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Biomedical subjects

J O'Brien

Publications and source records attributed to J O'Brien.

At least 145 records · Page 8Linked to original sources
PubMed1996

The relationship between plasma potassium, muscle membrane excitability and force following quadriceps fatigue.

To examine the simultaneous changes in plasma [K+], muscle excitability and force during fatigue, ten male adults (mean age = 22 +/- 0.5 years) held an isometric contraction of their right quadriceps muscle at an intensity of 30% maximum voluntary contraction (MVC) for 3 min. Femoral venous and brachial arterial [K+] were determined from serial samples drawn before, during, and for 15 min following the 3-min contraction. Each blood sample was synchronized with a maximal stimulation of the right femoral nerve to evoke a twitch and compound muscle action potential (M-wave). Immediately post-exercise, twitch torque was only 42% of baseline and femoral venous plasma [K+] had increased significantly from 4.02 +/- 0.08 mmol/l to 5.9 +/- 0.22 mmol/l. Femoral venous plasma lactate rose to a peak level of 10.0 +/- 0.8 mmol/l at 1 min post exercise. The recovery of the twitch torque was exponentially related to the recovery of femoral venous plasma [K+] (r2 = 0.93, P < 0.01). There was no evidence for any loss of muscle membrane excitability during the period of increased extracellular [K+], in fact, the M-waves tended to be potentiated in the early phases of the recovery period. These results suggest that muscle membrane excitability is maintained in spite of increased extracellular [K+] following fatigue induced by a sustained submaximal quadriceps contraction. However, the strong relationship between twitch torque and femoral venous plasma [K+] suggests that K+ may be exerting its effect distal to surface membrane action potential propagation, most likely in the T-tubular region.

Adult↗
PubMed1996

Connexin 35: a gap-junctional protein expressed preferentially in the skate retina.

We have used low stringency hybridization to clone a novel connexin from a skate retinal cDNA library. A rat connexin 32 clone was used to isolate a single partial clone that was subsequently used to isolate seven more overlapping clones of the same cDNA. Two clones containing the entire open reading frame have a consensus sequence of 1456 bp and predict a protein of 302 amino acids length and molecular mass of 35,044 daltons, referred to as connexin 35 or Cx35. Southern blot analysis suggests that the cloned sequence lies in a single gene with one intron. Polymerase chain reaction amplification from genomic DNA and partial sequencing of this intron showed that it was approximately 950 bp in length, and located within the coding region 71 bp after the translation start site. Hydropathy analysis of the predicted protein and alignments with previously cloned connexins indicate that Cx35 has a long cytoplasmic loop and a relatively short carboxyl terminal tail. Multiple sequence alignments show that Cx35 has similarities to both alpha and beta groups of connexins and suggests that its origins may be near the divergence point for the two groups. Consensus sequences consistent with sites for phosphorylation by protein kinase C and by cAMP - or cGMP -dependent protein kinase were identified. Two transcripts were detected in Northern blot analysis: a 1.95-kb primary transcript and a 4.6-kb minor transcript. In RNA samples from 10 tissues, transcripts were detected only in the retina.

Amino Acid Sequence↗
PubMed1996

A magnetic resonance imaging study of white matter lesions in depression and Alzheimer's disease.

BACKGROUND: White matter changes, as revealed by magnetic resonance imaging (MRI), may occur in depression and Alzheimer's disease. METHOD: T2-weighted MRI scans were performed in 39 control subjects, 61 subjects with NINCDS/ADRDA Alzheimer's disease and 60 subjects with DSM-III-R major depression. Deep white matter lesions (DWML) and periventricular lesions (PVL) were rated on a standard 0-3 scale by two radiologists blind to clinical diagnosis. RESULTS: After controlling for differences in vascular risk factors and current blood pressure, DWML were significantly more common in depressed subjects and PVL in Alzheimer's disease subjects compared to controls. DWML were most common in those presenting in late life with their first ever depression and 50% of such subjects had severe (grade 3) DWML. CONCLUSION: An association between DWML and depression and PVL and Alzheimer's disease is supported. The increase with DWML that occurs with ageing may predispose some elderly subjects to depression.

