Crisis in emergency.
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Emergency Service, Hospital↗
Biomedical subjects
J O'Brien
Publications and source records attributed to J O'Brien.
The effect of minocycline in rat models of inflammatory arthritis: correlation of arthritis suppression with enhanced T cell calcium flux.
Adjuvant and collagen arthritis in the rat are widely accepted T-cell-dependent counterparts of rheumatoid arthritis and were used to examine the antiinflammatory properties of minocycline. Administration of oral minocycline, a semisynthetic tetracycline, significantly decreased (P < 0.01) the incidence of arthritis in both models. In vivo exposure to minocycline also significantly increased the percentage of splenocytes exhibiting a rise in free intracellular calcium concentration ([Ca2+]i) following concanavalin A stimulation (P < 0.05 in adjuvant and P < 0.01 in collagen). This enhancement was mitogen dose-dependent and supported exclusively by extracellular Ca2+. Resting [Ca2+]i levels were unaffected by minocycline and predominantly the CD4+ subset was involved. No changes were observed in weight, IgG antibodies to collagen, synoviocyte release of collagenase and prostaglandin E2, acute inflammation in an air-pouch system, or cell surface expression of activation markers (interleukin-2 and transferrin receptors) by splenocytes or lymph node cells. As a controlled [Ca2+]i rise is a critical event in normal T cell activation, minocycline's antiarthritic profile in vivo may relate to perturbed Ca2+ influx during T cell activation, an alteration that could promote the development of clinical tolerance to otherwise arthritogenic stimuli.
Animals↗
Adventitial remodeling after coronary arterial injury.
BACKGROUND: Intraluminal thrombus formation and medial smooth muscle (SM) cell proliferation are recognized responses of the arterial system to injury. In contrast to these well-characterized processes during vascular repair, changes involving the adventitia have been largely neglected in previous studies. Hence, the goal of this investigation was to assess the response of the adventitia to coronary arterial injury. METHODS AND RESULTS: Adventitial changes in porcine coronary arteries subjected to medial injury were characterized by immunohistochemistry, histochemistry, and microscopic morphometry. The rapid development of a hypercellular response in the adventitia was evident 3 days after balloon-induced medial injury. Cell proliferation, as assessed by proliferating cell nuclear antigen immunostaining, reached the maximum level in the adventitia at 3 days, whereas at 14 and 28 days, the number of replicating cells reverted toward the baseline. The proliferating activity in the adventitia exceeded that seen in the media at all times after injury. To further define the changes in the phenotype of adventitial cells, the expression of three cytoskeletal proteins (vimentin, alpha-SM actin, and desmin) was characterized. Fibroblasts in normal adventitia expressed vimentin but no alpha-SM actin or desmin. After injury, these cells acquired characteristics of myofibroblasts expressing alpha-SM actin, which peaked at 7 and 14 days. Desmin expression was patchy in the adventitia, as opposed to its homogeneous distribution in medial SM cells. The modulation of fibroblast phenotype was transient, inasmuch as alpha-SM actin immunostaining declined at 28 days after injury, when dense, collagen-rich scar was evident within the adventitia. The above-described changes involving hypercellularity of the adventitia, myofibroblast formation, and fibrosis were associated with a significant focal adventitial thickening at 3, 7, 14, and 28 days after injury (P < .01 versus uninjured coronary arteries). CONCLUSIONS: This study demonstrates the involvement of the adventitia in the vascular repair process after medial injury. The hypercellularity of the adventitial layer, proliferation of fibroblasts, and modulation of their phenotype to myofibroblasts are associated with the development of the thickened adventitia. It is postulated that these phenomena affect vascular remodeling and may provide an important insight into the mechanisms of vascular disorders.
Actins↗
Hepatitis C in human immunodeficiency virus-coinfected patients: increased variability in the hypervariable envelope coding domain.
Patients coinfected with the hepatitis C virus (HCV) and the human immunodeficiency virus (HIV) were studied with regard to nucleotide sequence variability in the E2/NS1 first hypervariable region of the HCV genome. The nucleotide variability within individual patients was compared to patients infected only with HCV. The proportion of predicted synonymous and nonsynonymous amino acid changes, and the relationship to putative high-antigenicity sites, were evaluated in the hypervariable envelope domain. Ninety-one clones from 10 patients with HCV/HIV coinfection were sequenced, following polymerase chain reaction (PCR) amplification of the hypervariable region. The control HCV group included 53 clones from 7 patients. Sequence analysis encompassed the region coding for amino acids 384 to 414. Consensus sequences from each patient were used as the internal standard for nonsynonymous amino acid codon variability. Cumulative proportional comparison at each amino acid site revealed increased variability in HCV RNA from patients with HCV/HIV coinfection versus HCV alone (P < .05). The greatest variability was observed at amino acids 386, 397, 400, 402, 405, 407, and 414, with >l0 percent clonal variation at these sites. Jameson-Wolf plots were used to predict putative high-antigenicity domains. Nonsynonymous clonal variation resulted in alteration of putative antigenic sites within the hypervariable region. All clones had at least one high-probability site. Clones with unique predicted antigenic domains were observed more frequently in HIV/HCV coinfected patients, and, independent of viral titer, were consistent with increased sequence variability. These data suggest an accumulation of envelope variants in the HCV/HIV coinfected patients, which could be related to ineffective viral clearance, and may help explain prior reports of interferon (IFN) resistance in this patient group.
Adult↗
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↗
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↗
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↗
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↗
The role of ryanodine receptor isoforms in the structure and function of the vertebrate triad.
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Amino Acid Sequence↗
Urinary incontinence: long term effectiveness of nursing intervention in primary care.
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Exercise Therapy↗
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↗
National measles and rubella vaccination campaign.
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Adolescent↗
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↗
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↗
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↗
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↗
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↗
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↗