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Biomedical subjects

B Cooper

Publications and source records attributed to B Cooper.

At least 37 records · Page 2Linked to original sources

Comparison of serologic assays and PCR for diagnosis of human herpesvirus 8 infection.

A variety of assays for the diagnosis human herpesvirus 8 (HHV-8) infection have been reported. We compared several such assays with a panel of 88 specimens from human immunodeficiency virus (HIV)-infected patients with Kaposi's sarcoma (KS) (current-KS patients; n = 30), HIV-infected patients who later developed KS (later-KS patients; n = 13), HIV-infected patients without KS (no-KS patients; n = 25), and healthy blood donors (n = 20). PCR assays were also performed with purified peripheral blood mononuclear cells (PBMCs) to confirm positive serologic test results. The order of sensitivity of the serologic assays (most to least) in detecting HHV-8 infection in current-KS patients was the mouse monoclonal antibody-enhanced immunofluorescence assay (MIFA) for lytic antigen (97%), the orfK8.1 peptide enzyme immunoassay (EIA) (87%), the orf65 peptide EIA (87%), MIFA for latent antigen (83%), the Advanced Biotechnologies, Inc., EIA (80%), and the orf65 immunoblot assay (80%). Combination of the results of the two peptide EIAs (combined peptide EIAs) increased the sensitivity to 93%. For detection of infection in later-KS patients, the MIFA for lytic antigen (100%), the orfK8.1 peptide EIA (85%), and combined peptide EIAs (92%) were the most sensitive. Smaller percentages of no-KS patients were found to be positive (16 to 56%). Most positive specimens from the current-KS and later-KS groups were positive by multiple assays, while positive specimens from the no-KS group tended to be positive only by a single assay. PCR with PBMCs for portions of the HHV-8 orf65 and gB genes were positive for less than half of current-KS and later-KS patients and even fewer of the no-KS patients. The concordance between serologic assays was high. We propose screening by the combined peptide EIAs. For specimens that test weakly positive, we recommend that MIFA for lytic antigen be done. A positive result with a titer of >/=1:40 would be called HHV-8 positive. A negative or low titer would be called HHV-8 negative. If a population has a high percentage of persons who test positive by the combined peptide EIAs, then a MIFA could be performed with the negative specimens to determine if any positive specimens are being missed. Alternatively, if a population has a low percentage that test positive, then a MIFA could be performed with a subset of the negative specimens for the same reason. As described above, only a titer of >/=1:40 would be considered HHV-8 positive.

Algorithms↗

Two skeletal alpha-tropomyosin transcripts with distinct 3'UTR have different temporal and spatial patterns of expression in the striated muscle lineages of Xenopus laevis.

The Xenopus laevis alpha-tropomyosin (TM) gene, like its vertebrates counterparts, encodes muscle and non-muscle isoforms through two promoters and alternatively spliced exons. In the present study we describe a cDNA clone (XTMalpha7) encoding a skeletal muscle isoform of the gene that differs from the previously described skeletal TM transcript (XTMalpha2) by its 3'UTR sequence. The two skeletal alpha-TM encoding mRNAs are generated through distinct 3'end processing using different polyA signals and distinct patterns of exon splicing. Using RNAse protection and RNA in situ hybridization, we have analysed the developmental and spatial expression of the two transcripts. Both are expressed in the embryo, but XTMalpha7 is by far the most prevalent of the two. In contrast, only XTMalpha2 is expressed in adult striated muscle tissues. In the embryo, the spatial expression of XTMalpha7 is restricted to the somites whereas XTMalpha2 is expressed in both somites and embryonic heart.

3' Untranslated Regions↗

Preliminary research on plasma oxytocin in normal cycling women: investigating emotion and interpersonal distress.

The neurohormone oxytocin is responsible for initiating childbirth and the let-down reflex in lactating women and is released during sexual orgasm. Oxytocin has been thought of as an affiliation hormone because research on nonhuman mammals has demonstrated that it plays a key role in the initiation of maternal behavior and the formation of adult pair bonds. It has been speculated that social stimuli may induce oxytocin release and that oxytocin may make positive social contact more rewarding. Data are presented from an initial study to examine change in plasma oxytocin in response to a standard imagery task that elicits emotion related to attachment. Twenty-five normal cycling, healthy women underwent imagery tasks and completed questionnaires on attachment and interpersonal problems. Blood draws (5 ml) were bone via an indwelling catheter before, during, and after three interventions (massage, positive emotion, and negative emotion) and to establish baselines. Overall, the data showed a tendency for oxytocin levels to be elevated in response to relaxation massage and decreased in response to sad emotion. There were individual differences in response to the interventions. Those who showed evidence of increased oxytocin levels for positive emotion and massage and who maintained oxytocin levels during negative emotion were less likely to report interpersonal problems associated with intrusiveness. Maintaining oxytocin levels during sadness was also correlated with lower anxiety in close relationships. Women who were in a couple relationship had greater increases in oxytocin in response to positive emotion. In contrast, higher basal levels of oxytocin were associated with greater interpersonal distress. These data suggest that peripheral secretion of oxytocin in response to emotional stimuli is associated with the individual's interpersonal characteristics.

