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Biomedical subjects

G Harrison

Publications and source records attributed to G Harrison.

At least 145 records · Page 8Linked to original sources

Hyperoxia alters effect of calcium on rat alveolar macrophage superoxide production.

The effect of hyperoxia on the Ca2+ dependence of stimulated superoxide anion radical (O2-.) production (the respiratory burst) of rat alveolar macrophages was investigated. Enhancement of the concanavalin A (con A)-stimulated respiratory burst by extracellular Ca2+ was suppressed by O2 exposure. Similarly, the inhibitory effect of verapamil on the con A-stimulated respiratory burst was reduced by O2 exposure. O2 exposure also inhibited con A stimulation that was independent of Ca2+ entry. Exposure to O2 also caused a decline in O2-. production stimulated by either A23187 or phorbol myristate acetate (PMA). With A23187 stimulation, extracellular Ca2+ was essential for either air-exposed (control) or O2-exposed cells. With PMA, stimulation was independent of extracellular Ca2+ for either air or O2-exposed macrophages and verapamil did not inhibit. Free intracellular Ca2+ concentration ([Ca2+]i) was measured in control and O2-exposed alveolar macrophages. Hyperoxic exposure did not alter [Ca2+]i in unstimulated cells. In controls, con A stimulated an immediate increase in [Ca2+]i followed by a rapid decrease and a second rise and fall. The second elevation was suppressed by verapamil or ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetraacetic acid or O2 exposure. The results of both the respiratory burst assays and measurement of con A-stimulated changes in [Ca2+]i suggest that Ca2+ entry involved in stimulus-response coupling is suppressed in cellular O2 toxicity.

Animals↗

Cloacal papillomas in psittacines.

Papilloma-like masses affecting the cloaca of 19 Amazons, 16 macaws, 3 parrots, 1 conure, and 1 parakeet were examined. Papillomatous lesions were characterized by proliferation of the lining epithelium on thin fibrovascular stalks. Carcinoma in situ was diagnosed in the cloaca of a macaw in addition to the other 16 macaws with papillomas. Papillomavirus group-specific antigens were not detected in any of the 41 lesions, using the peroxidase-antiperoxidase technique. The DNA extracts from 6 different frozen papillomas did not contain papillomavirus genomes detectable by Southern blot hybridization, using an African gray parrot cutaneous papillomavirus as a probe. Evidence of an infective agent was not found by electron microscopic examination of 8 of the papillomas. Inoculations of partially purified homogenates of a cloacal papilloma from a yellow-crowned Amazon did not induce lesion formation on cloacal mucosa of an adult yellow-crowned Amazon, green and yellow macaw, sulphur-crested cockatoo, or mollucan cockatoo.

Animals↗

An investigation into the effect of the IgG antibody system on the susceptibility of IgA-deficient patients to respiratory tract infections.

Serum IgG subclass concentrations and IgG-tetanus toxoid antibody (IgG-TTab) responses were measured in IgA-deficient patients with severe respiratory tract infections (n = 11), mild respiratory tract infections (n = 5) or no increased susceptibility to respiratory tract infections (n = 15). The severe infection group had lower IgG2 concentrations than the patients without infections (P less than 0.02) and was the only group with IgG2-deficient patients (36%). The number of sera in which IgG4 was not detected was higher in patients with severe infections than in both normal controls (45% vs 10%, P less than 0.01) and the other IgA-deficient patients (45% vs 20%), in part explained by a strong association with IgG2 deficiency. Subnormal IgG-TTab responses were demonstrated in 45% of patients with severe infections but in only one patient from each of the other two groups. Five patients with IgG2 deficiency and/or subnormal IgG-TTab responses were treated with gammaglobulin and apparently improved. There was a high serum concentration of IgG1 in 35% and IgG3 in 19% of the 31 patients, predominantly in those without severe infections. Thus a proportion of IgA-deficient patients have additional defects of IgG; IgG1 and IgG3 antibody responses may compensate for the IgA deficiency in asymptomatic patients.

Adolescent↗

Effects of t-butyl hydroperoxide on NADPH, glutathione, and the respiratory burst of rat alveolar macrophages.

