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Biomedical subjects

J Cooper

Publications and source records attributed to J Cooper.

At least 37 records · Page 2Linked to original sources

Rapidly evolving myopathy with myosin-deficient muscle fibers.

Five patients with rapidly evolving, severe weakness had an unusual myopathy with virtually complete loss of myosin in 5 to 40% of muscle fibers. Three of the 5 patients began to develop weakness 1 to 2 weeks after lung transplantation. The fourth became weak after a febrile illness. The fifth presented with diabetic ketoacidosis and weakness. All patients had received corticosteroid therapy. In all cases the weakness was progressive and led to severe disability, with respiratory failure in 4 patients. Initial diagnostic testing did not localize an underlying cause for the weakness. Creatine kinase was normal or minimally elevated. Electromyography generally showed mildly myopathic or nondiagnostic changes. However, muscle biopsy revealed numerous small angular fibers with no myosin ATPase staining at any pH. Immunocytochemical staining and ultrastructural studies confirmed a severe loss of myosin in many fibers. This rapidly evolving myopathy with myosin-deficient muscle fibers appears to be different clinically and pathologically from previously described syndromes involving rapidly progressive weakness. Slow recovery over a period of months is the most common outcome.

Adult

Brain-derived neurotrophic factor and neurotrophin-4 increase neurotrophin-3 expression in the rat hippocampus.

Hippocampal levels of mRNA encoding nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are rapidly induced by enhanced neuronal activity following seizures and glutamate or muscarinic receptor activation. However, the levels of neurotrophin-3 (NT-3) mRNA acutely decrease after limbic seizures suggesting that a different mode of regulation may exist for these neurotrophins. Here we show that BDNF and neutrotrophin-4 (NT-4), but not NT-3 itself, up-regulate NT-3 mRNA in cultured hippocampal neurons. In the rat hippocampus, the muscarinic receptor agonist, pilocarpine increased BDNF mRNA levels rapidly and those of NT-3 with a delay of several hours. Injection of BDNF into neonatal rats elevated NT-3 mRNA in the hippocampus which demonstrates that BDNF is able to enhance NT-3 expression in vivo. The regulation of NT-3 by BDNF and NT-4 enlargens the neurotrophic spectrum of these neurotrophins to include neuron populations responsive primarily to NT-3.

Animals

The Northwick Park Neck Pain Questionnaire, devised to measure neck pain and disability.

Neck pain is common in rheumatological practice. Assessment of outcome is difficult without objective measures. A neck pain questionnaire using nine five-part sections has been devised to overcome this problem. Forty-four rheumatology out-patients with neck pain were studied. Questionnaires were completed on days 0 and 3-5, and at 1 and 3 months. There was good short-term repeatability (r = 0.84, kappa = 0.62). Mean scores of each of the nine sections tended to rise with that of the pain section showing internal consistency. Questions on duration and intensity of pain were good indicators of a patient's global assessment. The questionnaire is easy for patients to complete, simple to score and provides an objective measure to evaluate outcome in patients with acute or chronic neck pain.

Adult

The human cytomegalovirus UL100 gene encodes the gC-II glycoproteins recognized by group 2 monoclonal antibodies.

In human cytomegalovirus (HCMV) the envelope glycoprotein complexes designated gC-II contain two immunologically and biochemically distinct glycoproteins. Monoclonal antibodies (MAbs) recognizing the gC-II glycoproteins have been divided into two groups based on the M(r) of the glycoproteins they recognize. We have now identified the HCMV UL100 gene as the gene encoding the gC-II glycoprotein recognized by the Group 2 MAbs. To do this, gC-II complexes were immunoaffinity purified and cleaved with cyanogen bromide (CNBr). CNBr peptides were separated by reverse phase high performance liquid chromatography (RPHPLC). Amino acid sequences which matched sequences found in the protein encoded by the HCMV UL100 gene were obtained from three purified peptides. To confirm the assignment we made synthetic peptides using amino acid sequence from the carboxyl terminus of the protein encoded by the UL100 gene. These peptides were used to make murine antibodies. The anti-UL100 antibodies immunoprecipitated gC-II complexes and were reactive with gC-II glycoproteins recognized by Group 2 MAbs in Western blotting. Several overlapping UL100 fusion proteins were expressed in E. coli. Only one of these fusion proteins was recognized by gC-II Group 2 MAbs. None of these UL100 fusion proteins were recognized by gC-II Group 1 MAbs. These data showed that the UL100 gene encoded the gC-II glycoprotein recognized by the Group 2 MAbs and that the epitope recognized by these antibodies was located between amino acids 315 to 372 at the carboxyl terminus.

Amino Acid Sequence

Use of double-replacement gene targeting to replace the murine alpha-lactalbumin gene with its human counterpart in embryonic stem cells and mice.

