Search PubMed⌕ Search

Biomedical subjects

J Cooper

Publications and source records attributed to J Cooper.

At least 253 records · Page 14Linked to original sources
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