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V R Williams

Publications and source records attributed to V R Williams.

13 recordsLinked to original sources
PubMed1996

Tumour necrosis factor-alpha inhibits follicle-stimulating hormone-induced granulosa cell oestradiol secretion in the human: dependence on size of follicle.

This study investigated the effects of tumour necrosis factor-alpha (TNF) on human granulosa cells taken from ovaries of 11 premenopausal women undergoing oophorectomy during the luteal phase of the cycle for reasons unrelated to ovarian pathology. Granulosa cells from follicles ranging from 5-10 mm diameter (small) and from >10-25 mm (large) were subjected to culture for 48 and 96 h. Granulosa cells were cultured with human FSH (1 ng/ml), testosterone (1 microM) and human TNF (10 ng/ml), each alone, and in various combinations. In granulosa cells of small follicles, FSH alone increased progesterone and cAMP accumulation and the conversion of testosterone to oestradiol. In granulosa cells of large follicles, FSH increased progesterone and cAMP accumulation but not the conversion of testosterone to oestradiol. Only in granulosa cells of small follicles did TNF significantly inhibit FSH-induced conversion of testosterone to oestradiol but it was not apparent until the second 48 h of culture and concomitantly TNF did not alter the ability of FSH to stimulate progesterone and cAMP accumulation. In granulosa cells of large follicles, TNF did not alter FSH-stimulated oestradiol, progesterone or cAMP accumulation. Interestingly, progesterone accumulation in the presence of TNF and FSH was significantly greater in granulosa cells of large follicles than in granulosa cells of small follicles. The results indicate that TNF suppresses FSH-induced oestradiol secretion in granulosa cells from small follicles and this modulatory effect of TNF appears to be independent of decreases in progesterone and cAMP. The potential physiological significances of these findings is that TNF may be a relevant cytokine in suppressing FSH-induced oestradiol secretion and follicular growth during the luteal phase of the cycle.

Adult↗
PubMed1978

Combination chemotherapy: arriving at optimal treatment levels by incorporating side effect constraints.

This paper represents a method for determining optimal dose levels in a drug combination by analyzing the dose-response surfaces estimated from experimental data. In addition to using the presence or absence of a favorable response (in this instance, survival for at least twice the median untreated lifespan of B6D2F1 female mice bearing advanced sc implanted L1210 leukemia), the presence or absence of associated side effects is also employed (in this instance, Day-12 weight loss). The technique is potentially superior to existing methods of responding to the occurrence of treatment side effects due to its ability to take into account interactions between drugs. Since this method offers a way to determine optimal dose by including nonlethal toxicity information; it should find application in clinical situations.

Animals↗