The mouse alpha-lactalbumin gene has been replaced with the human gene by two consecutive rounds of gene targeting in hypoxanthine phosphoribosyltransferase (HPRT)-deficient feeder-independent murine embryonic stem (ES) cells. One mouse alpha-lactalbumin allele was first replaced by an HPRT minigene which was in turn replaced by human alpha-lactalbumin. The end result is a clean exchange of defined DNA fragments with no other DNA remaining at the target locus. Targeted ES cells at each stage remained capable of contributing efficiently to the germ line of chimeric animals. Double replacement using HPRT-deficient ES cells and the HPRT selection system is therefore a powerful and flexible method of targeting specific alterations to animal genes. A typical strategy for future use would be to generate a null mutation which could then be used to produce multiple second-step alterations at the same locus.

Animals

Factor VII coagulant activity and antigen levels in healthy men are determined by interaction between factor VII genotype and plasma triglyceride concentration.

Ischemic heart disease is caused by a combination of and interaction between a number of genetic and environmental factors. In a study of a group of healthy men from the United Kingdom, such an interaction was identified between the levels of plasma triglycerides and genetic variation determining plasma levels of factor VII, a clotting factor that is associated with risk of ischemic heart disease. We previously reported a common genetic polymorphism of the factor VII gene that changes arginine at residue 353 to a glutamine (Arg353-->Gln) and showed that healthy men who carry the allele for Gln353 had lower plasma levels of factor VII coagulant activity. This association is strongly confirmed in a new sample. Compared with 301 men with the allele for Arg353, 63 men with one or two alleles for Gln353 had levels of factor VII coagulant activity that were 20% lower (97.8% [95% confidence interval (CI), 95.2% to 100.4%] and 78.2% [CI, 73.8% to 82.9%], respectively; P < .0001), with similar genotype-associated differences observed for levels of factor VII antigen. The 6 men who were homozygous for the Gln353 allele had mean levels of factor VII coagulant activity and antigen that were lower by 40% and 50%, respectively. In an assay using bovine thromboplastin, which is specific for the cleaved (activated) form of factor VII, they had levels lower by 60%, suggesting that the major effect of the Gln353 substitution is to reduce the proportion of the circulating zymogen that is activated.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles

Dietary fat induces changes in factor VII coagulant activity through effects on plasma free stearic acid concentration.

Previous studies have demonstrated activation of the contact system of coagulation and an increase in factor VII coagulant activity (VIIc) when citrated plasma is incubated in the presence of micellar stearate. The products of contact activation, factors XIIa and IXa, were responsible in this system for the activation of factor VII, thereby increasing factor VIIc. To obtain evidence that these in vitro interactions also operate in vivo, factor VIIc was examined in relation to plasma free fatty acid concentrations in five healthy individuals during the consumption of isocaloric high-saturated fat, high-unsaturated fat, and low-fat diets, each taken for 4 weeks in random order and separated by intervals of 12 weeks. For all but the final 3 days of each phase, subjects selected appropriate foods from prepared lists to meet the dietary requirements. Experimental diets of predetermined fat content and composition were fed on days 26 through 28 in each phase. Fat supplied on average 62% of energy in two of the experimental diets and less than 20% of energy in the third. On the final day of each dietary phase, the concentrations of the various free fatty acids and factor VIIc were measured before breakfast and at three 150-minute intervals thereafter. Plasma factor VIIc was, respectively, 6.5% and 13.1% of standard higher on the unsaturated and saturated fat diets than on the low-fat diet. Furthermore, the plasma concentration of stearic acid was strongly associated with factor VIIc (r = .58; P < .0001), and this relation remained significant (P = .003) after allowance for the plasma concentrations of palmitic, oleic, and linoleic acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Investigation of increased incidence in childhood leukemia near radio towers in Hawaii: preliminary observations.

Twelve children from the Waianae Coast, Hawaii, were diagnosed with acute leukemia from 1979 to 1990. The standardized incidence ratio (SIR) of 2.09 (95% confidence interval (CI) 1.08 to 3.65) indicates a significant increase. Seven cases occurred between 1982 and 1984 and were unusual in terms of sex, age, and type of leukemia. A case-control study (12 cases, 48 matched controls) explored risk factors, including parents' occupation, X-ray exposure, domestic smoking, family and medical histories, and distance of children's residence locations to low frequency radio towers. The odds ratio (OR) for having lived within 2.6 miles of the radio towers before diagnosis was 2.0 (95% CI 0.06 to 8.3). The clustering may have been a chance event, but because of its peculiar characteristics, we feel it should be noted.

Case-Control Studies

Total knee arthroplasty: evaluation of an acute care rehabilitation program.