Aged↗
PubMed1996

Effects of Ca2+ on oxidative phosphorylation in mitochondria from the thermogenic organ of marlin.

Mitochondria from the muscle-derived thermogenic (heater) organ and oxidative red muscle of the blue marlin (Makaira nigricans) were studied in order to evaluate aspects of the mechanism of thermogenesis in heater tissue. We investigated whether short-term Ca(2+)-induced uncoupling of mitochondria contributes to the thermogenic cycle of the heater organ by enhancing the respiration rate. Specific electrodes were used to obtain simultaneous measurements of oxygen consumption and Ca2+ fluxes on isolated mitochondria, and the effects of various concentrations of Ca2+ on respiration rates and the ADP phosphorylated/atomic oxygen consumed (P/O) ratio were examined. Addition of Ca2+ in excess of 10 mumol l-1 to respiring heater organ or red muscle mitochondria partially inhibited state 3 respiration and reduced the P/O ratio, indicating that the mitochondria were partially uncoupled. These effects were blocked by 2 mumol l-1 Ruthenium Red. In heater organ mitochondria, state 3 respiration rate and the P/O ratio were not significantly reduced by 1 mumol l-1 free Ca2+, a concentration likely to be near the maximum achieved in a stimulated cell. This indicates that transient increases in cytosolic Ca2+ concentration may not significantly reduce the P/O ratio of heater organ mitochondria. The activity of 2-oxoglutarate dehydrogenase in heater organ mitochondria was stimulated by approximately 15% by Ca2+ concentrations between 0.2 and 1 mumol l-1. These results suggest that heater organ mitochondria are able to maintain a normal P/O ratio and should maintain ATP output during transient increases in Ca2+ concentration, supporting a model in which an ATP-consuming process drives thermogenesis. Activation of mitochondrial dehydrogenases by low levels of Ca2+ may also enhance respiration and contribute to thermogenesis.

Adenosine Diphosphate↗
PubMed1995

Distractibility in schizophrenia.

This study examined the effects of neuroleptic medication on the allocation of attentional resources to distracting stimuli in patients with schizophrenia. Twenty-five patients were tested twice (medication-free and after medication stabilization) on the Identical Pairs versions of the Continuous Performance Test under both distraction and no-distraction conditions. Sixteen patients were chronically ill adults and nine patients were young neuroleptic-native patients in the early stages of illness. Results indicated that neuroleptic treatment did not improve distractibility for either group and that both groups were comparably distractible. These findings suggest that medication does not improve the misallocation of attention to distracting stimuli in patients with schizophrenia.

Acute Disease↗
PubMed1995

Evaluation of a community arthritis program in Australia: dissemination of a developed program.

OBJECTIVE: To evaluate the effectiveness of a community-based arthritis education program conducted in a number of locations throughout the Sydney, Australia, metropolitan area. METHODS: The program, based on earlier work, comprised 6 weekly sessions of 2.5 hours' duration. The study sample included 175 men and women with different types of arthritis, divided into intervention (n = 104) and control (n = 71) groups. Five outcome measures were selected to evaluate effectiveness of the program: pain perception, knowledge level, self-efficacy, disability index, and self-management behavior. RESULTS: The results indicated that the program was effective in increasing knowledge level (F[1,222] = 10.3, P = 0.001 at 6 weeks; F[1,108] = 7.8, P = 0.006 at 6 months), and a statistically significant difference was found in disability satisfaction 6 months after intervention (F[1,98] = 5.9, P = 0.01], but no statistically significant difference was found in pain perception, self-efficacy, and disability index. CONCLUSION: This research supports some of the successful outcomes which follow an arthritis education program: increased knowledge level and increased disability satisfaction.

Aged↗
PubMed1995

Strange-male-induced pregnancy disruption in mice: reduction of vulnerability by 17 beta-estradiol antibodies.

It is well-established that novel males can disrupt early pregnancy in house mice. Inseminated female C57BL mice were either left undisturbed or each exposed indirectly to a novel HS male through a wire-mesh grid during days 1-6 of pregnancy. Varied dosages of antibodies to 17 beta-estradiol were administered to females exposed to males. Vehicle-treated females exposed to novel males showed fewer litters than did nonexposed controls. Male-exposed females given 1 ml daily of the antibody showed rates of pregnancy comparable to those observed in controls. These data suggest that estrogen levels might play a role in strange-male-induced pregnancy disruptions, converging with evidence implicating estrogens in stress-induced pregnancy blocks.

