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Biomedical subjects

A Wong

Publications and source records attributed to A Wong.

At least 253 records · Page 14Linked to original sources

Involvement of prostaglandin synthetase in the peroxidative metabolism of diethylstilbestrol in Syrian hamster embryo fibroblast cell cultures.

The mechanism for induction of tumors by estrogens is still unresolved. Neoplastic transformation of Syrian hamster embryo fibroblasts by diethylstilbestrol (DES) suggests that established principles of chemical carcinogenesis may be involved. The Syrian hamster embryo fibroblast cells provide a system in which now the question can be asked whether the metabolic activation of DES is a prerequisite for its biological activity in this system. In this study, Syrian hamster embryo fibroblast cell cultures were shown to oxidatively metabolize DES to cis,cisdienestrol (Z,Z-DIES) which is a DES metabolite commonly found in vivo. The only other metabolic conversion of DES detectable in these cell cultures was the formation of the glucuronides of DES and Z,Z-DIES. Z,Z-DIES is formed more efficiently in incubations with rapidly growing cells than in cultures approaching confluence. When arachidonic acid was added to the medium, Z,Z-DIES formation was enhanced, whereas indomethacin added to the cell cultures inhibited the formation of this metabolite. These data suggest the involvement of prostaglandin synthetase in the oxidative metabolism of DES by Syrian hamster embryo fibroblast cells in culture and suggest that cooxidation may play a role for its biotransformation in whole cells. Moreover, since many competing metabolic pathways are available to DES in vivo, this present study adds important additional support to the hypothesis that metabolism of DES via a peroxidative route plays a role in its carcinogenicity.

Animals↗

Morphologic and neoplastic transformation of Syrian hamster embryo fibroblasts by diethylstilbestrol and its analogs.

A mammalian cell culture system using normal, diploid Syrian hamster embryo fibroblasts was used as a model to study the ability of diethylstilbestrol (DES) and related compounds to induce neoplastic transformation. Like benzo(a)pyrene, a known chemical carcinogen, DES (0.01 to 10 micrograms/ml) induces morphological transformation of Syrian hamster embryo fibroblasts in vitro; the transformed colonies were indistinguishable from colonies of benzo(a)pyrene-transformed cells. The morphologically transformed colonies derived from either benzo(a)pyrene- or DES-treated cells were tumorigenic when injected into newborn hamsters. At doses of 0.01 to 1 microgram/ml for 48 hr, DES did not inhibit or stimulate cell proliferation. Structural analogs of DES were also tested in the Syrian hamster embryo transformation system. Like DES, tetrafluorodiethylstilbestrol, dimethylstilbestrol, and cis,cis-dienestrol morphologically transformed Syrian hamster embryo cells. The transformation frequency of dimethylstilbestrol was much less than that of DES, tetrafluorodiethylstilbestrol, or cis,cis-dienestrol. Hexestrol, dimethoxydiethylstilbestrol, and trans,trans-dienestrol did not transform these cells. No correlation could be demonstrated between reported estrogenic potency of the compounds and their cell-transforming capacity. Structure-activity relationships developed for these chemicals suggest that metabolism via specific pathways plays a role in DES-induced cell transformation.

Animals↗

Diethylstilbestrol induces neoplastic transformation without measurable gene mutation at two loci.

The frequency with which diethylstilbestrol induces neoplastic transformation and somatic mutation was measured concomitantly in Syrian hamster embryo cells. While diethylstilbestrol was as active as benzo[a]pyrene in inducing transformation, it failed to induce mutations at two conventionally studied loci. These results suggest that diethylstilbestrol may transform cells in the absence of gene mutations.

Animals↗

Hereditary generalized juvenile polyposis associated with pulmonary arteriovenous malformation.

A 28-yr-old mother and her 10-year-old daughter with generalized juvenile gastrointestinal polypsis, arteriovenous (AV) malformations of the lung and severe digital clubbing are described. The AV malformations were documented by pulmonary angiography in both subjects, and generalized juvenile polyposis was confirmed histologically and radiographically. Since pulmonary AV malformations associated with juvenile polyposis has not been previously reported, a new hereditary syndrome is proposed.