This retrospective research was performed to evaluate the acute care rehabilitation program provided for patients receiving total knee arthroplasties in one institution. Included were 146 patients with unilateral arthroplasties and 40 patients with bilateral arthroplasties. Care and charge data, functional scores, and discharge disposition were documented for all subjects. The mean hospital days and associated charges were, respectively, 9.9 and $16,149 for unilateral arthroplasties and 11.9 and $23,594 for bilateral arthroplasties. Significant improvements in function (bed mobility, transfers, locomotion, and stairs) occurred during the course of rehabilitation. Over 96% of the patients were discharged home (either with or without services). Predictive of both discharge disposition and hospital charges were arthroplasty type, initial bed mobility score, and discharge transfer score. The results demonstrate differences associated with unilateral and bilateral surgeries, verify that functional changes accompany rehabilitation, and show that functional capacity has implications for charges and discharge disposition.

Activities of Daily Living

Molecular analysis of the immune response to human cytomegalovirus glycoprotein B. I. Mapping of HLA-restricted helper T cell epitopes on gp93.

Human cytomegalovirus (HCMV) is one of the most common causes of congenital infection leading to birth defects, and a leading cause of serious illness in patients with impaired cell-mediated immunity. Helper T cell (Th) responses to HCMV proteins are likely to be important in limiting viral replication and preventing disease. Previous studies from this laboratory have demonstrated that the amino-terminal 513 amino acids of HCMV glycoprotein B (gB) can stimulate both B and T cell responses in humans. In the present study, the proliferative responses of HCMV-specific Th clones to recombinant proteins and synthetic peptides were examined to identify four Th epitopes on gp93, which represents the amino-terminal 460 amino acids of the gB polypeptide. Using clones of known HLA restriction specificity from several donors, it was shown that each HLA class II allele preferentially associates with a different epitope on gB. Five clones from two different donors recognized an epitope in the region of amino acids 250 to 264 restricted by DR4Dw14, two clones from different donors recognized an epitope in the region of amino acids 420 to 434 restricted by DR7Dw17, two clones from different donors recognized an epitope in the region of amino acids 178 to 194 restricted by DQw1 and a single clone recognized an epitope in the region of amino acids 190 to 204 restricted by DPw4. Although all peripheral blood mononuclear cells (PBMCs) expressing a particular HLA class II allele were able to present the appropriate HLA-restricted gB peptide to gB-specific Th clones, not all individuals expressing a given HLA allele exhibited PBMC responses to the corresponding gB peptide. The HLA-related differences in Th recognition of specific epitopes on gB described in this report may have important implications in virus-host interactions and vaccine strategies.

Adult

Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth factors stimulate the phosphorylation of Nck and its association with autophosphorylated growth factor receptors. A panel of platelet-derived growth factor (PDGF) receptor mutations at tyrosine residues has been used to identify the Nck binding site. Here we show that mutation at Tyr-751 of the PDGF beta-receptor eliminates Nck binding both in vitro and in living cells. Moreover, the Y751F PDGF receptor mutant failed to mediate PDGF-stimulated phosphorylation of Nck in intact cells. A phosphorylated Tyr-751 is also required for binding of phosphatidylinositol-3 kinase to the PDGF receptor. Hence, the SH2 domains of p85 and Nck share a binding site in the PDGF receptor. Competition experiments with different phosphopeptides derived from the PDGF receptor suggest that binding of Nck and p85 is influenced by different residues around Tyr-751. Thus, a single tyrosine autophosphorylation site is able to link the PDGF receptor to two distinct SH2 domain-containing signaling molecules.

Amino Acid Sequence

High-dose adrenaline in adult in-hospital asystolic cardiopulmonary resuscitation: a double-blind randomised trial.

Forty intensive care unit patients requiring cardiopulmonary resuscitation were randomised to receive either the standard dose of adrenaline (1 mg every five minutes) or high-dose adrenaline (10 mg every five minutes). In the majority of patients, overwhelming sepsis was the major contributing factor leading to cardiac arrest. In this group of patients no difference could be detected in response to high-dose adrenaline compared with the standard dose. Although no side-effects were noted with this high dose of adrenaline, more investigation is required prior to its routine use in cardiopulmonary resuscitation.

Adult

Implementing computerized tracking at a community health center: challenges and solutions.

A computerized tracking system for both preventive care and chronic disease tracking was implemented at a community health center, using a PC based local area network interfaced with a mainframe scheduling and billing system. Initial database construction used downloads of historical billing data, but ongoing database maintenance is accomplished by using an optical mark-sense scanner to construct both billing and clinical tracking files from custom-designed encounter forms. In this way, expanded clinical data is collected with an actual reduction in manually keyed data, reducing the ongoing cost of the system.

Ambulatory Care Information Systems

Headache.

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Headache