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Biomedical subjects

S Masters

Publications and source records attributed to S Masters.

14 recordsLinked to original sources
PubMed2000

Lineage-restricted function of nuclear factor kappaB-inducing kinase (NIK) in transducing signals via CD40.

CD40 signaling in B cells and dendritic cells (DCs) is critical for the development of humoral and cell-mediated immunity, respectively. Nuclear factor kappaB (NF-kappaB)-inducing kinase (NIK) has been implicated as a central transducing kinase in CD40-dependent activation. Here, we show that although NIK is essential for B cell activation, it is dispensable for activation of DCs. Such data provide compelling evidence that different intermediary kinases are used by different cellular lineages to trigger NF-kappaB activation via CD40.

Animals↗
PubMed2000

New treatments for advanced cancer: an approach to prioritization.

The allocation of funding for new anticancer treatments within the UK has not kept pace with demand. Clinicians find themselves restricted in the use of licensed drugs which they feel are in the best interests of individual patients. Against this, health authorities have a duty to ensure that scarce resources are used equitably to meet the needs of the local population as a whole. Differential levels of funding for new treatments across the country have led to concerns about rationing by postcode. This paper outlines an approach to the prioritization of new treatment for advanced cancer developed jointly by clinicians and health authorities in South London. The approach involves evidence reviews and consensus meetings. Existing and new treatments are rated on a four-point 'relative effectiveness scale', which takes account of the impact of the treatment on quality of life and on survival. The strength of evidence supporting each effectiveness rating is also classified. Health Authorities have used these ratings to determine overall funding levels, while leaving decisions on individual patients to the relevant Trusts.

Antineoplastic Agents↗
PubMed2000

The role of CD40-CD154 interactions in the regulation of cell mediated immunity.

CD40 is expressed on a diverse array of cell types from the hematopoietic and non-hematopoietic compartments. Within the hematopoietic compartment, CD40 is found constitutively expressed on B cells, dendritic cells (DC) and macrophages. The function of CD40 in B cells has been documented as being essential in the control of humoral immunity. In DCs and macrophages, CD40 has been shown to be important in the induction of antigen-presenting cell (APC) maturation and effector function. CD40 is also expressed on non-hematopoietic cells like keratinocytes, epithelial cells, and vascular endothelial cells and has been shown to be functionally important on these cell types.

Animals↗
PubMed1997

Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.

Growth factors can promote cell survival by activating the phosphatidylinositide-3'-OH kinase and its downstream target, the serine-threonine kinase Akt. However, the mechanism by which Akt functions to promote survival is not understood. We show that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates BAD in vitro and in vivo, and blocks the BAD-induced death of primary neurons in a site-specific manner. These findings define a mechanism by which growth factors directly inactivate a critical component of the cell-intrinsic death machinery.

3T3 Cells↗
PubMed1996

Hyperinsulinemia is common in family members of women with polycystic ovary syndrome.

OBJECTIVE: To determine whether disorders of insulin secretion are common in male and female family members of subjects with polycystic ovary syndrome (PCOS). DESIGN: Family study of siblings and parents of PCOS subjects (five families). All proband cases met the criteria of polycystic ovaries (PCO) by ultrasound (US) and hyperandrogenism. SETTING: University Reproductive Medicine Unit. PATIENT(S): Family members of PCOS subjects. INTERVENTION(S): Oral glucose tolerance testing (OGTT), insulin, and lipids were measured. Clinical examination including assessment of premature baldness in men and US of ovaries in female members. MAIN OUTCOME MEASURE(S): Insulin, lipids, and clinical parameters. RESULT(S): Hyperinsulinemia (69%) and hypertriglyceridemia (56%) was common in family members as were PCO in 79% of 24 females and premature baldness in men in 88% of eight subjects. CONCLUSION(S): Hyperinsulinemia is a potential metabolic and genetic marker for subjects who may be carriers of a familial tendency for PCO.

Adolescent↗
PubMed1995

Ethnic differences in insulin and glucose response to glucose between white and Indian women with polycystic ovary syndrome.

