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Biomedical subjects

L Cooper

Publications and source records attributed to L Cooper.

At least 55 records · Page 3Linked to original sources

Estrogen replacement therapy and cognitive functioning in the Atherosclerosis Risk in Communities (ARIC) Study.

The association of estrogen replacement therapy (ERT) with cognitive functioning was assessed in 6,110 women aged 48-67 years participating in the Atherosclerosis Risk in Communities (ARIC) study, a multicenter longitudinal investigation. ERT was evaluated in relation to results of three cognitive tests (the Delayed Word Recall (DWR) Test, the Digit Symbol Subtest of the Wechsler Adult intelligence Scale-Revised (DSS/WAIS-R), and the Word Fluency (WF) Test) using data from the first follow-up visit of the cohort (1990-1992). No consistent associations were seen between ERT and either the DWR test or the DSS/WAIS-R after adjusting for age, education, and additional covariates previously found to be associated with cognitive function scores. Among surgically menopausal women aged 48-57 years, adjusted mean WF scores were slightly greater in ERT current users (mean WF 35.9) than in never users (mean WF 33.5) (p < 0.02); and within current users, adjusted WF scores increased with duration of ERT use. However, the finding that ERT was associated with a slightly higher level of performance on only one of three measures offers little support for the hypothesis that ERT has a major protective effect on cognitive function in women less than 68 years of age. The generalizability of these findings to older women who are more likely to experience cognitive decline and who may be using ERT for longer periods of time is limited by the relatively young age of the cohort.

Aged↗

Repeatability and validity of the Rose questionnaire for angina pectoris in the Atherosclerosis Risk in Communities Study.

Angina pectoris (AP) as determined by the Rose questionnaire was assessed in nearly 16,000 black and white men and women participating in the Atherosclerosis Risk in communities Study, a population study of cardiovascular disease in four communities. The questionnaire was administered at yearly intervals and estimates of repeatability were made. Validity was assessed indirectly by comparing Rose AP to risk factors, prevalent heart disease, medication use, and thickness of carotid artery walls as measured by B-mode ultrasound. Using kappa statistics for agreement of positive Rose AP determinations taken 1 year apart, white men show a higher level of agreement than white women (average kappa 0.36 for white men, 0.30 for white women), and whites show a higher level of agreement than blacks (average kappa 0.23 and 0.22 for black men and women, respectively). Rose AP that persists for more than one determination is associated with thicker carotid artery walls, greater amounts of cigarette smoking, greater prevalence of reported heart attack, and greater use of chest pain medications. A single determination of severe Rose AP is also associated with thicker carotid artery walls. These data suggest that multiple reports and the more severe grading of Rose AP (pain reported while walking on the level) are likely to indicate more severe disease; however, a single report using the Rose questionnaire appears valid, i.e., moderately associated with disease and risk factors, and appropriate for use in epidemiological studies.

Angina Pectoris↗

An H-YDb epitope is encoded by a novel mouse Y chromosome gene.

Rejection of male tissue grafts by genotypically identical female mice has been explained by the existence of a male-specific transplantation antigen, H-Y (ref. 1), but the molecular nature of H-Y antigen has remained obscure. Hya, the murine locus controlling H-Y expression, has been localized to delta Sxrb, a deletion interval of the short arm of the Y chromosome. In mice, H-Y antigen comprises at least four distinct epitopes, each recognized by a specific T lymphocyte clone. It has recently been shown that one of these epitopes, H-YKk, is a peptide encoded by the Y-linked Smcy gene, presented at the cell surface with the H-2Kk major histocompatibility complex (MHC) molecule. However, deletion mapping and the analysis of variable inactivation of H-Y epitopes has suggested that the Hya locus may be genetically complex. Here we describe a novel mouse Y chromosome gene which we call Uty (ubiquitously transcribed tetratricopeptide repeat gene on the Y chromosome). We identify the peptide WMHHNMDLI derived from the UTY protein as an H-Y epitope, H-YDb. Our data formally demonstrate that H-Y antigen is the product of more than one gene on the Y chromosome.