The effects of t-butyl hydroperoxide on glutathione and NADPH and the respiratory burst (an NADPH-dependent function) in rat alveolar macrophages was investigated. Alveolar macrophages were exposed for 15 min to t-butyl hydroperoxide in the presence or absence of added glucose. Cells were then assayed for concanavalin A-stimulated O2 production or for NADPH, NADP, reduced glutathione, glutathione disulfide, glutathione released into the medium and glutathione mixed disulfides. Exposure of rat alveolar macrophages to 1 X 10(-5) M t-butyl hydroperoxide causes a loss of concanavalin A-stimulated superoxide production (the respiratory burst) that can be prevented or reversed by added glucose. Cells incubated without glucose had a higher oxidation state of the NADPH/NADP couple than cells incubated with glucose. With t-butyl hydroperoxide, NADP rose to almost 100% of the NADP + NADPH pool; however, addition of glucose prevented this alteration of the NADPH oxidation state. Cells exposed to 1 X 10(-5) M t-butyl hydroperoxide in the absence of glucose showed a significant increase in the percentage GSSG in the GSH + GSSG pool and increased glutathione mixed disulfides. These changes in glutathione distribution could also be prevented or reversed by glucose. With 1 X 10(-4) M t-butyl hydroperoxide, changes in glutathione oxidation were not prevented by glucose and cells were irreversibly damaged. We conclude that drastic alteration of the NADPH/NADP ratio does not itself reflect toxicity and that significant alteration of glutathione distribution can also be tolerated; however, when oxidative stress exceeds the ability of glucose to prevent alterations in oxidation state, irreversible damage to cell function and structure may occur.

Animals↗

Low pressure/low flow voiding in younger men: psychological aspects.

Low pressure/low flow voiding in young and middle-aged males in the absence of outflow tract obstruction has been reported as being associated with anxiety and a high incidence of dyspepsia. To assess objectively the psychological basis of this condition, an unselected group of 50 men aged 25 to 55 years was evaluated by psychiatric interview, questionnaires and urodynamic tests. In addition, patients involved in an earlier study were psychologically evaluated. Low pressure/low flow voiding was demonstrated in three (6%) of the new patients. This voiding pattern was related to a long preceding history, stress-dependent symptoms and difficulty in voiding in public urinals. When compared with a control population, the experimental group scored significantly higher on measures of psychoneurosis. It is recommended that surgery be avoided in these patients and that simple behavioural therapy may be most appropriate.

Adult↗

Serum immune complexes in systemic sclerosis: relationship with precipitating nuclear antibodies.

In a comparative study of antinuclear antibodies (ANA) and immune complexes in the serum of 43 patients with systemic sclerosis (SS) ANA were detected by indirect immunofluorescence on Hep 2 cells and/or double immunodiffusion in 90% of patients, while immune complex assays were positive in 32% of patients. The immune complex assays were positive only in sera containing antibodies to Scl 70, n-RNP, Ro, and La. The presence of immune complexes in SS sera is therefore related to ANA specificity. This might explain the variable findings of several previous studies of immune complexes in SS.

Adult↗

Headache at high altitude is not related to internal carotid arterial blood velocity.

The cause of headache in persons going to high altitude is unknown. Relatively severe hypoxemia in susceptible subjects could induce large increases in cerebral blood flow that then could initiate the headache. Thus we measured noninvasively, by Doppler ultrasound, changes in internal carotid arterial blood velocity (velocity) in 12 subjects in Denver (1,600 m) and repeatedly up to 7 h at a simulated altitude of 4,800 m (barometric pressure = 430 Torr). Six subjects, selected because of prior history of high-altitude headache, developed comparatively severe headache at 4,800 m, and four subjects, without such history, remained well. Two subjects developed moderate headache. Velocity at 4,800 m did not correlate with symptom development, arterial O2 saturation, or end-tidal PCO2. Also, neither velocity nor blood pressure was consistently elevated above the Denver base-line values. During measurements of hypercapnic ventilatory response in Denver, velocity increased linearly with end-tidal PCO2, confirming that our Doppler method could demonstrate an increase. Also, 30 min of isocapnic or poikilocapnic hypoxia caused small increases in velocity (+8 and +6%) during the base-line measurement at low altitude. Although even a small increase in cerebral perfusion could contribute to headache symptoms at high altitude, cerebral blood flow does not appear to play a primary role.

Adult↗

High altitude pulmonary edema and exercise at 4,400 meters on Mount McKinley. Effect of expiratory positive airway pressure.

