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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 415 records · Page 23Linked to original sources
PubMed1998

Differential labelling of laminin alpha 2 in muscle and neural tissue of dy/dy mice: are there isoforms of the laminin alpha 2 chain?

Laminin alpha 2, a sub-unit of the basement membrane component laminin-2, is deficient in the dy/dy and allelic dy2 J/dy2 J mouse. It is also the defective protein in a proportion of children with congenital muscular dystrophy. Linkage and mutational analysis have established that this is a primary effect caused by defects in the LAMA2 gene. Laminin alpha 2 has previously been shown to be deficient in dy/dy skeletal muscle, peripheral nervous system and brain. We report here preliminary observations on differences in detection of laminin alpha 2 in muscle, peripheral nerves and brain of dy/dy mice using three, well characterized antibodies. In normal muscle laminin alpha 2 is localized to the basement membrane of the myofibres and the Schwann cells of peripheral nerves, whilst in adult brain it is only detected on blood vessels. Our results show that there is appreciable, but slightly reduced, expression of laminin alpha 2 in skeletal muscle of dy/dy mice but almost no detectable protein in the brain, peripheral nerve and spinal nerve roots. Our observations are at present unexplained but they raise the possibility for the first time that there may be different tissue specific isoforms of laminin alpha 2. Molecular characterization of possible differences responsible for our observations may aid the identification of the mutation in the dy/dy mouse and lead to a better understanding of the role and expression of laminin alpha 2 in pathological conditions.

Animals↗
PubMed1998

Cytokine regulation of inducible nitric oxide synthase in vascular smooth muscle cells.

NO is an important mediator in sepsis. It has been unequivocally established that it is the major determinant in the vasodilatation and consequent hypotension in experimental animals following the administration of LPS. It is cytotoxic, particularly in combination with superoxide anions, and exerts negative inotropic and chronotropic effects on the heart. The exact role that these functions play in sepsis, however, remain unclear. Similarly, its immunomodulatory and cerebral effects, although potentially important, remain of uncertain significance in sepsis. Regulation of such a pivotal molecule is clearly extremely important: the data described here show that not only is this regulation extremely complex, but it appears to vary in different cell types. The implication of this finding for future clinical work is clear. NO production is not all bad: in some circumstances, it may be desirable to differentially regulate iNOS activity such that production is restricted in some cell types but not in others. The work described here begins to offer the possibility of identifying new molecular targets which allow this kind of differential regulation.

Animals↗
PubMed1998

Hemispheric titanium porous coated acetabular component without screw fixation.

One hundred fifteen hips in 108 patients with primary total hip arthroplasty using the anatomic porous replacement hemispheric acetabular component implanted without adjunctive screw fixation had a mean postoperative followup time of 6 years (range, 5-7.4 years). Clinical evaluation was performed using the Harris hip score and patient self assessment using a modified Short Form-36 questionnaire. Radiographs were measured for radiolucent lines, polyethylene wear, osteolysis, migration, and fractures. No acetabular metal shell had been revised for loosening or was radiographically loose with or without migration (more than 3 mm) at final followup. Reoperation was done in nine (8%) hips because of polyethylene insert wear or disassembly. No fracture of the acetabular bone occurred at the time of surgery or was observed on radiograph. Fixation of the metal shell was stable, with progressive radiolucent lines observed at final followup in 2% of the hips. Osteolysis was recorded in one patient with two acetabular components. The fixation of noncemented hemispheric porous coated acetabular components is more related to the technique of acetabular bone preparation and press fit implantation than to whether additional screws or peg fixation are used. Fixation of this acetabular component without screws at an average of 6 years after surgery is reproducible and predictable in primary hip arthroplasty. The design of modular polyethylene inserts has been improved and should reduce the wear rate of reoperations of the polyethylene insert.

Acetabulum↗
PubMed1998

A controlled evaluation of small-group education of general practitioners in the management of drug users.

We evaluated the effectiveness of small-group education of general practitioners (GPs) in the management of drug users. A total of 40 doctors were trained. Some 28 doctors who were unable to attend and 30 who did not want training participated as comparison groups. Sixteen months after the education, trained doctors notified significantly more drug users to the British Home Office database and more often prescribed methadone at first consultation with a drug user.

Education, Medical, Continuing↗
PubMed1998

Case report: chromatid exchange and predivision of chromatids as other sources of abnormal oocytes detected by preimplantation genetic diagnosis of translocations.