Amino Acid Sequence↗

Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control. The ARIC Study. Atherosclerosis Risk in Communities Study.

BACKGROUND AND PURPOSE: White matter lesions (WML) may result from cerebral hypoperfusion or ischemia. We investigated the association of WML with blood pressure, hypertension, and its treatment and control. METHODS: A random sample of 1920 participants aged 55 to 72 years in the Atherosclerosis Risk in Communities Study (ARIC) was examined. Spin-density 1.5-T MRI scan images were coded from 0 for normal to 9 for most severe WML. Hypertension was defined as systolic or diastolic pressure > or = 140/90 mm Hg or use of antihypertensive medication. RESULTS: The percentages of persons with WML grades 0 through 2 and 3 through 9, respectively, were as follow: normotensive, 92.4% and 7.6%, versus all hypertensive subjects, 83% and 17% (P < .001); and treated controlled hypertensive, 86% and 14%, versus treated uncontrolled hypertensive subjects, 76% and 24% (P = .003). Multivariable adjusted odds ratios (95% confidence intervals) for WML grade > or = 3 relative to normotensive subjects was 2.34 (1.71 to 3.20) for all hypertensives, 1.99 (1.19 to 3.08) for untreated hypertensives, 1.94 (1.32 to 2.85) for treated controlled hypertensives, and 3.40 (2.30 to 5.03) for treated uncontrolled hypertensives. After additional adjustment for hypertension duration, treatment, and control status, the odds ratios (95% confidence intervals) for a 1 SD increase of systolic and diastolic blood pressure were 1.43 (1.11 to 1.85) and 1.16 (0.94 to 1.43), respectively. CONCLUSIONS: Hypertension is associated with increased odds of WML, and treated uncontrolled hypertensive subjects have greater odds of WML than those with treated controlled hypertension. The data suggest that the level of blood pressure, especially systolic blood pressure, is related to WML, additional to the effects of categorically defined hypertension and its treatment and control status.

Aged↗

Preparation for management: an exploratory study to ascertain perceptions of F grade nurses and clinical nurse managers.

This paper reviews relevant literature and discusses the results of a small study designed to investigate how nurses are responding to the changes in the structure of the NHS which have reduced their role in management. The findings suggest that nurses who are currently at F grade level and their clinical nurse managers (CNM) are aware of the need for nurses seeking career progression to participate in education and training programmes related to nursing and management, particularly those which provide recognized qualifications, and that many are currently striving to achieve this. The findings also suggest that nurses want support to enable them to undertake further study, but that due to increasing pressure of work it is becoming more and more difficult for CNMs to provide the level of support they consider helpful. Nurses and CNMs urge those developing courses in management to ensure that courses are flexible to enable varying types of participation and tailoring to individual needs.

Attitude of Health Personnel↗

Population awareness and control of hypertension and hypercholesterolemia. The Atherosclerosis Risk in Communities study.

BACKGROUND: A national program for hypertension detection and control was implemented in the 1970s, whereas a similar program for control of hypercholesterolemia has been implemented in recent years. We studied the levels of awareness, treatment, and control of these conditions in US population samples during a 3-year period (1987 to 1989). METHODS: The levels of awareness, treatment (by medication), and adequate control of hypertension (systolic blood pressure, > or = 140 mm Hg; diastolic blood pressure, > or = 90 mm Hg; or antihypertensive medication) and hypercholesterolemia (serum cholesterol level, > or = 6.21 mmol/L [> or = 240 mg/dL], or lipid-lowering medication) were studied among participants in the baseline examination of the Atherosclerosis Risk in Communities Study, including 15,739 individuals aged 45 to 64 years. RESULTS: Eighty-four percent of the hypertensive subjects and 42% of the hypercholesterolemic subjects were aware of their conditions. Overall, 50% of the hypertensive subjects and only 4% of the hypercholesterolemic subjects had their conditions both treated and controlled. Rates of hypertension prevalence, awareness, and control remained stable during the 3-year study period. Hypercholesterolemia prevalence decreased from 30% in 1987 to 25% in 1989; its awareness increased from 31% to 50% during the same period. Hypertensive women were more likely than hypertensive men to be aware and treated, whereas hypercholesterolemia awareness was higher in men than in women. Hypertension awareness was highest in black women, but black hypertensive subjects were less likely than whites to be treated and to have their hypertension controlled. Black hypercholesterolemic subjects were less likely to be either aware or treated. CONCLUSIONS: After the recent implementation of the National Cholesterol Education Program, the levels of awareness, treatment, and control of hypercholesterolemia are improving at a high rate, although they are still substantially lower than those for hypertension. Further improvement is necessary, particularly among certain population groups, such as blacks.

