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Biomedical subjects

J S Beck

Publications and source records attributed to J S Beck.

At least 145 records · Page 8Linked to original sources
PubMed1985

Haptoglobin: an immunoregulatory role in tuberculosis?

A significant correlation was found between levels of haptoglobin in sera from Indonesian patients with tuberculosis and the extent to which these sera suppressed mitogen-driven activation of normal lymphocytes in vitro. As in a previous study we showed that there was an inverse relationship between haptoglobin levels and the circulating lymphocyte count in the same group of patients, it is now suggested that this protein has an immunoregulatory role in tuberculosis. Similar observations have been made by other workers on patients with cancer. There was no difference in the distribution of the 3 allotypes of haptoglobin in patients and healthy subjects nor was there any association between such allotypes and the lymphocyte count, the dermal reactivity to tuberculin or the degree of suppression.

Agglutination Tests↗
PubMed1985

Lymphocyte subsets and Langerhans cells in allergic and irritant patch test reactions: histometric studies.

This study has attempted to distinguish between allergic and irritant reactions to patch tests by semiquantitative histological methods. The extent of perivascular chronic inflammatory infiltrate at 72 h in irritant patch test reactions to sodium lauryl sulphate was shown to be small and very consistent, whereas in allergic reactions to nickel sulphate it was generally larger and more variable in size (p less than 0.02). The two major lymphocyte subsets (T4 and T8) were randomly intermixed in both types of reaction and formed the major component of both the perivascular and diffuse dermal infiltrate, without any evidence of selective migration. The T4:T8 ratios were similar in focal and diffuse infiltrates. The number of T6 dendritic (putative Langerhans) cells in the epidermis (per mm inner epidermal length) was usually greatly reduced in irritant reactions (5-16 mm-1, mean 10 mm-1) but remained within normal limits in allergic reactions (6-33 mm-1, mean 21 mm-1) (p less than 0.001). Comparable results were seen with other irritants (mercuric chloride and benzalkonium chloride) and other allergens (neomycin sulphate, ethylene diamine and potassium dichromate). In additional experiments, pairs of biopsies were taken from the reaction and from adjacent unaffected skin. The T6 cell density in the epidermis did not significantly differ between allergic reactions and control skin. By contrast, the irritant reactions had fewer T6 cells than the control skin (p less than 0.001).

Dermatitis, Atopic↗
PubMed1985

Observer variability in reporting of breast lesions.

The consistency of histological diagnosis of breast lesions by members of the panel was studied using a simplified six point classification system that covered the range from normal tissue to invasive carcinoma. In a representative set of 40 sections of the range of breast disease included in the Trial for Early Detection of Breast Carcinoma (the consecutive series), there was, overall, 82% agreement between the diagnoses submitted by members of the panel: diagnosis was virtually consistent (99% agreement) for frankly invasive carcinoma, but there was much greater variability in the diagnosis of borderline lesions. Diagnostic consistency was greatly improved when two categories only (benign and malignant) were considered (94% agreement). The diagnostic consistency of individual pathologists was studied by recirculating the sections: the overall agreement was 78% and, again, most of the inconsistencies occurred when borderline lesions were diagnosed. Additional studies were undertaken on borderline lesions that had been flagged during the first two years of the trial (the borderline series). Unsurprisingly, there was less agreement among the pathologists when all six diagnostic categories were used (70% and 77% for the specimens from the first and second years, respectively), but consistency was greatly improved when classification was simplified to either benign or malignant (86% and 91%, respectively). The diagnoses submitted by individual pathologists were found to deviate from the "majority" diagnosis to a relatively minor extent: each pathologist was generally consistent in either under-diagnosing or overdiagnosing in both the consecutive and borderline series.

Breast↗
PubMed1985

T4 lymphopenia in patients with active pulmonary tuberculosis.

The numbers of cells bearing the T3 (pan-T cell), the T4 (putative helper/inducer cells), the T8 (putative suppressor/cytotoxic cells) and B cell phenotypic markers were counted in venous blood samples from 26 newly diagnosed pulmonary tuberculosis patients and 29 healthy controls from East Java. The absolute T cell count was lower in the patients and T4 cells were fewer in patients (mean 748/mm3) than in controls (mean 1,043/mm3), but there were no significant differences in total T8 cell and B cell counts between patients and controls. The T4:T8 ratio was not disturbed in many patients, but it was less than 1.6 in 11 of 26 patients and in only three of 29 controls: this ratio was less than 1.2 (the lower limit of 'normal') in six patients but no controls. The intensity of the T4 lymphopenia was unrelated to the extent of the lesion seen radiologically or the size of the skin test reaction to PPD. Levels of interferon-alpha were not elevated in the serum of any of the patients or controls. It is suggested that the T4 lymphopenia was a reaction to the mycobacterial infection and not a manifestation of underlying secondary (acquired) immune deficiency.