Adult↗

Trauma modifies strength and composition of retrodiscal tissues of the goat temporomandibular joint.

OBJECTIVES: Temporomandibular pain is often accompanied by pathologic changes to joint retrodiscal tissues. The substantial representation of females in this condition has encouraged hypotheses which link genetic or hormonally induced abnormalities in tissue composition (type III collagen, type I collagen, type III/type I ratio) to the development of temporomandibular disorders. As this condition is often associated with a history of orofacial trauma, we investigated the functional impact of retrodiscal trauma on the composition and biomechanics of retrodiscal tissues. DESIGN AND METHODS: Retrodiscal tissue of female goats received trauma or sham trauma. Following a healing period of 30 days, the tissues were pulled to failure on an extensometer. OUTCOME MEASURES: Assessments were made of tissue biomechanical properties (failure force, elastic stiffness, strain distribution). Tissue fragments were assayed for collagens I and III. RESULTS: Thirty days after surgical section of retrodiscal tissues, the tissue had reformed, but the composition and biomechanics were substantially changed. Healed tissue manifested less than half the strength of normal tissue (P = 0.02). In addition, the development of tissue strain shifted from a relatively even distribution to a confined region near the retrodiscal-discal attachment zone. It appeared that a large increase in the expression of type III collagen (179.6%; P = 0.038) and the ratio of type III/type I collagen (180.9%; P = 0.011) accounted for these functional changes. CONCLUSIONS: We suggest that shifts in collagen expression following injury create shifts in strain development which focus tissue stresses near the interface of the disc and retrodiscal tissue, and that this shift dramatically weakens the tissue and increases the probability of re-injury, inflammation and pain.

Animals↗

Independent effects of Apo E phenotype and plasma triglyceride on lipoprotein particle sizes in the fasting and postprandial states.

LDL particle sizes and Apo E phenotypes were determined in 212 subjects of whom 51 had angina. LDL diameter was significantly less in subjects with an epsilon2 allele (24.76+/-0.08 vs 24.94+/-0.02 nm, P=0.02), and this was evident for both E2/E3 (24.77+/-0.09 nm) and E2/E4 (24.69+/-0.08 nm) phenotypes. Although there was a negative relation between LDL diameter and plasma triglyceride, the effect of apo E2 was still evident with adjustment for triglyceride. In multiple regression analysis, the significant determinants of LDL diameter were gender (with females having larger particles than males), body mass index, and the presence (or absence) of E2. HDL particle sizes and compositions were determined on fasting samples and, additionally, 5 and 8 hours after a fat-rich meal for 48 coronary heart disease cases and 49 control subjects. Fasting HDL particle sizes were not related to the presence of E2 but were significantly smaller for subjects possessing an epsilon4 allele (8. 09+/-0.08 vs 8.39+/-0.05 nm, P=0.003) and were negatively related to plasma triglyceride. However, the effect of E4 persisted after adjustment for triglyceride. In a multiple regression analysis, the only significant determinant of fasting HDL diameter was the presence (or absence) of E4 with fasting plasma triglyceride just failing to reach significance (P=0.06). There was a postprandial increase in HDL diameter that was less marked in subjects with coronary heart disease. The postprandial increase in HDL diameter was of sufficient magnitude to result in size reclassification of HDL particles. The influence of E4 was also evident at both postprandial time points. Compositional analysis demonstrated that the increase in HDL diameters postprandially could be attributed to triglyceride enrichment, with an accompanying fall in cholesterol ester content. Phospholipid changes postprandially were biphasic with an initial fall followed by a rise in concentration. The increase in triglyceride content was significantly less in those subjects with angina despite an equivalent rise in plasma triglyceride. The present study demonstrates significant, but different, effects of variation in apo E phenotype on the particle sizes of both HDL and LDL. Such effects were still evident with adjustment for differences in plasma triglyceride and suggests that variation in apo E phenotype exerts effects on lipoprotein particle sizes by mechanisms additional to those dependent on change in plasma triglyceride.

Alleles↗

Application of the Person-Environment-Occupation Model: a practical tool.