Breathing against positive expiratory pressure has been used to improve gas exchange in many forms of pulmonary edema, and forced expiration against resistance during exercise has been advocated for climbing at high altitude as a method to optimize performance. To evaluate the effect of expiratory positive airway pressure (EPAP) on climbers with high altitude pulmonary edema (HAPE) and on exercise at high altitude, we studied four climbers with HAPE at rest and 13 healthy climbers during exercise on a bicycle ergometer at 4400 m. We measured minute ventilation (VI, L/min), arterial oxygen saturation (SaO2 percent), end-tidal carbon dioxide (PACO2, mm Hg), respiratory rate (RR), and heart rate (HR) during the last minute of a five minute interval at rest in the climbers with HAPE, and at rest, 300, and 600 kpm/minute workloads on a bicycle ergometer in the healthy subjects. The HAPE subjects demonstrated an increased SaO2 percent, no change in HR or VI, and a decrease in RR on EPAP as compared to control. In normal subjects, SaO2 percent, VI, and heart rate were significantly higher on EPAP 10 cm H2O than 0 cm H2O control (p less than 0.01, 0.01, and 0.05, respectively). The RR and PaCO2 were not significantly different. In summary, EPAP improves gas exchange in HAPE subjects at rest. The EPAP in normal subjects at high altitude resulted in a higher SaO2 percent at the expense of a higher VI and higher HR. These results suggest that the work of breathing is higher and the stroke volume lower on EPAP. The positive pressure mask may be an effective temporizing measure for victims of HAPE who cannot immediately go to a lower altitude.

Adult↗

The IgG4 subclass is associated with a low affinity antibody response to tetanus toxoid in man.

The amount and relative affinity of antibodies to tetanus toxoid were measured, following immunization, in patients with chronic or recurrent acute chest infections and in healthy controls. The responding patients and controls produced similar amounts of antibody and, although antibody affinity was higher in the controls compared to the patients, the differences were not significant. Most individuals (65%) produced antibody of the IgG1 subclass with little or no IgG4 antibody, but in the remainder antibody was either predominantly IgG4 (29%) or equally distributed between the IgG1 and IgG4 subclasses (6%). Antibody affinity was significantly lower in both patients and controls producing IgG4 antibodies compared to those with a predominantly IgG1 response, and antibody affinity increased with the amount of IgG1 antibody present. These results provide preliminary evidence of an association between low antibody affinity and the IgG4 subclass in man.

Acute Disease↗

Purification and characterization of an inducible dissimilatory type sulfite reductase from Clostridium pasteurianum.

An inducible sulfite reductase was purified from Clostridium pasteurianum. The pH optimum of the enzyme is 7.5 in phosphate buffer. The molecular weight of the reductase was determined to be 83,600 from sodium dodecyl sulfate gel electrophoresis with a proposed molecular structure: alpha 2 beta 2. Its absorption spectrum showed a maximum at 275 nm, a broad shoulder at 370 nm and a very small absorption maximum at 585 nm. No siroheme chromophore was isolated from this reductase. The enzyme could reduce the following substrates in preferential order: NH2OH greater than SeO3 (2-) greater than NO(2-) 2 at rates 50% or less of its preferred substrate SO3(2-). The proposed dissimilatory intermediates, S3O6 (2-) or S2O3(2-), were not utilized by this reductase while KCN inhibited its activity. Varying the substrate concentration [SO3(2-)] from 1 to 2.5 mumol affected the stoichiometry of the enzyme reaction by alteration of the ratio of H2 uptake to S2- formed from 2.5:1 to 3.1:1. The inducible sulfite reductase was found to be linked to ferredoxin which could be completely replaced by methyl viologen or partially by benzyl viologen. Some of the above-mentioned enzyme properties and physiological considerations indicated that it was a dissimilatory type sulfite reductase.

Arabidopsis Proteins↗

Sexual histories, attitudes, and behavior of schizophrenic and "normal" women.

Data on sexual history and current sexual functioning were collected from 20 schizophrenic women and 15 normal volunteers. Schizophrenic women, compared to normal volunteers, reported a higher incidence of sexual abuse premorbidly, particularly during childhood, as well as after the onset of frank psychotic symptomatology. Patients also learned about sexual interaction and began menstruating earlier and had more negative feelings toward menstruating. In addition, psychosexual dysfunctions were markedly more common among the schizophrenic women, both pre- and postmorbidly. Compared to only 13.4% of the normal women, 60% of the schizophrenic women had never experienced orgasm. Patients did not believe that sexual activity worsened their illness, and only 20% of the patients thought their illness had adversely affected their sexual behavior.