Animals↗
PubMed1995

Alteration in the frequency, severity and duration of chemotherapy-induced mucositis in hamsters by interleukin-11.

Ninety-five young, male Golden Syrian hamsters were randomly divided into five equally sized groups. One group served as a placebo control while the animals in the others received one of four doses of interleukin-eleven (IL-11) twice daily given by subcutaneous injection beginning on the first day of chemotherapy (day 0) and continuing to day 14. Mucositis was induced with 5-fluorouracil using a standard regimen of 60 mg/kg, intraperitoneally on days 0 and 2 followed by superficial mucosal irritation on day 4. Animals were evaluated daily beginning on day 6. Mucositis was assessed using a standardised technique in which randomly numbered daily mucosal photographs were scored by three blinded independent observers at the conclusion of the experiment. IL-11 favourably affected the frequency, severity and duration of mucositis. This phenomenon appeared to be dose dependent. Hamsters receiving 30 and 100 micrograms per day of IL-11 demonstrated significantly (P < 0.05) lower mucositis scores than did either the control or animals receiving 3 or 10 micrograms per day, although the latter had marginal beneficial effects. Additionally, survival was significantly better for hamsters receiving higher doses of IL-11 (85%) compared to the placebo control (46%). IL-11 administration also favourably affected weight loss. While stimulation of platelet production was noted in animals receiving IL-11, a lack of difference in bone marrow cellularity between test and control animals suggests that the mechanism by which IL-11 modifies mucositis is mediated at the epithelial or connective tissue level rather than through the marrow. The kinetics of IL-11 alteration of mucositis induction supports such a hypothesis. Further investigation is currently underway to establish a definitive mechanism by which IL-11 protects the oral mucosa.

Animals↗
PubMed1995

Physiological differences between the alpha and beta ryanodine receptors of fish skeletal muscle.

Two isoforms of the sarcoplasmic reticulum Ca2+ release channel (ryanodine receptor or RYR) are expressed together in the skeletal muscles of most vertebrates. We have studied physiological properties of the two isoforms (alpha and beta) by comparing SR preparations from specialized fish muscles that express the alpha isoform alone to preparations from muscles containing both alpha and beta. Regulation of channel activity was assessed through [3H]ryanodine binding and reconstitution into planar lipid bilayers. Distinct differences were observed in the calcium-activation and -inactivation properties of the two isoforms. The fish alpha isoform, expressed alone in extraocular muscles, closely resembled the rabbit skeletal muscle RYR. Maximum [3H]ryanodine binding and maximum open probability (Po) of the alpha RYR were achieved from 1 to 10 microM free Ca2+. Millimolar Ca2+ reduced [3H]ryanodine binding and Po close to zero. The beta isoform more closely resembled the fish cardiac RYR in Ca2+ activation of [3H]ryanodine binding. The most prominent difference of the beta and cardiac isoforms from the alpha isoform was the lack of inactivation of [3H]ryanodine binding and Po by millimolar free Ca2+. Differences in activation of [3H]ryanodine binding by adenine nucleotides and inhibition by Mg2+ suggest that the beta and cardiac RYRs are not identical, however. [3H]ryanodine binding by the alpha RYR was selectively inhibited by 100 microM tetracaine, whereas cardiac and beta RYRs were much less affected. Tetracaine can thus be used to separate the properties of the alpha and beta RYRs in preparations in which both are present. The distinct physiological properties of the alpha and beta RYRs that are present together in most vertebrate muscles support models of EC coupling incorporating both directly coupled and Ca(2+)-coupled channels within a single triad junction.

Animals↗
PubMed1995

Response of recent human immunodeficiency virus seroconverters to the pneumococcal polysaccharide vaccine and Haemophilus influenzae type b conjugate vaccine.

