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Biomedical subjects

R Dickson

Publications and source records attributed to R Dickson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Biochemistry, cell biology and molecular biology of lipids of Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae is a powerful experimental system to study biochemical, cell biological and molecular biological aspects of lipid synthesis. Most but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of this unicellular eukaryote have been cloned, and many gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes, turnover and degradation of complex lipids, regulation of lipid biosynthesis, and linkage of lipid metabolism to other cellular processes. Here we summarize current knowledge about lipid biosynthetic pathways in S. cerevisiae and describe the characteristic features of the gene products involved. We focus on recent discoveries in these fields and address questions on the regulation of lipid synthesis, subcellular localization of lipid biosynthetic steps, cross-talk between organelles during lipid synthesis and subcellular distribution of lipids. Finally, we discuss distinct functions of certain key lipids and their possible roles in cellular processes.

Biological Transport↗
PubMed1998

Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer.

PURPOSE: This phase I study was performed to evaluate the safety and pharmacokinetics of escalating doses of Marimastat (British Biotech, Inc, Oxford, United Kingdom) in patients with advanced malignancies and to determine the phase II recommended dose to be used in subsequent studies. PATIENTS AND METHODS: A standard phase I design was used in this study, in which consecutive groups of three patients were treated with escalating doses of the study drug. Marimastat was administered orally at 25, 50, or 100 mg twice daily to consecutive groups of patients with advanced lung cancer. An additional three patients were added at the highest dose studied (100 mg orally twice daily) to assess whether the inflammatory polyarthitis observed at that dose level can be prevented by a concurrent administration of nonsteroidal antiinflammatory drugs (NSAIDS) and/or low-dose corticosteroids. Blood was drawn for safety monitoring, pharmacokinetic analysis, and plasma levels of metalloproteinase (MMP)-2 and MMP-9 (determined by zymography). A total of 12 patients were studied. RESULTS: The most significant toxicity at the highest dose studied (100 mg orally twice daily) was a symptomatic inflammatory polyarthritis that persisted for up to 8 weeks after discontinuation of the study drug and was dose-limiting. The estimated plasma elimination half-life of Marimastat was 4 to 5 hours. The mean maximum concentration (Cmax) at a reasonably well-tolerated dose (50 mg orally twice daily) was 196 ng/mL and was reached within 1 to 2 hours (Tmax) after administration. Areas under the curve (AUC) tended to correlate with the dose of Marimastat. Zymographic analysis of peripheral-blood ratios of activated proenzymatic forms of MMP-2 and -9 did not show any consistent patterns of change in MMP levels or in a degree of their activation during the course of treatment. CONCLUSION: Marimastat was well absorbed from the gastrointestinal tract, with high levels of the study drug detected in plasma within hours after drug administration. Plasma concentrations of Marimastat achieved at dose levels 2 and 3 (50 mg and 100 mg orally twice daily) were substantially higher than those required for MMP inhibition in vitro. The dose-limiting toxicity (DLT) was severe inflammatory polyarthritis, which seemed to be a cumulative toxicity.

Administration, Oral↗
PubMed1998

Putting evidence into practice.

A training module is described in which experienced health care managers from developing countries explore the challenges to be faced when attempting to use the results of systematic reviews of scientific studies on health care interventions in policy and practice.

Decision Making↗
PubMed1997

Retransplantation of patients with severe posttransplant hepatitis B in the first allograft.