Adult↗

SEM in service pathology: a review of its potential role.

New medical technology evolves through distinct phases. Initial technical proving is followed by a phase of detailed data recording, often with no detailed attempt to fill any specific service requirements. Next an attempt is made to establish correlations with other techniques and results, with a view to defining any unique attributes of the technology in particular fields. Detailed service-related applications are then worked out, but the final adoption of new instrumentation into clinical practice depends not only on the success of its technical performance, but also on its cost-effectiveness. This paper reviews studies of clinically-derived material from the viewpoint of a U.K. diagnostic pathologist. Detailed comparisons are drawn between the evolution of SEM on the one hand and of LM and CTEM on the other. An attempt is made to identify areas of practice in which SEM might make the greatest impact in the foreseeable future. It is proposed that paraffin-embedded tissue in pathology back files may provide a valuable source of investigative material for diagnostic SEM.

Animals↗

The historical development of federal involvement in health care.

In this historical summary of the federal role in health care, three time periods are described: 1) the late 1700's to 1940; 2) 1941 to 1964; and, 3) 1965 to the present. Significant legislation and federal programs are reviewed. The purpose of this overview is to provide health professionals with an historical perspective and to increase their knowledge of current and future events in the rapidly changing health care delivery system in the United States.

Delivery of Health Care↗

The metabolically mediated DNA damage and subsequent DNA repair by 4-chlorobiphenyl in Chinese hamster ovary cells.

The metabolism of [3H]-4-chlorobiphenyl (CB) by Chinese hamster ovary cell cultures resulted in the formation of lipophilic hydroxylated metabolites, trichloroacetic acid soluble conjugates and covalent macromolecular adducts. The major lipophilic metabolite was chromatographically similar to 4'-chloro-4-biphenylol. The intracellular macromolecules were fractionated into protein, RNA and DNA. Although protein was the major target of covalent interaction with [3H]-CB and contributes 85% of the macromolecular binding, the specific binding of [3H]-CB to DNA was 3.5 and 1.4 times higher than that observed for protein and RNA respectively. Incubation of the CHO cells with 10 mM CB, [3H]-thymidine and 10 mM hydroxyurea for 2.5 hr resulted in a 1.6 fold increase in unscheduled DNA synthesis. The data demonstrated that the readily metabolized CB congener not only reacts with mammalian cell macromolecules, including DNA, but the DNA damage can also be demonstrated by its subsequent repair.

Animals↗

The association of obesity with infertility and related menstural abnormalities in women.

Historical data from 26 638 20-to 40-year women were used to study the association between obesity and menstrual abnormalities including evidence of infertility. It was found that women with evidence of anovulatory cycles, ie, irregular cycles greater than 36 days, and hirsutism, were more than 30 lb (13.6 kg) heavier than women with no menstrual abnormalities after adjusting for height and age. The percentage of women with evidence of anovulatory cycles was 2.6 per cent for women less than 20 per cent overweight, 4.0 per cent for women 20-49 per cent overweight, 5.8 per cent for women 50-74 per cent overweight., and 8.4 per cent for women more than 74 per cent overweight Women with a single menstrual abnormality including cycles greater than 36 days, irregular cycles, virile hair growth with facial hair, or heavy flow were also significantly heavier than women with normal values for these factors. A longer duration of obesity was associated with facial hair. Another analysis found that teenage obesity was greater for never-pregnant married women than for previously pregnant married women and for women having ovarian surgery for polycystic ovaries than for women having ovarian surgery for other reasons. This also supports an association of obesity with anovulatory cycles. These findings showing evidence of abnormal ovulation, menstrual abnormalities and excess hair growth in obese women may be explained by the recent studies of others demonstrating an association between obesity and hormonal imbalances.

Adolescent↗