Antibody responses in recent human immunodeficiency virus (HIV) seroconverters to 2 vaccines were studied. Twenty patients infected with HIV for < 18 months and 15 HIV-seronegative controls were vaccinated with the 23-valent pure polysaccharide pneumococcal vaccine and the Haemophilus influenzae type b (Hib) capsular polysaccharide diphtheria CRM197 protein toxoid conjugate vaccine in separate arms. Despite increased levels of total serum IgG, recent seroconverters and controls showed similar specific IgG responses for 6 of 7 antigens. Baseline levels were equivalent in both groups, as were peak levels of IgG at 1 month to conjugated polysaccharide (Hib), delayed-type hypersensitivity, and pneumococcal capsular serotypes 4, 6B, 12F, and 14. At 6 months, IgG levels were similar for 4 of 7 antigens. Antibody responses to pure pneumococcal capsular polysaccharides and to a protein recall antigen were most often similar among recent seroconverters and seronegative controls. Both total levels and fold-rises of IgG to the Hib conjugate were similar in the 2 groups. Immunization of HIV-infected patients soon after seroconversion rather than later appears to improve antibody responses.

Adult↗
PubMed1995

Antibody class and subclass responses to pneumococcal polysaccharides following immunization of human immunodeficiency virus-infected patients.

Antibodies of the IgM class and IgG2 and IgA2 subclasses are prominent in responses to pneumococcal polysaccharides (PPS) but may be decreased in human immunodeficiency virus (HIV)-infected patients, among whom invasive pneumococcal disease is common. After immunization of HIV-infected and -seronegative subjects with pneumococcal vaccine, the number of PPS-specific antibody-secreting cells (ASC) producing IgM was significantly lower among HIV-infected subjects, whereas PPS-specific IgG and IgA ASC were more comparable. The subclass distribution of PPS-specific IgG2-producing (approximately 80%) and IgA2-producing (approximately 50%) ASC and antibodies in serum were similar. However, before immunization, the proportions of PPS-specific IgG2 for both serotypes 8 and 14 in baseline sera from HIV-infected patients were significantly decreased compared with controls. Thus, the response to PPS among HIV-infected patients may be characterized by lower levels of specific IgG2 before immunization and prominent defects in IgM responses soon after stimulation.

Adult↗
PubMed1995

Femoral deep vein thrombosis associated with central venous catheterization: results from a prospective, randomized trial.

OBJECTIVE: To determine the frequency of central venous catheter-induced deep vein thrombosis of the femoral vein. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary care center. PATIENTS: Forty-five patients in a medical-surgical intensive care unit who required central venous catheterization. INTERVENTIONS: Patients were randomized to receive central venous catheterization in either upper (subclavian or internal jugular veins) or lower (femoral vein) catheterization sites. Lower extremity duplex ultrasound examinations were performed before central venous catheter placement, after removal of the catheter, and 7 days after catheter removal. Ultrasound examinations were reported as positive, nondiagnostic, or negative for deep vein thrombosis. MEASUREMENTS AND MAIN RESULTS: Of the 21 patients randomized to upper access sites, none developed positive or nondiagnostic duplex ultrasound examinations. Six (25%) of 24 patients randomized to the femoral access site developed lower extremity deep vein thrombosis (p = .02). In addition, seven (29%) patients randomized to the lower access site sustained non-diagnostic ultrasound examinations. A total of 13 (54%) of 24 patients from the lower access group developed abnormal ultrasound examinations (p < .001). Age, duration of catheterization, coagulation profile, deep vein thrombosis prophylaxis, and Acute Physiology and Chronic Health Evaluation II scores were similar between the upper and lower access groups. CONCLUSIONS: Based on the data from this study, we concluded that femoral vein catheterization is associated with a 25% frequency of lower extremity deep vein thrombosis compared with similar patients receiving subclavian or internal jugular vein catheters. The femoral vein remains an important emergency venous access route. Physicians inserting femoral vein catheters should be aware of the risk of lower extremity deep vein thrombosis and should consider performing lower extremity duplex ultrasound examinations on removal of femoral vein catheters.

Catheterization, Central Venous↗
PubMed1995

Outpatients revisited: subjective views and clinical decisions in the management of general surgical outpatients in south west England.

