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Biomedical subjects

J S Beck

Publications and source records attributed to J S Beck.

At least 109 records · Page 6Linked to original sources
PubMed1988

Transcutaneous measurement of PO2 and PCO2 in the dermis at the site of the tuberculin reaction in healthy human subjects.

The respiration of the skin at the site of a delayed hypersensitivity reaction in tuberculin skin tests was studied by transcutaneous measurement of dermal oxygen and carbon dioxide tensions in normal individuals who had been immunized with BCG: six reactions were strong positives, four were weak positives, and four without induration were regarded as negative. The tcPO2 fell over the first 2 days of the reaction and remained low for the next 2 days: the severity of the changes was greater in the 'strong' reactions than in the 'weak' reactions. The tcPCO2 showed a reciprocal rise over the first 2 days and, although still high, tended to recover over the fourth day. These results indicate that local hypoxia and hypercapnia are prominent features of the positive tuberculin test, probably as a consequence of the respiration of the infiltrating lymphocytes and monocytes. It is likely that similar respiratory changes occur in those chronic inflammatory diseases where delayed hypersensitivity reactions make a contribution to the pathogenesis of the lesion.

Adult↗
PubMed1988

Effect of histamine and prostaglandin E2 on the microcirculation in the skin.

The response of the cutaneous microvasculature to two vasoactive mediators, histamine and prostaglandin E2, was measured by laser Doppler velocimetry. Four concentrations of histamine (1.01 to 65.1 X 10(-5) M, in fourfold dilutions) were injected intradermally into the forearms of six healthy subjects: Prostaglandin E2 (1.77 to 114.0 X 10(-8) M, also in fourfold dilutions) was injected several weeks later. The blood flow at the injection site was measured by laser Doppler velocimetry at five minute intervals until the response resolved. Both mediators produced hyperaemia with markedly accelerated cutaneous blood flow. Analysis of the dose response data showed that, for a given mediator, the differences in responses between subjects were not substantial and, in particular, that the kinetics of the decay of hyperaemia did not vary significantly between subjects. The response to histamine differed from that to Prostaglandin E2 in terms of time to maximum response, duration of maximum response and coefficient of decay.

Adult↗
PubMed1988

The effect of non-steroidal anti-inflammatory drugs on phytohaemagglutinin stimulated lymphocytes: relevance to possible therapeutic immunosuppression by fenclofenac.

Representatives of seven chemical groups of non-steroidal anti-inflammatory drugs were tested for their effect on activation and replicative growth of phytohaemagglutinin stimulated normal human lymphocytes in vitro at concentrations in the high therapeutic range, and, where possible, at 10 times that concentration. Fenclofenac was noted to be suppressive. Fenclofenac and diclofenac (the only available phenylacetic acid derivatives) were studied in more detail. The two drugs were equipotent in vitro. At low concentrations they enhanced replicative growth, due to cyclo-oxygenase inhibition of cells from some subjects, but at higher concentration they suppressed replicative growth of cells from all subjects, with only a minor effect on activation at very high concentration. However, the potency for clinical effect of fenclofenac and diclofenac is very different, because fenclofenac at therapeutic blood concentrations suppressed replicative growth in vitro, whereas therapeutic concentrations of diclofenac were inactive in lymphocyte suppression. It is suggested that the phenylacetic acid derivative non-steroidal anti-inflammatory drugs may have a composite action in vivo: by inhibition of cyclo-oxygenase they reduce prostaglandin production (and so produce some symptomatic relief in the same manner as the drugs in the other chemical groups of non-steroidal anti-inflammatory agents) and by suppression of lymphocyte replication they may interfere with the pathogenesis of certain chronic rheumatic diseases.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Blood flow velocity in cutaneous lesions of leprosy.

The velocity of blood flow in the cutaneous lesions of leprosy was measured by the noninvasive technique of laser-Doppler velocimetry in nine male patients, all under treatment with World Health Organization multidrug regimens. In three patients with stable borderline tuberculoid (BT) lesions, the blood-flow velocity was slightly faster over the lesion than that in adjacent uninvolved skin. There was no substantial difference between different sites at the center and edge of individual lesions in each patient, but there was some variation between subjects. In one other BT patient with a reversal reaction, blood-flow velocity was 20-fold greater than in adjacent uninvolved skin. In four patients with stable borderline lepromatous/lepromatous (BL/LL) disease, the blood-flow velocity was 3 to 9 times faster over the plaques than in adjacent skin. There was relatively little difference between measurements over comparable points at the edge and center of individual plaques, or between plaques in the same patient, but there were considerable differences between patients. A fifth BL patient in reversal reaction showed generally similar results to those found in the stable BL/LL patients. Histometric study of the biopsies taken immediately after blood-flow measurement from two different plaques on each of four BL patients showed a clear relationship between the granuloma fraction measured by planimetry and the blood-flow velocity. This finding suggests that laser-Doppler velocimetry might prove to be a useful, clinically acceptable, noninvasive technique for monitoring the severity of hyperemia as an early indication of reversal reaction during chemotherapy trials in leprosy patients.

