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Biomedical subjects

K McGovern

Publications and source records attributed to K McGovern.

16 recordsLinked to original sources
PubMed2005

Tamoxifen for retroperitoneal fibrosis.

Retroperitoneal fibrosis is characterised by diffuse inflammatory proliferation of fibroblasts and the deposition of collagen fibrils throughout the retroperitoneum, especially in perivascular sites. This results in blockage of the ureters and other tubular retroperitoneal structures such as the vasculature and lymphatic channels. Left untreated, it typically follows a progressive and fatal course. The condition responds favourably to tamoxifen and several case reports describe an improvement in renal function on this therapy. This case report describes a subjective and objective functional improvement of lymphoedema secondary to retroperitoneal fibrosis with the use of tamoxifen.

Antineoplastic Agents, Hormonal↗
PubMed1996

An oligopeptide permease responsible for the import of an extracellular signal governing aerial mycelium formation in Streptomyces coelicolor.

Morphological differentiation in the filamentous bacterium Streptomyces coelicolor is believed to involve a mechanism of extracellular signalling that culminates with the formation of an aerial mycelium. We have identified a gene cluster designated bldK in which insertional and deletion mutations cause a block in aerial mycelium formation. Extracellular complementation experiments indicate that bldK defines a step in a cascade of extracellular signals; colonies of a bldK-mutant strain extracellularly complement bld261-mutant colonies, and are themselves extracellularly complemented by bldA- and bldH-mutant colonies. The bldK locus, which is located at 5 o'clock on the genetic map and within Asel fragment "N' on the physical map, consists of five adjacent open reading frames. These genes specify homologues of the subunits of the oligopeptide-permease family of ATP-binding cassette (ABC) membrane-spanning transporters. Because bldK mutations confer resistance to the toxic tripeptide bialaphos, it is inferred that BldK is an oligopeptide importer. We propose that the BldK transporter is responsible for the import of an extracellular signalling molecule produced under the control of the wild-type product of the bld261 gene. The BldK-imported signal, in turn, causes the production of a second extracellular signal molecule that depends on the products of bldA and bldH for its action.

ATP-Binding Cassette Transporters↗
PubMed1996

The role of computer-based simulation for training surgeons.

The effectiveness of computer based simulation (CBS) technology for training surgeons has yet to be determined. However, there is a body of research that demonstrates the effectiveness of this technology for other training applications. This research also indicates the substantial savings in cost, time, and effectiveness of simulation.

Clinical Competence↗
PubMed1996

Assessing a virtual reality surgical skills simulator.

The Institute for Defense Analyses (IDA) was contracted to perform a military standard task analysis of laparoscopic cholecystectomy, and to study the effectiveness of a virtual reality surgical skills simulator as a tool for surgical training and as a method for recording psychomotor behavior. This report describes the purpose of the study, its design, initial results, and implications for the field of medical education.

Cholecystectomy, Laparoscopic↗
PubMed1995

Steps toward healing: false memories and traumagenic amnesia may coexist in vulnerable populations.

Child abuse is surely the most agonizing psychological issue of our time. We decry the tendency to polarize around the either-or dichotomy of "recovered versus false memories," when both are likely to occur. Memory researchers seem to generalize from the mild, one-shot stressors of the laboratory to the severe repeated traumas reported by abused populations, an inferential leap that is scientifically dubious. Naturalistic studies show (a) some post-traumatic memory impairment (not just forgetting, but difficulty remembering in spite of repeated efforts); (b) dissociativity, such as emotional numbing, detachment, and the like; but also (c) increased suggestibility (Spiegel & Cardena, 1991). About 20% of the normal population is highly suggestible, and in these individuals it is trivially easy to show suggested amnesia, detachment, perceptual blocking, etc., as well as to suggest dramatically false memories. It is therefore vital to assess suggestibility and dissociativity in traumatized populations. Adult survivors of abuse may show both more false "memories" and more "false forgetting" than the normal population.