Age Distribution↗

Interplay between the human TCR/CD3 epsilon and the B-cell antigen receptor associated Ig-beta (B29).

T and B lymphocytes are characterized by the surface expression of highly variable antigen receptors called the T-cell (TCR) and B-cell (BCR) receptor. In both B and T cells, binding of antigen to their respective surface receptors results in transmembrane signaling which leads either to programmed cell death or to proliferation and differentiation. The human and murine TCR consist of the highly variable TCR alpha and beta or gamma and delta chains recognizing antigen and the non-covalently associated invariable CD3 complex (gamma, delta, epsilon) and zeta. The antigen-recognizing surface membrane-bound immunoglobulin (Ig) molecules on the surface of human and murine B cells are non-covalently associated with a heterodimeric protein complex of Ig-alpha (MB-1) and Ig-beta (B29). Like the CD3 complex associated with TCR the Ig-associated proteins are predicted to regulate the assembly and transport of the Ig complex to the cell surface and to couple membrane-bound Ig to intracellular signal transduction pathways. To gain more insight into structure/function relationships between CD3 proteins and Ig-alpha and Ig-beta, we transiently co-transfected pairs of expression vectors encoding either TCR/CD3 chains on the one hand and Ig-alpha or Ig-beta on the other into Cos cells. Thus we found a very strong interaction between CD3 epsilon and Ig-beta mediated by the extracellular domains. Experiments in which we could stain Jurkat T cells with soluble Ig-beta but not Ig-alpha protein indicated the recognition of CD3 epsilon by Ig-beta even in the context of the whole TCR/CD3 complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos.

Mutations in the human SRY-related gene, SOX9, located on chromosome 17, have recently been associated with the sex reversal and skeletal dysmorphology syndrome, campomelic dysplasia. In order to clarify the role of this gene in skeletal development, we have studied the expression of mouse Sox9 during embryogenesis. Sox9 is expressed predominantly in mesenchymal condensations throughout the embryo before and during the deposition of cartilage, consistent with a primary role in skeletal formation. Interspecific backcross mapping has localized mouse Sox9 to distal chromosome 11. The expression pattern and chromosomal location of Sox9 suggest that it may be the gene defective in the mouse skeletal mutant Tail-short, a potential animal model for campomelic dysplasia.

Amino Acid Sequence↗

Replacement of the active-site cysteine residues of DsbA, a protein required for disulfide bond formation in vivo.

DsbA is a periplasmic protein of Escherichia coli that was identified genetically as being involved in the formation of disulfide bonds in secreted proteins. Its active site contains one accessible and one buried cysteine residue, separated in the primary structure by only two other residues. These cysteine residues can form a very unstable disulfide bond that is 10(3)-fold more reactive toward thiols than normal. Moreover, the mixed disulfide between the accessible cysteine residue and glutathione is 10(4)-fold more reactive than normal. Site-directed mutagenesis was carried out to replace either one or both cysteine residues by serine. Cys30 is shown to be the accessible thiol, while Cys33 is shielded from the solvent. Even though the thiol group of Cys30 is exposed and reactive, it formed a very unstable mixed disulfide with glutathione. This disulfide bond was 2.17 +/- 0.02 kcal mol-1 less stable in the native conformation than when DsbA was unfolded. If the native conformation destabilizes the mixed disulfide, the mixed disulfide must destabilize the folded conformation to the same extent. This was confirmed by demonstrating that the folded conformation of the mixed disulfide form of the mutant DsbA was 2.7 +/- 0.9 kcal mol-1 less stable than that of the reduced form; these stability effects originated almost exclusively in the folded conformation. Replacing the cysteine residues by serine destabilized the folded conformation of the reduced protein to varying extents. This suggests that the thiol groups are involved in interactions that stabilize the folded conformation, which would cause any disulfide bonds, either inter- or intramolecular, that involve these groups to be unstable.