Adult↗
PubMed1988

Changes in activation markers and cell membrane receptors on human peripheral blood T lymphocytes during cell cycle progression after PHA stimulation.

Phytohaemagglutinin (PHA)-stimulated peripheral blood lymphocytes were examined sequentially for changes in volume, the appearance of cell membrane receptors and nucleic acid synthesis. The kinetics of appearance of activation antigens were compared with the progress of the cell through the separate events of volume growth and nucleic acid syntheses, to determine points at which regulation of receptors may control further progress through the cell cycle. In all samples tested there was a consistent pattern of response in the proportion of cells progressing through the cell cycle. Most of the T cells increased in size (mean 82% at 24 hr), fewer cells entered the Gla/Glb phase with the onset of RNA synthesis (mean 68% at 48 hr) and even fewer entered DNA synthesis (mean 42% at 72 hr). The time-course of appearance and the number of cells expressing IL-2 receptors were almost identical with that of cells responding by RNA synthesis. A similar correlation was observed between expression of the transferrin receptor and DNA synthesis. Addition of anti-Tac antibody temporarily suppressed the onset of RNA synthesis and antibodies to the transferrin receptor suppressed DNA synthesis. These linkages are further evidence that IL-2 and transferrin are the specific signals for cellular RNA and DNA synthesis. With optimal concentrations of PHA, addition of IL-2 did not increase the proportion of cells bearing activation antigens or undergoing nucleic acid synthesis. Suboptimal concentrations of PHA produced a small reduction in the number of cells expressing the IL-2 receptor, but a much greater reduction in the rate of entry into RNA synthesis. There was a consistent increase in all activation parameters tested with the addition of IL-2, but the proportion of cells expressing the transferrin receptor and entering DNA synthesis was consistently lower than that of cells that expressed the IL-2 receptor or entered RNA synthesis. This suggests that regulation of the IL-2 receptor is not responsible for the reduction in the number of cells that proceed to proliferation. The CD2 antigen (T11(1] showed increasing expression in a step-wise fashion after activation, the increases coinciding with the onset of RNA and DNA syntheses.

Cell Cycle↗
PubMed1988

Diversity in migration of CD4 and CD8 lymphocytes in different microanatomical compartments of the skin in the tuberculin reaction in man.

The lymphocytes in the perivascular foci of tuberculin skin tests have a similar CD4:CD8 ratio to those in the peripheral blood, suggesting that these subsets do not show bias in their initial emigration. By contrast, the diffusely infiltrating lymphocytes show a relative preponderance of CD4 cells which is progressively greater in successive 250 micron layers into the dermis. A generally similar pattern is seen in healthy controls and in patients with untreated pulmonary tuberculosis, treated leprosy, haemophilia A and chronic obstructive lung disease (COLD) patients treated with prednisolone, but the gradient of increasing CD4:CD8 ratio with depth into the dermis is significantly less steep in patients with tuberculosis, haemophilia and prednisolone-treated COLD than in the healthy controls. Selective migration results in a relative preponderance of CD4 cells in the diffuse infiltrate and it is suggested that this is a mechanism likely to potentiate defensive reaction to Mycobacterium tuberculosis: any deficiency in selective migration may make immunological defences less effective and so contribute to the chronicity of the lesions of tuberculosis.

Cell Movement↗
PubMed1988

Reproducibility of histology in leprosy lesions.

The variability of three commonly used histological parameters in leprosy histology was examined within and between lesions on individual patients by taking two biopsies, either from opposing edges of the same lesion or from the edge of two separate lesions. There was little variation in granuloma fraction (GF), bacterial index (BI), or histological classification on the Ridley-Jopling scale between biopsies from opposing edges of the same lesion, but there was considerable variation in the GF between biopsies from the edge of different lesions. A lesser degree of variation was seen in the BI between different lesions, and there was little difference in histological classification between established lesions. Thus, it appears that local factors influence the size of the leprosy granuloma, but its histological composition and bacterial load are determined systemically.