Adolescent↗
PubMed1985

Quantitation of the granuloma fraction in leprosy skin biopsies by planimetry.

The proportion of the dermis occupied by granuloma in histological sections of skin biopsies from leprosy patients is known as the granuloma fraction. It can be estimated by direct microscopy on a scale of tenths using a low-power objective. We have compared this method with measurement of the granuloma fraction by planimetry, which gives comparable results but is much more accurate and precise. The implications of these findings for the objective assessment of the effects of treatment regimes on leprosy are discussed.

Biopsy↗
PubMed1983

The sensitivity of peripheral blood lymphocytes to growth inhibition by hydrocortisone is not determined by their OKT4:OKT8 ratio.

Normal adult human subjects show considerable variation in sensitivity to depression of the activation phase of mitogen-induced lymphocyte growth by the natural glucocorticoid, hydrocortisone. In a study of 21 subjects, the slope of the log-dose response to hydrocortisone was unrelated to the relative numbers of cells in the two major T-cell subpopulations stained by the OKT4 and OKT8 monoclonal antibodies. It is concluded that the extent of the glucocorticoid-induced suppression of early mitogen-stimulated lymphocyte growth is probably not determined by relative numbers of the various immunoregulatory lymphocytes.

Adult↗
PubMed1983

Effect of anaesthesia and surgery on the pre-S-phase cell cycle kinetics of mitogen-stimulated lymphocytes of previously healthy people.

The influence of general anaesthesia, and of operative surgery, on immune responsiveness was studied in blood obtained from 26 women undergoing laparoscopic sterilization (minor operation group) and in 14 women undergoing abdominal hysterectomy (major operation group). Since immunity depends ultimately on clonal expansion of lymphocytes, the growth potential of peripheral blood lymphocytes was studied in tissue culture by mitogen stimulation. There was no evidence of any change in either the number of responding cells (those that have left the resting G0-phase and responded to mitogen stimulation by entering the G1-phase of the first cycle of growth) or in the rate at which cells grow in volume during the period of study. It was concluded that there was no evidence that anaesthesia, or surgery, impaired this aspect of the immune response in our patients, but the design of the experiments does not allow comment on other aspects of the immune response such as antigen presentation, immunoregulation and effector mechanisms, which are superimposed on the basic clonal expansion mechanisms studied in this investigation. Incidentally, we noted that the standard method for isolation of lymphocytes from peripheral blood frequently yielded highly contaminated preparations: if this fallacy was not appreciated, tests with contaminated lymphocytes could be misinterpreted as showing depression.

Adult↗
PubMed1983

Some tetracycline drugs suppress mitogen-stimulated lymphocyte growth but others do not.

Eight tetracycline drugs were tested for inhibitory effect on phytohaemagglutinin (PHA) stimulated growth (measured by [3H]-TdR uptake) of peripheral blood mononuclear cells: at least 26 normal subjects were tested with each drug. Doxycycline reduced DNA synthesis appreciably at concentrations within and just above the therapeutic range of blood levels: it was the most potent inhibitor, but demeclocycline, methacycline and minocycline had similar, if less potent, effects. Tetracycline, oxytetracycline, chlortetracycline and clomocycline did not inhibit DNA synthesis of 3-day cultures even at concentrations five to ten times greater than the therapeutic blood level. Volume spectroscopy measurements showed that none of the eight tetracycline drugs interfered with the recruitment of cells into G1-phase growth of the first cell cycle after PHA stimulation.

Adult↗
PubMed1983

Simulation of association curves and 'Scatchard' plots of binding reactions where ligand and receptor are degraded or internalized.

Frequently during the course of binding to a receptor, ligand is degraded. In some preparations receptor is degraded. And with isolated cell preparations, ligand and/or receptor may be internalized. Here we present a mathematical model in which the binding and other reactions are combined. The resulting set of differential equations is solved numerically to simulate association curves and the resulting values of bound and free ligand are used to construct Scatchard plots. Where non-ideal conditions exist, the Scatchard plots are generally curvilinear. Dependence of this curvilinearity - on time of measurement of free and bound ligand, on degradation and internalization of ligand, and on degradation and internalization of receptor - is shown. Equilibrium constants derived from the Scatchard plots are generally incorrect but the derived receptor concentration is often correct. The simulations suggest experimental possibilities for distinction among the several side reactions in ligand-receptor binding systems.

Binding Sites↗
PubMed1983

In vitro effects of doxycycline and tetracycline on mitogen stimulated lymphocyte growth.

Doxycycline and tetracycline were tested for inhibitory effect on PHA stimulated growth (measured by [3H]-TdR uptake) of peripheral blood mononuclear cells from 26 normal subjects. Doxycycline reduced DNA synthesis appreciably at concentrations within and just above the therapeutic range of blood levels: tetracycline did not inhibit DNA synthesis of 3 day cultures even at concentrations five-10 times greater than the therapeutic blood level. Detailed studies on the action of doxycycline by volume spectroscopy and RNA flow cytofluorimetry indicated that this drug did not influence the recruitment of cells into the first G1-phase. Cell counts, DNA flow cytofluorimetry and autoradiography after pulsed exposure to [3H]-TdR showed a reduction in the numbers of growing cells in 2 and 3 day cultures in the presence of doxycycline compared with those containing tetracycline at the same concentration.