Base Sequence↗

DNA probes for identifying the members of the Anopheles punctulatus complex in Papua New Guinea.

Genomic DNA probes were made for five members of the Anopheles punctulatus complex of mosquitoes found in Papua New Guinea. Specific DNA probes were developed for An. punctulatus, An. koliensis, and three sibling species, An. farauti No. 4, An. farauti No. 5, and An. farauti No. 6, by differentially screening total genomic DNA libraries of individual species and sibling species with homologous DNA against heterologous DNA labeled with 32P. Probes ranged from 273 to 630 bp. Identification of species can be made from squash or dot blots using only a segment of the mosquito (i.e, head, thorax, abdomen, or even legs), allowing for concurrent analysis of the remainder of the mosquito for other epidemiologic characteristics.

Animals↗

On the biosynthesis of bovine pancreatic trypsin inhibitor (BPTI). Structure, processing, folding and disulphide bond formation of the precursor in vitro and in microsomes.

The natural gene for bovine pancreatic trypsin inhibitor (BPTI) was expressed by in vitro transcription/translation systems as the 100-residue pre-proBPTI, with a signal peptide for translocation into the endoplasmic reticulum. Expression in the presence of microsomes defined the site of co-translational cleavage of the signal peptide. The resulting proBPTI in the microsomes consists of the 58 residues of mature BPTI, plus an additional 13 residues at the N terminus, including a cysteine residue at position -10, and seven residues at the C terminus. ProBPTI remained in the unfolded, reduced form within microsomes when synthesized under reducing conditions, but folded and formed disulphide bonds rapidly when the disulphide form of glutathione was added. Complete folding could occur within about one minute, even when residue Cys10 was replaced by Ser. The structure of proBPTI was determined by circular dichroism and two-dimensional NMR and found to be that of mature BPTI with flexible extensions on both termini. Its inhibition of the activity of alpha-chymotrypsin was indistinguishable from that of the mature protein. The extensions of the precursor appeared to play only very minor roles in refolding in vitro under conditions where folding and disulphide bond formation are coupled. Under pH and redox conditions thought to reflect those in vivo, complete folding and disulphide bond formation required several hours. Addition of protein disulphide isomerase to in vitro folding experiments caused substantial and similar increases in the rate of formation of the fully folded state for both mature BPTI and proBPTI; the half time for folding to the native state was reduced to approximately two minutes, which is comparable to that occurring in microsomes. The absence of substantial effects of the N and C-terminal extensions on the protein structure, inhibitor activity and refolding leaves their functional roles to be discovered.

Amino Acid Sequence↗

Behavioral problems among twins.

Despite the frequency of multiple births, little information is available to assist parents and health professionals in the identification and management of behavior problems in multiple-birth siblings. Three case reports are presented that describe quarreling, aggression, and feeding problems among twins. To develop intervention strategies most appropriate for the problem behavior, it is important to determine whether (1) parents are able to effectively implement the intervention strategy, (2) behavior is isolated to one sibling, and (3) different reasons are responsible for similar behavior in siblings. Structured observations were used to determine whether the undesired behavior occurred to escape nonpreferred activities, gain access to preferred activities, or obtain parental attention. The cases provide a framework to facilitate the identification and management of common behavior problems occurring among multiple-birth siblings.

Child Behavior Disorders↗

Comparison of diazepam with progestin for effectiveness in suppression of urine spraying behavior in cats.

