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Biomedical subjects

J Clarke

Publications and source records attributed to J Clarke.

At least 181 records · Page 10Linked to original sources
PubMed1995

Pulmonary complications of HIV disease: 10 year retrospective evaluation of yields from bronchoalveolar lavage, 1983-93.

BACKGROUND: Pulmonary disease is a major contributor to morbidity and mortality in patients with HIV infection and AIDS. The aim of this study was to describe bronchoscopic findings and the spectrum of pulmonary pathogens in HIV seropositive patients undergoing investigation of respiratory disease over a 10 year period in a major UK referral centre. METHODS: Recruitment was procedure based with data being captured when bronchoscopy was clinically indicated. Data were evaluated from 580 HIV seropositive patients (559 men, age 13-65 years) over a 10 year period from June 1983 to March 1993. RESULTS: A total of 947 bronchoscopies was performed. The most frequent pulmonary pathogen isolated from bronchoalveolar lavage (BAL) fluid in 44% of all bronchoscopies was Pneumocystis carinii. Of all patients studied, 324 (55%) had at least one cytologically confirmed episode of P carinii pneumonia; this was AIDS defining in 219 (38%) of patients who underwent bronchoscopy. Between 1987 and 1993 the overall diagnostic yield from BAL fluid was 76%; 25% of all bronchoscopies yielded positive microbiological results, the most frequent isolates being Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas spp, and Haemophilus influenzae. Mycobacteria were identified in 8% of patients; M tuberculosis was the most common being identified in 3% of lavage samples and in 4% of patients. No drug-resistant M tuberculosis was found. Viral isolates (mainly cytomegalovirus) were identified in up to 31% of BAL fluid samples. Endobronchial Kaposi's sarcoma was seen in 15% of patients at bronchoscopy. CONCLUSIONS: Of the 1956 newly diagnosed HIV seropositive patients receiving clinical care at St Mary's Hospital over this period, approximately 30% underwent bronchoscopy. Diagnostic rates for P carinii pneumonia, endobronchial Kaposi's sarcoma, and bacterial and mycobacterial infection have remained largely constant since 1989. Bronchoalveolar lavage produces high diagnostic yields generally, and P carinii pneumonia remains a common cause of pulmonary disease in these patients.

Adolescent↗
PubMed1995

Sexual dimorphism in interhemispheric relations: anatomical-behavioral convergence.

An embryogenetic hypothesis states that hemispheric specialization is inversely related to callosal connectivity (Geschwind and Galaburda, 1985). We tested this hypothesis (i) anatomically by relating postmortem planum temporale asymmetry to regional callosal morphology and (ii) behaviorally by relating the right visual field advantage in a lateralized lexical decision task with associative primes to regional callosal morphometry using magnetic resonance imaging (MRI). The postmortem study showed a significant negative correlation between planum temporale asymmetry and the number of small diameter fibers in the isthmus of the corpus callosum, but only for males. The MRI study showed a significant negative correlation between the right visual hemifield advantage for associated words and the cross section size of the isthmus of the corpus callosum, but again only in males. There was no sex difference in either the anatomical asymmetry, the behavioral asymmetry, or the callosal morphology. These convergent results suggest that there is a sexual dimorphism in interhemispheric relations in humans.

Adult↗
PubMed1994

Chemokine-induced fever: intracerebroventricular actions of MIP-1 and MIP-1 alpha in rats.

The central pyrogenic actions in the rat of doublet macrophage inflammatory protein-1 (MIP-1) and MIP-1 alpha were determined by their intracerebroventricular infusion. Doses of 560 pg and 11.2 ng of MIP-1 or 10.0 ng MIP-1 alpha infused into the third cerebral ventricle induced a long lasting fever. However, MIP-1 alpha was much less potent than MIP-1 in terms of intensity and longer latency. Overall, these cytokines are pyrogenic when acting on the walls of the third ventricle; however, a dose 10 times greater than that injected directly into the anterior hypothalamus is required to evoke fever, as based on earlier experiments. Finally, circulating MIP-1 could act centrally by its entry through the choroid plexus into the ventricular system of the brain.