Occupational therapy focuses on complex dynamic relationships between people, occupations and environments. Therapists must clearly communicate their practices and how their practice influences outcomes. This paper explores applications of the Person-Environment-Occupation Model (Law et al., 1996) in occupational therapy practice, and delineates how this particular model helps therapists to conceptualize, plan, communicate and evaluate occupational performance interventions. Three case studies illustrate how the model can be used by occupational therapists to systematically approach analysis of occupational performance issues while considering the complexities of human functioning and experience. The ways in which the model facilitates communication within and outside occupational therapy are explained. The Person-Environment-Occupation Model is offered as a tool for therapists to use in client(s)-therapist alliances to enable clients to successfully engage in meaningful occupations in chosen environments.

Aged↗

Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group.

PURPOSE: To assess the antitumor activity, safety, and hormone-suppressive effects of the irreversible aromatase inactivator, exemestane (Aromasin, Pharmacia & Upjohn, Kalamazoo, MI), administered as third-line hormone therapy to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate. PATIENTS AND METHODS: Exemestane was administered at a dose of 25 mg/d orally until patients experienced disease progression. The efficacy and safety of exemestane were clinically and radiographically evaluated. The impact of exemestane treatment on tumor-related signs and symptoms was assessed. The effect of exemestane on serum levels of estrogens and other steroidal hormones was determined. RESULTS: Ninety-one patients were treated. There were four complete responses (CR) and eight partial responses (PR), for an objective response rate of 13% in the entire treated population. The overall success rate (CR, PR, or stable disease [SD] >/= 24 weeks) was 30%. The median duration of response and overall success was 9 months and 8 months, respectively. Most patients with CR/PR (83%; 10 of 12 patients) and SD >/= 24 weeks (80%; 12 of 15 patients) had improved or stable tumor-related signs and symptoms. Mean levels of circulating estrone (E(1)), estradiol (E(2)), and estrone sulfate decreased to 11%, 22%, and 13% of baseline levels, respectively (at week 8 or 16 of treatment). One half of the patients had undetectable E(1) and E(2) levels during treatment, including at the time of disease progression. Mild nausea (20% of patients) and hot flashes (20%) were the most common drug-related adverse events and were generally grade 1. CONCLUSION: Exemestane is an active and well-tolerated third-line hormonal therapy that represents a new treatment option for postmenopausal patients with advanced breast cancer that has become refractory to standard first- and second-line hormonal therapies.

Adult↗

Differential expression of two skeletal muscle beta-tropomyosin mRNAs during Xenopus laevis development.

A cDNA clone for a Xenopus laevis skeletal muscle beta-tropomyosin (beta-TMad) isoform was isolated from an adult skeletal muscle cDNA library. Sequence analysis revealed that this clone corresponded to a second beta-tropomyosin mRNA distinct from the one that was previously characterized (beta-TMemb). The two skeletal beta-TM mRNAs originate from distinct genes and are differentially expressed during development. Beta-TMemb mRNA is expressed only in the somites of the early embryo while beta-TMad mRNA is expressed in pre-metamorphic tadpoles and adult skeletal muscles. We have isolated the promoter region of the beta-TMemb gene and shown that a DNA construct containing 2.9 kb of promoter region is properly expressed after injection in the embryo.

Animals↗

Effective surgical treatment of cubital tunnel syndrome based on provocative clinical testing without electrodiagnostics.

This study evaluated the effectiveness of identifying surgically correctable ulnar nerve compression at the elbow based on provocative clinical testing alone in patients with cubital tunnel syndrome after failure of conservative treatment. Twenty-four patients were included in the study (mean age, 60 years). Three patients underwent bilateral procedures. Patients complaining of symptoms in the distribution of the ulnar nerve were tested by elicitation of Tinel's sign and combined flexion and pressure testing at the elbow and wrist. Two-point discrimination was determined. After a failed 6-week trial of conservative therapy patients underwent anterior submuscular transposition of the ulnar nerve with carpal tunnel release. Postoperatively, the change in two-point discrimination as measured at 6 months was significantly improved, with a mean improvement per digital nerve of 2.52 mm (p<0.001). Mean time to relief was 7.2 weeks. Complications included one hematoma and one seroma. A total of 26 of the 27 limbs chosen for surgical treatment by provocative clinical testing alone experienced relief of symptoms with anterior submuscular transposition of the ulnar nerve and carpal tunnel release. This study demonstrates the effectiveness of surgical therapy in patients with lesions identified by clinical examination without electrodiagnostic testing.

Cubital Tunnel Syndrome↗

Evolution, partnerships and cooperation.

In an evolutionary game theoretic setting, players are allowed to choose not only their strategies for a particular interaction, but also to some extent with whom they will play. A stability concept is presented and examined which allows agents to endogenously construct fixed partnerships. A strategy-matching type is said to be recoverable if a population in which it is used by all players is both internally and externally stable to random mutations. Such a strategy-matching type always exists and maximises social efficiency in the population. Some examples are considered in the light of this concept. The ability to form fixed partnerships enables players to coordinate on efficient outcomes. In particular, cooperation is achieved in the Prisoners' Dilemma without recourse to repetition or rigid spatial restriction.