OBJECTIVE: To examine different patterns of glucose and insulin secretion in women (of both Indian and white ethnic backgrounds) with polycystic ovary syndrome (PCOS). DESIGN: A 75-g oral glucose tolerance test was performed in 11 subjects from each group. SETTING: Reproductive Medicine and Gynecological Clinics from The Queen Elizabeth Hospital, Woodville, South Australia, and King Edward the VIIIth Hospital, Durban, South Africa. PATIENTS: Couples were grouped as follows: Indian nonobese and obese PCOS, Indian nonobese and obese reference subjects, white nonobese and obese PCOS, white nonobese and obese reference subjects. MAIN OUTCOME MEASURE: Insulin and glucose in plasma after oral glucose testing. RESULTS: Indian PCOS and nonobese reference subjects had higher insulin responses than whites. The ethnic difference was less pronounced in obese women. There were no ethnic differences in glucose response. CONCLUSION: This study demonstrates that the ethnic background of subjects with PCOS needs to be considered in studies on the metabolic parameters in this condition.

Adolescent↗
PubMed1992

Effects of genetic, epigenetic, and environmental factors on taxol content in Taxus brevifolia and related species.

The demand for taxol, a promising cancer chemotherapeutic agent, far exceeds supply. Presently, taxol is derived from the bark of the Pacific yew, Taxus brevifolia, a small, slow-growing evergreen tree native to the northwestern United States. Knowledge of the distribution and magnitude of genetic and non-genetic sources of variation in taxol content in the genus Taxus is necessary if supply issues are to be met through plant harvesting. Analytical determinations of taxol, cephalomannine, and baccatin III in more than 200 trees representing several populations of T. brevifolia and other yew taxa indicate that (1) significant variation in taxane content exists among and within populations and species, (2) taxol levels exceeding those reported for T. brevifolia bark were found in shoots of individual trees from most taxa studied, and (3) the season in which samples are collected and handling procedures can influence taxane content.

Alkaloids↗
PubMed1985

Parasites and asthma--predictive or protective?

Most prevalence surveys (figures 1 and 2) suggest that asthma is less common in heavily parasitized countries, but case-control studies either show no association or an increase in parasitism in asthmatics. Studies which included egg counts suggest that asthmatics have a lower parasite burden than normals, compatible with the notion that asthma protects against parasitic infection, or vice versa. The completely contradictory findings of serum IgE in three studies do not help to elucidate any association or its mechanism. The available epidemiologic data neither refute nor support the theory that parasitic disease protects against or causes asthma. A more definitive answer might come from a comparison of asthma prevalence in heavily parasitized and parasite-free subjects, or from a prospective study of asthma incidence in two or more comparable communities where one population is naturally or therapeutically free of intestinal parasites. If an effective antihelminthic vaccine is developed, it would also be interesting to watch vaccinees for development of, or changes in, asthma symptoms, and to determine whether these findings correlate with vaccine-induced changes in IgE.

Adult↗
PubMed1985

Biliary sequelae of endoscopic sphincterotomy.

Twenty five patients were reviewed a mean of 36 months after successful endoscopic sphincterotomy for the removal of bile duct stones. All the patients had improved symptomatically but 20% had episodes of mild abdominal pain and a similar number had elevated serum gamma glutamyltranspeptidase activities (up to 3 times normal). In 12 patients (50%) biliary gas was demonstrated indicating reflux of duodenal contents. Clinical cholangitis did not occur. Aspiration liver biopsy revealed mild portal tract fibrosis and inflammation in patients with biliary reflux. Biliary reflux was significantly associated with mild upper abdominal pain (P less than 0.05). This study has shown that mild abnormalities of biliary function persist after endoscopic sphincterotomy. The long term consequence of these changes is unclear.

Adult↗
PubMed1980

Urothelial susceptibility to tumor cell implantation: influence of cauterization.

In an effort to determine whether transitional tumor cells will preferentially implant on the cauterized urothelial surface, a reproducible technique for cauterization of a portion of the murine bladder was established. This technique simulated a transurethral fulguration of a bladder tumor in humans. Transplantable tumor cells (1 X 10(6)) were placed transurethrally into the bladder of 50 mice. Twenty-five of these mice each had a portion of their bladder cauterized prior to insertion of tumor cells. Implantation with subsequent tumors occurred in 54% of mice with cauterization, in contrast to 12% of mice with an intact urothelial surface (P less than 0.005). Intravesical thio-tepa, mitomycin C, and cis-platinum were capable of significantly reducing the incidence of implantation. These results suggest that seeding may be a contributing factor to the high recurrence rate following endoscopic resection or fulguration of bladder tumors and that intravesical chemotherapy initiated shortly after surgery may reduce the incidence of implantation.

Animals↗