Adult↗
PubMed1987

Suppression of growth of PHA-stimulated human lymphocytes by a novel steroid (RU 28 362) lacking the 21-OH group.

RU 28 362 is a novel synthetic steroid (lacking the 21-OH group) which reacts exclusively with the glucocorticoid receptor. It is therefore chemically different from the other natural and synthetic glucocorticoids in common use which also bind to a lesser extent to receptors for other classes of steroids. Aspects of the immunosuppressive effect of RU 28 362 were studied by comparing its suppressive effects on PHA-stimulated growth of human lymphocytes with those of hydrocortisone, betamethasone and the inactive analogue, 21-deoxyhydrocortisone. RU 28 362 was more potent than either hydrocortisone or betamethasone, but all three glucocorticoids had a parallel dose-response curve in suppression of the increase in cell volume that occurs with activation during the first day in culture. In studies on the time of appearance and density of IL-2 receptors during the first 3 days in culture, RU 28 362 was also somewhat more inhibitory and had a steeper dose-response curve than hydrocortisone or betamethasone. RU 28 362 was much more inhibitory and had a steeper dose-response curve than either hydrocortisone or betamethasone in inhibiting [3H]-TdR incorporation by 3-day PHA stimulated cultures. 21-deoxyhydrocortisone did not inhibit any aspect of PHA-stimulated lymphocyte growth.

Androstanols↗
PubMed1987

Mechanisms by which barbiturates suppress lymphocyte responses to phytohaemagglutinin stimulation.

Certain barbiturates (the intermediate- and short-acting drugs) reduce the growth of PHA-stimulated peripheral blood mononuclear cells, but phenobarbitone (a long-acting drug) is ineffective: replicative growth is more sensitive than activation. This action is associated with a marked reduction in the density of interleukin-2 receptors on the cell membrane and of the numbers of cells expressing them, but the growth rate cannot be restored by supplementation of the tissue culture medium with exogenous interleukin-2. The affected cells show swelling of the mitochondria and cytoplasmic fat globules: the presence of residual bodies and myelin figures indicate an increase in the rate of degradation of organelles. There was no appreciable increase in the number of necrotic cells seen on electron microscopy of cultures exposed to high concentrations of thiopentone or other potent barbiturates, but the presence of debris in the DNA cytogram at 72 h indicated some increase in the death rate of cells exposed to the growth suppressing barbiturates. It would be inadvisable to administer these short- and intermediate-acting barbiturates over long periods, particularly at high dosage, because of the potential danger of iatrogenic immunosuppression.

Adult↗
PubMed1987

Skin test responsiveness to four new tuberculins in patients with chronic obstructive airways disease receiving short term high doses of, or long term maintenance treatment with, prednisolone: clinical appearances and histometric studies.

The response to skin testing with tuberculins extracted from various species of mycobacteria was studied in 49 patients from Dundee with chronic obstructive airways disease. Seventeen had never been treated with steroids (group 1), 17 were receiving short term high doses of prednisolone (group 2) and did not have impaired Synacthen tests; 15 were receiving long term maintenance treatment and did have impaired Synacthen tests (group 3). Erythematous and indurated reactions were seen in a few patients, more commonly to antigens from Mycobacterium tuberculosis than to the other species: neither of the latter treatment groups showed appreciable reduction in reactivity compared with that of the group 1 patients. The number and microanatomical distribution of the T4 and T8 lymphocytes and the M3 bearing monocytes and macrophages was studied immunocytochemically in cryostat sections of biopsy specimens from the antigen injection sites. The density of these cells was significantly less in clinically negative reactions than in those with erythema or induration, but was unrelated to the presence or absence of a history of treatment with prednisolone. The T4:T8 ratio in the section as a whole was similar to that of the peripheral blood, but T8 cells were relatively more common in the perivascular and periappendicular foci, and T4 lymphocytes were predominant in the diffuse component of the infiltrate. I12 receptor bearing lymphocytes were uncommon: such cells were least common in the clinically negative reactions, but the number and distribution were apparently unrelated to the presence or absence of prednisolone treatment. It was concluded that currently accepted regimens of treatment with prednisolone did not reduce the effector arm of type IV (delayed type hypersensitivity) responses and so are unlikely to compromise this aspect of protective immunity.

Aged↗