Animals↗

Structural selectivity and molecular nature of L-glutamate transport in cultured human fibroblasts.

Uptake of L-[3H]glutamate by monolayers of fibroblasts cultured from human embryonic skin has been studied in the presence of several nonradioactive structural analogs of glutamate and aspartate. Results have suggested that the structural specificites of glutamate transporters in cultured human fibroblasts are similar to those of glutamate transporters in the mammalian brain. Only subtle differences have been detected: in the mammalian cerebral cortex, enantiomers of threo-3-hydroxyaspartate are almost equipotent as inhibitors of L-[3H]glutamate uptake while, in human fibroblasts, the D-isomer has been found to be an order of magnitude less potent than the corresponding L-isomer. Kinetic analysis of a model in which substrates are recognized by the glutamate transporter binding site(s) as both alpha- and beta-amino acids indicated that such a mechanism cannot explain the apparent negative cooperativity characterizing the effects of D- and L-aspartate. Molecular modeling has been used to estimate the optimum conformation of L-glutamate as it interacts with the transporter(s). Flow cytometry has indicated that all fibroblasts in culture express at least moderate levels of four glutamate transporters cloned from human brain. Small subpopulations (< 3%) of cells, however, were strongly labeled with antibodies against EAAT1 (GLAST) and EAAT2 (GLT-1) transporters. We conclude that these two transporters--known to be strongly expressed in brain tissue--can be principally responsible for the "high affinity" transport of glutamate also in nonneural cells.

ATP-Binding Cassette Transporters↗

Dementia care needs in an area population: case register data and morbidity survey estimates.

OBJECTIVE: To compare case register data on the frequency and distribution of known dementia cases in a metropolitan area population with expected total numbers computed from a national disability survey. METHOD: Known cases were enumerated by a cross-sectional census of the Camberwell Dementia Register. Expected total numbers were calculated using the Cognitive Disability (CD) Planning Model, based on the OPCS national survey of disability, 1985-86. RESULTS: Cases ascertained by the Dementia Register census comprised one-fifth of expected total prevalence. The proportion of such cases was higher for persons in long-stay care (1 in 3) than for those in private households (1 in 7). According to the CD Planning Model, cases known to specialist agencies were on average no more severely disabled and dependent than those who were unknown. In terms of absolute numbers, the district nursing and home help services appeared to be the most important untapped sources of case detection, but other research indicates that general practice contacts (not included in the planning model) may be at least equally important. CONCLUSIONS: At any given time, a high proportion of dementia cases, whether in long-stay care or in the community, will be outside the purview of specialist services. Primary care agencies are a major potential source, and a systematic health screening of persons aged over 75 years could be used to realize this potential.

Aged↗

Relationships between protein C, protein S, von Willebrand factor and euglobulin lysis time and cardiovascular risk factors in subjects with and without coronary heart disease.

Measures of fibrinolytic and thrombotic function have been examined in 55 subjects with recently identified coronary heart disease, and age and sex matched control subjects. Measurements were particularly directed at factors and processes which could be affected by changes in endothelial function and included the euglobulin lysis time as well as plasma levels of von Willebrand factor (vWF). Plasma levels of protein S and protein C were also measured. Measurements were made before and after a period of 10-min veno-occlusion combined with rhythmic hand exercise. In addition anthropometric, haemodynamic and biochemical measurements (plasma lipids and apolipoproteins, glucose and insulin) were obtained and correlated with the haematological parameters. Protein S and vWF levels were significantly higher, both before and after veno-occlusive exercise, in subjects with CHD than in the asymptomatic controls. Euglobulin lysis times were not significantly different but only shortened on veno-occlusive exercise in those without CHD. Protein S levels were significantly correlated with systolic blood pressure, plasma total cholesterol, plasma triglyceride, plasma phospholipid, plasma fasting glucose and both apolipoprotein A1 and B levels. vWF levels were not significantly related to any of the other variables. Subjects whose pre-exercise euglobulin lysis times exceeded 6 h had significantly higher BMI, plasma total cholesterol, triglyceride, phospholipid, insulin, glucose and apoB concentrations and lower HDL cholesterol than those with lysis in less than 6 h. The findings from this study are consistent with a role for endothelial dysfunction in the production of atherosclerotic vascular disease and may indicate additional, non-haemodynamic, mechanisms for such an association. In addition, the relationship between elevated levels of protein S and CHD does not appear to depend on the demonstrated associations between protein S and a number of other cardiovascular risk factors.

Aged↗