Animals↗
PubMed1994

Isolation of lysozyme-specific T cell clones that discriminate between native and denatured antigen.

Hen egg white lysozyme (HEL)-specific T cell lines and clones were generated from B6 and BDF1 mice. A variety of clonotypes were found among clones generated at an early stage (1 month) whereas fewer clonotypes were detected after several weeks of culture. Furthermore, a bulk line switched from its initial fine peptide specificity pattern (positive for fragment L2--aa. 13-105--and negative for fragment NC--aa. 1-17:Cys 6-Cys 127:120-129) to the opposite pattern (negative for L2 and positive for NC), indicating that in bulk lines, besides selection toward oligo- or monospecificity, clones previously silent can emerge after a period of time. Irrespective of early or late cloning, T cell clones could be isolated from three independent T cell lines from different mouse strains that were stimulated by either native or denatured HEL, but not both. Furthermore, 1 clone of 20 from a B6 line, 3 clones of 25 from a BDF1 line, and 1 T hybridoma clone of 10 of B10.A origin lost their capacity to respond to native HEL, yet continued to respond to reduced, carboxymethylated HEL or cyanogen bromide-cleaved, unreduced HEL. These results suggest that T cells may produce activation signals for efficient processing of native antigen.

Animals↗
PubMed1994

Are tidal breathing indices useful in infant bronchial challenge tests?

Tidal breathing indices have been used to assess histamine-induced airway obstruction in adults and children. The aim of this study was to see whether they could be used to assess histamine challenge in infants. Tidal flow during quiet breathing was measured using a face mask and pneumotachograph and maximum flow at functional residual capacity (VmaxFRC) was measured from partial forced expirations in 18 sleeping, sedated infants who responded to histamine challenge and in 18 nonresponders. The tidal indices calculated were inspiratory and expiratory time (ti and te), tidal peak expiratory flow (PEF), mean tidal expiratory flow rate (VT/te) and the expiratory time constant of the respiratory system (trs). The time to maximal expiration divided by expiratory time (tme/te) and 2 revised forms of this index (tme(a)/te and tme(b)/te) were also calculated. Recordings of tme(a) and tme(b) were taken at 95% of peak tidal expiratory flow, before and after the peak, respectively. In nonresponders, there was an insignificant mean rise in VmaxFRC of 11.8% but no change in any tidal index. In responders, the mean percentage fall in VmaxFRC was 43.3% (range, -31 to -81%); trs fell from 0.61 s to 0.51 s (P < 0.05) and breathing frequency and mean tidal expiratory flow rate increased from 34.0 to 37.5 min-1 (P < 0.01) and from 66.6 to 72.6 mL.s-1 (P < 0.05), respectively, suggesting that infants had adopted a strategy of active expiration in response to bronchial challenge. There was no change either in tme/te or in the revised indices after challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Declining incidence of amputation for arterial disease in Scotland.

OBJECTIVES: To determine time trends and geographical variations in the incidence of major amputation for peripheral arterial disease and whether lower rates of amputation were related to higher rates of arterial reconstruction. DESIGN: Analysis of Scottish hospital discharge data. SETTING: Scotland 1981-1990. MATERIALS: Patients undergoing major amputation or arterial reconstruction for peripheral arterial disease. CHIEF OUTCOME MEASURES: Time trends in age-sex standardised rates of major amputation and arterial reconstruction, and correlation between the rates of these operations by health board. MAIN RESULTS: In Scotland, between 1981 and 1990, the incidence of major amputation fell by 22% (p < 0.001). Inconsistencies were observed within different age-sex groups. In the population under 65 years of age the incidence of amputation fell by 45% (p < 0.001), whereas in those over 65 years the incidence increased by 54% (p < 0.001). Amputation rates fell in men but a paradoxical increase was observed in women. Between 1981 and 1990, rates of arterial reconstruction doubled (p < 0.001), with an increase in all age-sex groups. Rates of amputation and reconstruction varied between health boards of residence, with a positive correlation (r = 0.5) between rates of operations within health board. Therefore areas with higher reconstruction rates tended to have higher amputation rates. CONCLUSIONS: In Scotland, the incidence of amputation has fallen during a period when reconstruction rates have risen greatly. However inconsistencies in time trends by age-sex groups, and the lack of an inverse correlation by health board of residence, suggest that fewer amputations are unlikely to be due solely to an increase in reconstructive surgery.