Adolescent↗
PubMed1991

Membrane insertion of the Escherichia coli MalF protein in cells with impaired secretion machinery.

The MalF protein is an integral membrane protein of Escherichia coli containing eight membrane-spanning stretches and a large periplasmic domain of approximately 180 amino acids. We have asked whether this protein is dependent for its membrane insertion on the bacterial secretion machinery specified by the sec genes. Using azide to inhibit the SecA protein and sec mutants to reduce the functioning of the machinery, we have studied the membrane assembly of MalF and beta-galactosidase and alkaline phosphatase fusions to MalF. In no case did we see an effect of reducing sec gene function on the insertion of MalF or fusion proteins. Selection for mutants that would cause internalization of a MalF-beta-galactosidase hybrid protein yielded no mutations in sec genes. Our results suggest that MalF can assemble in the membrane independently of the bacterial secretion machinery.

ATP-Binding Cassette Transporters↗
PubMed1991

Identification of a protein required for disulfide bond formation in vivo.

We describe a mutation (dsbA) that renders Escherichia coli severely defective in disulfide bond formation. In dsbA mutant cells, pulse-labeled beta-lactamase, alkaline phosphatase, and OmpA are secreted but largely lack disulfide bonds. These disulfideless proteins may represent in vivo folding intermediates, since they are protease sensitive and chase slowly into stable oxidized forms. The dsbA gene codes for a 21,000 Mr periplasmic protein containing the sequence cys-pro-his-cys, which resembles the active sites of certain disulfide oxidoreductases. The purified DsbA protein is capable of reducing the disulfide bonds of insulin, an activity that it shares with these disulfide oxidoreductases. Our results suggest that disulfide bond formation is facilitated by DsbA in vivo.

Amino Acid Sequence↗
PubMed1991

Decoding signals for membrane protein assembly using alkaline phosphatase fusions.

We have used genetic methods to investigate the role of the different domains of a bacterial cytoplasmic membrane protein, MalF, in determining its topology. This was done by analyzing the effects of MalF topology of deleting various domains of the protein using MalF-alkaline phosphatase fusion proteins. Our results show that the cytoplasmic domains of the protein are the pre-eminent topogenic signals. These domains contain information that determines their cytoplasmic location and, thus, the orientation of the membrane spanning segments surrounding them. Periplasmic domains do not appear to have equivalent information specifying their location and membrane spanning segments do not contain information defining their orientation in the membrane. The strength of cytoplasmic domains as topogenic signals varies, correlated with the density of positively charged amino acids within them.

ATP-Binding Cassette Transporters↗
PubMed1988

Genetic analysis of the membrane insertion and topology of MalF, a cytoplasmic membrane protein of Escherichia coli.

MalF is an essential cytoplasmic membrane protein of the maltose transport system of Escherichia coli. We have developed a general approach for analysis of the mechanism of integration of membrane proteins and their membrane topology by characterizing a series of fusions of beta-galactosidase to MalF. The properties of the fusion proteins indicate the following. (1) The first two presumed transmembrane segments of MalF are sufficient to anchor beta-galactosidase firmly to the inner membrane. (2) Hybrid proteins with beta-galactosidase fused to a presumed cytoplasmic domain of MalF have high beta-galactosidase specific activity; fusions to periplasmic domains have low activity. We propose therefore, that periplasmic and cytoplasmic domains of integral membrane proteins can be distinguished by the enzymatic properties of such hybrid proteins. In general, it appears that cleaved or non-cleaved signal sequences when attached to beta-galactosidase cause it to become embedded in the membrane, and this results in the inability of the hybrid proteins to assemble into active enzyme. Additional properties of these fusion proteins contribute to our understanding of the regulation of MalF synthesis. The MalF protein, synthesized as part of the malEFG operon of E. coli, is approximately 30-fold less abundant in the cell than MalE protein (the maltose-binding protein). Differential amounts of the fusion proteins indicate that a regulatory signal occurs within the malF gene that is responsible for the step-down in expression from the malE gene to the malF gene.

ATP-Binding Cassette Transporters↗