The most common treatment for urine spraying and marking in cats has been administration of long-acting progestins. Treatment with diazepam has recently been gaining favor, particularly because of reported adverse effects of progestins. Results of a clinical trial involving 20 cats indicated that diazepam was effective in eliminating or markedly reducing spraying in 11 (55%) of them. However, most cats required continuous treatment, or at least intermittent treatment, when spraying recurred. The physiologic and behavioral dependency of cats on diazepam, which presumably develops over the course of administration, may contribute to the tendency for spraying to recur once diazepam treatment is discontinued. Using data from previously published findings on progestin administration, plus additional cases, it was documented that a significantly (P less than 0.05) higher percentage of males than females responded favorably. Although the number of cases was not sufficient for a statistical comparison of diazepam vs progestin treatment with regard to male vs female, possible gender difference in the effectiveness of diazepam was not indicated.

Animals↗

Cloning and sequencing of the cDNA encoding the human homologue of the murine immunoglobulin-associated protein B29.

Membrane-bound immunoglobulins (Ig) on the surface of murine B cells are noncovalently associated with a heterodimeric protein complex of MB-1 and B29 (also called Ig-alpha and Ig-beta). The Ig-associated proteins are predicted to regulate the assembly and transport of the Ig complex to the cell surface and to couple membrane-bound Ig to intracellular signal transduction pathways. We have isolated and sequenced a full-length cDNA clone encoding the human homologue of the B29 protein. The predicted amino acid sequence was compared to its murine counterpart, to MB-1 and to the human T cell receptor (TcR)-associated CD3 proteins. The alignment of the human B29 protein with its murine counterpart revealed 90% homology in the C-terminal portion comprising the cytoplasmic tails, the transmembrane regions and the adjacent 26 amino acids of the extracellular regions. Only 59% homology was found in the rest of the Ig-like extracellular domains. The high degree of conservation observed for the C-terminal amino acids suggested that these domains of the proteins play important functional roles for the Ig complex. Indicative of this was the conservation of the antigen receptor tail motif D-(X)7-E/D-(X)2-Y-(X)2-L-(X)7-Y-(X)2-L/I which is thought to be a component of signal transduction pathways. This motif is also found in the human and murine MB-1 proteins as well as in the TcR-associated CD3 molecules. Further regions of homology between B29, MB-1 and the CD3 proteins included extracellular residues which were predicted to maintain the Ig-like structure, and hydrophilic residues within the transmembrane regions which may be utilized during the intracellular assembly and transport of the oligomeric Ig/MB-1/B29 or TcR/CD3 complexes. Thus the similarities found between B29, MB-1 and the CD3 proteins suggest conserved functions for both the Ig- and TcR-associated proteins.

Amino Acid Sequence↗

The Anopheles punctulatus complex: DNA probes for identifying the Australian species using isotopic, chromogenic, and chemiluminescence detection systems.

Isotopic and enzyme-labeled species-specific DNA probes were made for the three known members of the Anopheles punctulatus complex of mosquitoes in Australia (Anopheles farauti Nos. 1, 2, and 3). Species-specific probes were selected by screening total genomic libraries made from the DNA of individual species with 32P-labeled DNA of homologous and heterologous mosquito species. The 32P-labeled probes for A. farauti Nos. 1 and 2 can detect less than 0.2 ng of DNA while the 32P-labeled probe for A. farauti No. 3 has a sensitivity of 1.25 ng of DNA. Probes were then enzyme labeled for chromogenic and chemiluminescence detection and compared to isotopic detection using 32P-labeled probes. Sequences of the probe repeat regions are presented. Species identifications can be made from dot blots or squashes of freshly killed mosquitoes or mosquitoes stored frozen, dried, and held at room temperature or fixed in isopropanol or ethanol with isotopic, chromogenic, or chemiluminescence detection systems. The use of nonisotopic detection systems will enable laboratories with minimal facilities to identify important regional vectors.

Alkaline Phosphatase↗