requires a different view of the G11.3/DR7 complex and raises the possibility that the G11.3 peptide may bind to the DR7 molecule in more than one conformation.

Amino Acid Sequence↗