Preimplantation genetic diagnosis of translocations can be performed on first polar bodies (PB) at metaphase stage using FISH with whole-chromosome painting DNA probes. Here we report the use of this method in a couple in which the female was a carrier of a balanced translocation 46,XX,t(11;16)(q21;q22). This case unusual in that two polar bodies showed recombination events between the homologue chromosomes of 11 and 16 pairs, resulting in M-II oocytes with monovalent chromosomes having a normal and a derivative chromatid. For this type of case, PGD analysis on polar bodies cannot give a useful result, because, at the second meiotic division, either of these chromatids could remain in the oocyte, resulting in a normal, balanced or unbalanced embryo. PGD analysis on blastomeres can provide a solution. 11 previous cases of PGD of translocations performed by metaphase PB analysis are reviewed.

Abortion, Spontaneous↗
PubMed1997

Productive penetration of rotavirus in cultured cells induces coentry of the translation inhibitor alpha-sarcin.

Internalization of rotavirus in MA104 cells was found to induce coentry of alpha-sarcin, a toxin that inhibits translation in cell-free systems and to which cells are normally impermeable. Entry of the toxin, measured by inhibition of protein synthesis at early times after infection, correlated with virus penetration leading to expression of infectivity, since toxin entry (1) was induced only by trypsin-treated triple-layered virions, to a degree dependent on the toxin and the virus concentration; (2) correlated with the degree of permissivity of different cell lines to rotavirus infection; (3) was inhibited to a similar extent as infectivity by treatment of cells with neuraminidase; and (4) was inhibited by pre- or postadsorption incubation of the virus with neutralizing monoclonal antibodies to VP7 and VP4 (VP8*). Neither the virus infectivity nor the toxin coentry was significantly affected by treatment of cells with bafilomycin A1, an inhibitor of the vacuolar proton ATPase, indicating that both events are independent of the endosomal acid pH. Virus-like particles (VLP), composed of rotavirus proteins 2/6/7/4, but not 2/6/7 or 2/6, were able to induce toxin entry as efficiently as virions. Use of genetically modified VLP in combination with the toxin coentry assay, which measures entry through a productive pathway, should allow identification of the regions of the outer capsid proteins essential for rotavirus penetration.

Animals↗
PubMed1997

Phosphorylation of erythropoietin receptors in the endoplasmic reticulum by pervanadate-mediated inhibition of tyrosine phosphatases.

Erythropoietin (EPO) is the major hormone regulating the proliferation of erythroid precursors and their differentiation into erythrocytes. Ligand binding to the erythropoietin receptor (EPO-R), a member of the cytokine receptor family, triggers Tyr phosphorylation of the surface form of the receptor, presumably mediated by the Janus kinase (JAK) 2. To study whether non-surface EPO-R can be phosphorylated, Ba/F3 cells stably transfected with EPO-R were treated with pervanadate (PV), which is widely used as a potent tool to inhibit cellular protein Tyr phosphatases, thus resulting in enhanced Tyr phosphorylation of cellular proteins. PV treatment caused the EPO-R to undergo Tyr phosphorylation in a time-dependent and dose-dependent manner. PV-mediated Tyr phosphorylation of EPO-R occurred at several intracellular sites including the endoplasmic reticulum (ER), because both endoglycosidase H (endo H)-resistant EPO-R and the ER-retained EPO-R mutant (DeltaWS1 EPO-R) were Tyr phosphorylated in response to PV. Moreover, in metabolic labelling experiments, endo H-sensitive EPO-R was also phosphorylated. The phosphorylated fraction accounted for only 30-50% of the newly synthesized EPO-R, the fraction that normally exits from the ER. Tyr phosphorylation could not be detected on proteolytic fragments of the EPO-R, suggesting that this is a highly regulated process. Unlike the wild-type (wt) EPO-R, which was phosphorylated both on EPO binding and after inhibition of Tyr phosphatases by PV treatment, an EPO-R mutant (W282R EPO-R) that does not activate JAK2 was phosphorylated after PV treatment but not by EPO binding. Both EPO-R and JAK2 were phosphorylated with similar kinetics by PV treatment, suggesting that JAK2, as well as protein Tyr kinases different from JAK2, might mediate PV-dependent EPO-R phosphorylation. Furthermore the Tyr-phosphorylated ER-retained EPO-R mutant DeltaWS1 co-immunoprecipitated with JAK2 kinase, indicating that the EPO-R might interact with JAK2 while in the ER.

Animals↗