BACKGROUND: The outcome of orthotopic liver transplantation (OLTX) in patients retransplanted for severe hepatitis B virus (HBV) in the first allograft has been poor due to high rates of HBV reinfection and even more aggressive disease in the second graft. Recent data suggest that hepatitis B immunoglobulin (HBIg) given after transplantation can be successful in delaying or preventing HBV reinfection in patients transplanted for chronic hepatitis B cirrhosis. We report the successful retransplantation of patients who developed recurrent or de novo hepatitis B after OLTXY. METHODS: Using similar HBIg regimens, two centers retransplanted seven patients after they developed recurrent or de novo hepatitis B in the first allograft. At retransplantation all seven patients were HBs antigen (Ag) positive; four patients were positive for HBeAg and HBV DNA by immunoblot assay, two patients were negative for HBeAg and HBV DNA, and one patient was positive for HBV DNA and negative for HBeAg. All patients were either HDV Ag or anti-HDV negative. One patient was anti-HCV positive. All patients received HBIg infusions after retransplantation to maintain serum anti-HBs levels >500 IU/L indefinitely. RESULTS: After retransplantation, six of seven patients are alive (86%): all are without evidence of HBV recurrence with serum negative for HBsAg, HBeAg, and HBV DNA by immunoblot assay. Liver biopsies are normal on routine studies with immunohistochemical stains for HBcAg and HBsAg also being negative. Mean follow-up of these six patients is 40.1 months (range 21-63 months). One patient (14%) developed HBV reinfection 7 months after his second transplant, in spite of maintaining target anti-HBs levels. He maintained stable liver function with minimal evidence of clinical hepatitis B, but died 8 months later from an unrelated stroke. CONCLUSIONS: We conclude that patients with recurrent or de novo hepatitis B after OLTX can be successfully retransplanted using aggressive immunoprophylaxis to prevent HBV reinfection. The failure of HBIg therapy in one patient underscores the need for other effective adjunctive anti-HBV modalities.

Adult↗
PubMed1997

The complexity of searching the literature.

The science of systematically reviewing literature has become a research process in its own right. The key word of course, is systematic. In the context of a systematic review this indicates that all possible sources have been comprehensively searched using a pre-defined search strategy designed to identify all relevant published and unpublished work. This paper illustrates the components of a comprehensive search, examines the yield of this approach and discusses the time and resource requirements for conducting the search. It uses as an example a recently completed systematic review. The paper goes on to discuss ways in which nurses can become more involved in conducting and using the results of good quality reviews.

Databases, Factual↗
PubMed1997

Mechanisms of DES carcinogenicity: effects of the TGF alpha transgene.

Inappropriate estrogen exposure during critical periods of development will cause numerous abnormalities in the female reproductive tract. Epigenetic effects on the expression of estrogen-regulated genes is proposed to be one of the mechanisms by which neonatal estrogen elicits teratogenic and carcinogenic effects. Of note is the existence of an integral relationship between the regulation of members of the epidermal growth factor (EGF) gene family and estrogen effects on the growth and differentiation of the reproductive tract. To determine whether the EGF gene family plays a critical role in mediating the pathogenic effects of estrogen, we have used transforming growth factor-alpha (TGF alpha) transgenic mice to investigate the effects of constitutive TGF alpha expression in the reproductive tract and whether TGF alpha would potentiate carcinogenesis induced by the potent estrogen, diethylstilbestrol (DES), and by the carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA). The animals were homozygous TGF alpha transgenic female mice from the MT42 line and the parental CD-1 outbred mice. Constitutive TGF alpha expression was found to augment the effects of both DES and DMBA in eliciting hyperplastic and differentiation changes in the reproductive tract. The presence of the TGF alpha transgene significantly increased the incidence of DES-induced vaginal adenosis, uterine endometrial hyperplasia, hypaspadia, and benign ovarian cysts. In addition TGF alpha potentiated the effects of DMBA in eliciting uterine polyps and benign ovarian cysts, and in the retention of Wolffian Duct remnants. However, the incidence of reproductive tract neoplasia was not promoted by the presence of the TGF alpha transgene. This study indicates that TGF alpha plays a role in the developmental and morphogenic events of both the Müllerian duct and urogenital sinus, and that deregulation is associated with pathogenesis of these tissues. Furthermore, the fact that constitutive expression of the TGF alpha did not substitute for DES as a reproductive tract carcinogen or act as a promoter of DES-induced uterine neoplasia suggest that DES carcinogenesis involves more than aberrant expression of this single growth factor.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Psycho-educational care for adults with cancer.

As part of our series featuring reviews from the NHS Centre for Reviews and Dissemination, this paper reports the key findings of a systematic review carried out by Devine and Westlake (1995) investigating the impact of programmes designed to improve the psychological and physical well-being of patients with cancer. Overall, the researchers suggest such programmes are beneficial for patients and nurses should be encouraged to support these interventions.

Adult↗