Adult↗
PubMed1983

The destruction of peripheral-blood lymphocytes by extracorporeal exposure to ultraviolet radiation.

Venous blood from healthy adult human donors was circulated through a wholly extracorporeal circuit for periods up to 140 min without apparent damage to the lymphocytes. However, when the blood was exposed to short-wave ultraviolet radiation (UVC; lambda, 254 nm), separated mononuclear cells showed a depressed response to mitogen stimulation: the magnitude of this effect was related to the duration of exposure. This depression cannot be attributed to change in blood pH, partial pressures of oxygen and carbon dioxide, temperature of cell trauma. Plasma from irradiated blood was less satisfactory than non-irradiated plasma for the support of growth of phytohaemagglutinin-stimulated lymphocytes in culture, probably because of depletion of essential nutrients, and there was little evidence for the generation of growth-inhibitory humoral factors. The UVC-irradiated lymphocytes had normal ultrastructure when removed from the extracorporeal circuit, but underwent apoptosis and necrosis during the first day of tissue culture with or without mitogen stimulation.

Adult↗
PubMed1983

The effect of C3 levels on yeast opsonization by normal and pathological sera: identification of a complement independent opsonin.

The ability of 150 normal and pathological sera to opsonize yeast for uptake by isolated human polymorphonuclear leucocytes has been studied. Phagocytosis was measured by an assay depending on electronic particle counting to measure yeast uptake and by a new fluorometric assay which is able to distinguish particle adherence from true phagocytosis. The opsonic activity of normal human serum was heat labile and depended markedly on C3 levels. The sera of 6% of healthy young adults (three from 45) and 8% of healthy donors aged 65-88 (four from 57) showed defective opsonization in spite of normal C3 and CH50 levels. Thirty-eight pathological sera with low C3 levels showed defective opsonization. However, three sera with low C3 levels showed apparently normal opsonic activity. The opsonin from two of these sera was characterized. It was heat stable, had apparent mol.wt of 400,000 and was active in serum free media. The opsonin was absorbed by immobilized Staphylococcus aureus and by gelatin-Sepharose, suggesting that it is related to fibronectin. Fibronectin from normal human sera prepared by affinity chromatography on gelatin-Sepharose was not opsonic in this system.

Adult↗
PubMed1982

Mechanisms of phytohaemagglutinin (PHA) stimulation of normal human lymphocytes: 'trigger' 'push' or both?

The growth in volume of human peripheral blood lymphocytes after stimulation with various concentrations of PHA was measured with an electronic particle counter. The percentage of growing cells and averaged values describing their growth rates during the elapsed period of culture were estimated by fitting to the observed data the volume distributions derived from a mathematical model. With sub-optimal doses, the percentage of cells stimulated , and their incremental growth rate, increased with increasing dose of PHA, but the time-course of recruitment into the G1-phase was similar with all PHA concentrations studied. The results provide strong support for the 'trigger' hypothesis that there is a distribution of stimulation thresholds within the lymphocyte population: consequently, increasing mitogen concentration will be expected to result in increased numbers of responding cells within the suboptimal concentration range.

Adult↗
PubMed1982

Mitogen stimulation of peripheral blood lymphocytes of duodenal ulcer patients during treatment with cimetidine or ranitidine.

During a double-blind randomised clinical trial of cimetidine and ranitidine in the management of duodenal ulcer, the response of patients' peripheral blood lymphocytes to optimal mitogenic stimulation in vitro has been measured. Treatment with cimetidine, but not ranitidine, was associated with a significant increase in the proportion of peripheral blood lymphocytes responding to this optimal mitogenic stimulation. We conclude that these effects of cimetidine may not be mediated at classical histamine H2-receptors.

Adult↗
PubMed1982

Mitogen-stimulated lymphocyte growth and chronic uraemia.

Lymphocytes were isolated from venous blood by the Böyum method from 36 patients with chronic renal failure: the preparations were more frequently and more heavily contaminated with non-lymphoid cells than the equivalent preparations from normal controls. Volume spectroscopy measurements showed that, in the samples without gross contamination, lymphocytes from uraemic subjects react to mitogen stimulation with normal pre-S-phase cell-cycle kinetics. In other experiments, plasma from uraemic patients was shown to be more potent than serum in inhibiting the growth of mitogen-stimulated lymphocytes from normal subjects, both in the first G1-phase and in replicative growth. Thus humoral suppression appears to be more important than a cellular defect in explaining the depressed responses of uraemic blood to mitogen stimulation.

Cell Cycle↗