Adult↗
PubMed1994

Reduction in stereoacuity with age and reduced retinal illuminance.

Stereoacuity has been reported to decrease significantly in the seventh decade of life. Could this decrease be due to a reduction of retinal illuminance in the ageing eye? In this study, we used a more rigorous psychophysical procedure than that used previously, on 35 subjects, aged 21-67 years, to determine if the reported effect of age on stereoacuity could be replicated. We also compared the stereoacuity of 15 healthy young adults under normal and reduced retinal illuminance. A forced-choice algorithm was used to improve the accuracy of measurements. Results suggest that the reduced retinal illuminance resulting from normal ageing is not the cause of the decreased stereoacuity found with ageing.

Adult↗
PubMed1994

Organ preservation without extreme hypothermia using an Oxygen supplemented perfusate.

All methods of organ preservation depend upon hypothermia to depress metabolism during storage. Yet, hypothermia may represent the rate-limiting factor in organ preservation. A new perfusate has been developed which supports organ preservation without extreme hypothermia. The perfusate consists of a complex fluid supplemented with an oxygen carrying perfluorocarbon emulsion, Oxygent (Alliance Pharmaceutical Corp,). The perfusate was used to preserve canine kidney autografts using pulsatile preservation at 32 degrees C and static storage at 25 degrees C. Upon autografting the dogs produced urine within minutes of reperfusion. These results indicate the new perfusate may have significant potential in organ preservation without extreme hypothermia.

Animals↗
PubMed1994

Postmortem organ salvage using an Oxygen supplemented perfusate.

The world-wide shortage of organs for clinical transplantation is caused by the limited existing donor pool of heartbeating cadavers. Attempts to expand into the nonheartbeating cadaver population have been hindered by warm ischemic damage. We evaluated if a new Oxygent (Alliance Pharmaceutical Corp.) supplemented perfusate could be used to salvage canine kidneys postmortem. The kidneys preserved in the Oxygent perfusate could be maintained in situ for time points ranging from one-eight hours postmortem; enough time to declare death and obtain consent for organ donation. In contrast, the control kidneys yielded abnormal histologic findings and impaired flow dynamics. These results suggest that new perfusate may have significant potential to expand the existing organ donor pool.

Adenosine↗
PubMed1993

Local breathing and global unfolding in hydrogen exchange of barnase and its relationship to protein folding pathways.

We have measured the rate constants for exchange of amide protons in 15N-labeled wild-type barnase and a disulfide mutant that is more stable by 2 kcal.mol-1. The relative rate constants for exchange for wild type and mutant should reflect the changes in the equilibrium constants for local or global unfolding. The values for regions whose structure has been shown to be unaffected by the mutation fall into three subsets: those that are essentially unaffected by the mutation and so presumably exchange by local breathing; those where the energies change by close to 2 kcal.mol-1 and so presumably require global unfolding for exchange; and intermediate values that probably reflect a mixture of local and global unfolding in wild-type barnase. Amide protons that require the full change in unfolding energy are predominantly in the beta-sheet, which forms early in folding, but also include two that are involved in tertiary interactions that are known not to be formed until late in the folding pathway. Exchange in the major helix, which is known to form early, is largely unaffected by mutation and so exchanges by local breathing. There is thus no direct relationship between hydrogen-exchange behavior and the protein folding pathway. However, experiments on mutants of varying stability may provide further evidence on the sequence of events in folding.

Amino Acid Sequence↗