Adult↗

Psychiatric hospital admissions in Bristol. I. Geographical and ethnic factors.

The distribution of in-patient psychiatric admissions throughout the city of Bristol during the period 1978-1981 is described. High rates were found from the central urban areas of low social class and with a high concentration of immigrants. The findings suggest that immigrant groups (mainly of West Indian origin) are no more likely than others living in the city centre to become psychiatric hospital in-patients, but when they do so, they are more likely to require compulsory admission.

Commitment of Persons with Psychiatric Disorders↗

Psychiatric hospital admissions in Bristol. II. Social and clinical aspects of compulsory admission.

Three groups of patients admitted compulsorily from populations with markedly different rates of compulsory psychiatric admissions were compared on a range of social and clinical data. Whilst West Indian and white patients from inner city areas differed in many respects, they were both more likely than other patients to be referred to the psychiatric services through police agencies, with little GP involvement and were often admitted from public places following disturbed behaviour. However, levels of violence and threatening behaviour were no higher among inner city patients, black or white, and once admitted, these groups showed similar treatment compliance to white patients who had been admitted compulsorily from suburban areas. Implications for primary care and delivery of psychiatric services are discussed.

Adult↗

Antibody-dependent cellular cytotoxicity of human vascular endothelium in systemic sclerosis.

Sera from 39 patients with systemic sclerosis were examined for a cytotoxic effect on human umbilical vein endothelium. Although none of the sera produced direct cytotoxicity of 51Cr-labelled endothelial cells, even with added complement, nine sera did produce increased 51Cr release when co-cultured with endothelial cells and normal human peripheral blood mononuclear cells. The effector cells involved in this cytotoxicity possessed Fc receptors but were non-T and non-adherent while the responsible serum factor(s) was present in IgG containing fractions. This cytotoxicity tended to occur in patients with both circulating immune complexes and precipitating antibodies to nuclear and cytoplasmic antigens who, as a group, had more severe and extensive visceral disease than those without such serological abnormalities. Control studies using sera from both 27 normal controls and 19 patients with either diabetes or extensive athero-sclerotic vascular disease failed to reveal any similar cytotoxicity.

Adult↗

Systemic antibody deficiency in patients without serum immunoglobulin deficiency or with selective IgA deficiency.

Serum IgG tetanus toxoid antibody (IgGTTab) concentrations were measured in patients with chronic chest infections or recurrent acute chest infections following immunization and compared with results obtained in a group of 43 controls. Apart from selective IgA deficiency in some patients, all had normal or high serum immunoglobulins. Using an enzyme linked immunosorbent assay (ELISA) for IgG TTab, antibody was present following one immunization in all controls who had previously been immunized and following two immunizations in those not previously immunized. Ninety-seven and a half per cent of controls had a serum antibody concentration of greater than 4 micrograms/ml. Following the same immunization schedule, eight of 45 (18%) patients with chronic chest infections and three of 11 (27%) patients with recurrent acute infections had a serum IgG TTab of less than 4 micrograms/ml. The three patients with a low IgG TTab concentration and recurrent acute infections all had selective IgA deficiency. Two of these patients have benefited from injections of normal human immunoglobulin. It is suggested that systemic antibody deficiency as a cause of chronic or recurrent respiratory tract infections cannot be excluded by measuring serum immunoglobulin concentrations alone and that it is of value to measure antibody responses following immunization.

Adult↗

Serum IgG subclass concentrations in healthy adults: a study using monoclonal antisera.

IgG subclass concentrations have been measured in the sera of 172 healthy adults using monoclonal antisera. 'Normal ranges' are given. The findings were similar to those of previous studies of European populations but differed from the findings of the only other study of a large British population. In particular, low proportions of IgG4 in a British population have not been confirmed. IgG4 concentrations were higher in males than females (P = less than 0.00003) and IgG3 concentrations were higher in females than males (P = 0.034).

Adult↗

Hypercalcaemia in a psychogeriatric population.

Serum calcium concentration was estimated, via a multichannel analyser, in all patients admitted to a 25 bed psychogeriatric inpatient unit and associated day hospital. Case notes of 629 consecutive admissions over a 42 month period were studied, and the prevalence of hypercalcaemia found to be 0.7 per cent, close to that estimated for the general population. Cases of hypercalcaemia with psychiatric symptoms, undetected medically because of vague and non-specific physical symptoms, do not appear in excess in a psychogeriatric population.

Aged↗