STUDY OBJECTIVE: To assess the scope for reducing unnecessary outpatient reattendances, using a benchmark an acute specialty at a site recognised to have an especially low ratio of repeat to new attendances. DESIGN: This was a survey of the re-attendance workload at general surgery outpatient clinics over a three month period. Patient re-booking and discharge rates for different grades of staff; clinicians' perception of the ability of the GP to have managed the patient; perception of the value of individual re-attendances; reason given for discharging/re-booking; and outcome of attendance for patients in relation to diagnostic category were determined. SETTING: General surgery outpatients clinics with re-attendance rates that were 50% below average, in Taunton and Somerset Hospital, a non-teaching district general hospital. PATIENTS: Altogether 454 patients who made 470 second or subsequent visits (re-attendances) within the same episode of outpatient care. MAIN RESULTS: Thirty eight percent (178/470) of visits were perceived as manageable by the GP, 45% (79, 17% of total re-attendances) of which were also thought to have been of marginal or little value. A substantial group of patients was being followed up largely for reasons of convention and traditional policy. Re-booking rates were higher among junior staff. Subjective views of the value of attendance at the hospital outpatient clinic and the ability of the GP to have seen the patient varied systematically between consultants and junior staff. Judgements varied to some extent according to the diagnostic group. CONCLUSION: The numbers of patients being followed up equivocally at most general surgical outpatient departments will be 50% more an average than those in this benchmark department. A department seeing 2000 new patients per annum will have 3600 reattendances, 25.5% (918) of which may be avoidable on the basis of these results. A variety of approaches can be used to increase the proportion of patients seen appropriately by GPs. In some cases this might be achieved without the intensive commitment required to plan and develop shared care protocols or new formal discharge guidelines, but by encouraging GPs to manage some patients, increasing of hospital clinicians' access to knowledge of local general practices, and internal clinic review of 'routine' follow up policies as shown in this study. This type of review of outpatient practice can also help prioritise conditions likely to repay the effort of developing and implementing clinical management guidelines and local protocols.

Delivery of Health Care↗
PubMed1995

Characterization of the alloreactivity and anti-leukemia reactivity of cord blood mononuclear cells.

It has been suggested that cord blood T cells may be less able to mediate GVHD than marrow-derived T cells due to their naive status. A decreased potential for GVHD may be advantageous for allogeneic transplant, but this benefit might be counteracted by loss of the GVHD associated graft-versus-leukemia (GVL) effect. The GVL potential of cord blood could be doubly compromised since cord blood NK cell activity is also decreased. To assess these issues we have performed extensive comparative functional and immunophenotypic evaluations of cord and adult mononuclear cells. We found a somewhat reduced alloproliferative, allostimulatory and allocytolytic capacity of cord blood mononuclear cells in bulk assays but not by limiting dilution assays. Immunophenotyping revealed no significant differences in the proportion of major lymphocyte subsets with the exception of the previously recognized predominance of CD45RA+ cells in both CD4 and CD8 cord blood T cells. Cord blood T cells expressed normal percentages of the cellular adhesion molecules, CD11a, CD18 and LFA-3; however, the antigen density of each of these molecules was less than that found on adult T cells. Fewer resting cord blood T cells expressed CD54, the ligand for LFA-1. Cord blood B cells and monocytes expressed normal levels of HLA-class I and HLA class II DR, DP and DQ antigens, suggesting that the decreased expression of cellular adhesion molecules or their receptors rather than a decrease in expression of HLA might have contributed to the lower alloreactivity of cord blood. Although the percentages of NK cells and NK cell subsets in adult and cord blood were similar our data confirmed that cord blood has very low NK lytic activity. In contrast, LAK activity was much more readily induced in cord blood compared with adult PBMC, a finding which could be explained in part by a higher frequency of LAK precursors and a more rapid expansion of NK cells in response to culture with medium containing of NK cells in response to culture with medium containing IL-2. Cord blood LAK cells were readily able to lyse fresh leukemia targets from patients with ALL, AML and CML. The data indicate that although the alloreactive potential of cord blood cells may be somewhat decreased, it is not absent and must be considered a factor in cord blood transplants. LAKp with the potential to lyse leukemia are present in increased numbers in cord blood and might contribute to the GVL effect of a cord blood transplant.

Adult↗