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Biomedical subjects

J S Beck

Publications and source records attributed to J S Beck.

At least 127 records · Page 7Linked to original sources

Cell death in granulomata: the role of apoptosis.

Unequivocal apoptosis were seen by light microscopy in examples of leprosy, sarcoidosis, tuberculosis, Crohn's disease and foreign body granulomata. A limited electron microscopic investigation showed typical apoptotic bodies in both sarcoid and leprosy granulomata. The number of apoptosis and mitoses in granulomata were counted and their densities calculated. The wide variation in the results between individual lesions may reflect differences in disease activity.

Cell Survival↗

Unresponsiveness to skin testing with bacterial antigens in patients with haemophilia A not apparently infected with human immunodeficiency virus (HIV).

Unresponsiveness to skin testing with PPD and tetanus toxoid was commonly seen in patients with haemophilia A but not infected with human immunodeficiency virus but was uncommon in controls. Vaccination history indicated that the unresponsive patients had not been immunised in childhood. Other tests of immune competence (skin tests with other antigens, lymphocyte stimulation with mitogens and antigens, and viral serology) showed that the haemophilia A patients had an adequate response to pathogens to which they had been exposed. Five of 12 such patients had a mild T4 lymphopenia, and this may have been related to parenteral administration of large quantities of protein.

Adolescent↗

Features of di George syndrome in a child with 45,XX,-3,-22,+der(3),t(3;22)(p25;q11).

A child with an unbalanced translocation resulting in monosomy for chromosomes 22 (q11----pter) and 3(p25----pter) is described. Although no immunological dysfunction could be demonstrated, the abnormalities found are similar to those seen in the di George syndrome which has been associated with monosomy for the same region of chromosome 22.

Chromosome Deletion↗

Association between Km1 immunoglobulin allotype and pulmonary tuberculosis in Indonesians.

Allotypes were determined in 121 cases of smear-positive pulmonary tuberculosis and 33 healthy controls from Indonesia. It was found that the occurrence of Km1 was significantly lower in patients than in controls (p = 0.011), and that phenotypes lacking G1m (17) and G3m(21) as well as Km1 occurred much more frequently among patients than controls (p = 0.0025). Some evidence for an allotypic influence on the antibody response to mycobacterial antigens was found. A lack of G1m(17) or G3m(21) was associated with increased antibody levels in the IgG2 subclass in control subjects and a lack of Km1 with decreased antibody levels in the IgG4 subclass in patients.

Antibodies, Bacterial↗

The mechanism of action of the factor in leprosy serum that inhibits the growth of mitogen-stimulated normal human lymphocytes.

A factor found in the serum of patients with leprosy that inhibits the growth of mitogen-stimulated normal peripheral blood lymphocytes has been studied. The inhibitor, previously identified as an IgG, has been shown to act by blocking the recruitment of lymphocytes into growth. It was not cytotoxic and did not inhibit the rate of growth of those lymphocytes that had been stimulated. The inhibitory activity was less potent if the serum was added after mitogen stimulation. The inhibitor, which could be absorbed by activated but not resting lymphocyte cultures, appeared to act by inhibition of an early event preceding the release of IL-2. The inhibition of mitogen stimulation was overcome by the addition of purified IL-2, although the inhibitor did not block the action of IL-2 on a long-term cultured IL-2-dependent cell line.

Adolescent↗

Specific antibody in the subclasses of immunoglobulin G in patients with smear-positive pulmonary tuberculosis.

Discrimination between patients with smear-positive pulmonary tuberculosis and healthy adults achieved by the assay of serum anti-mycobacterial antibodies in the major immunoglobulin class (IgG) was greatly improved by assay of antibodies in its four subclasses. By the former method, only 55 of 107 (51%) patients had antibody levels above the upper limit of 31 control sera, but 96 (90%) patients had levels above the upper control level in one or more of the IgG subclasses. Antibody levels in the IgA and IgM classes were less discriminative, but four patients with no elevated levels in the IgG subclasses had elevated IgA antibody levels, bringing the total of patients with significant serological changes compatible with tuberculosis to 100 (93.5%).

Antibodies, Bacterial↗

Characterization of a factor in leprosy serum that inhibits the growth of mitogen-stimulated normal human lymphocytes.

A factor that inhibits the growth of mitogen-stimulated lymphocytes from normal donors has been detected in the sera of patients with chronic leprosy. The inhibitory activity was detected with similar frequency in patients with tuberculoid or lepromatous leprosy, although higher levels of activity were detected in the latter. The factor reduced the growth in volume of the lymphocytes in the first 24 hr after stimulation, the synthesis of RNA during the first 3 days of culture and the replication of DNA in 72-hr cultures. All the inhibitory activity co-purified with IgG on gel filtration, ammonium sulphate fractionation and ion exchange chromatography. The activity was stable to heating at 56 degrees but labile at 100 degrees and was absorbed from serum or from purified IgG preparations by staphylococcal protein A. On gel filtration of the sera on Sephadex G-200, none of the activity appeared in the void volume, indicating that it is not due to immune complexes. We conclude that the activity is due to an IgG antibody and suggest that it is an autoantibody since the sera inhibited the growth of all donor lymphocytes tested.

Adolescent↗

The method of preparation of an antigen may influence the cellular reaction to it in skin tests for delayed hypersensitivity: comparison between responses to two different reagents prepared from Mycobacterium tuberculosis.

Antigen preparations extracted from Mycobacterium tuberculosis by different procedures--PPD and 'New tuberculin'--were compared with respect to the cytology of the Type IV reaction they elicit in the dermis. The numbers and microanatomical localization of cells of the major lymphocyte and monocyte subsets were measured histometrically in immunocytochemically-stained sections of biopsies of the 48 h reactions. Despite the close similarity in size of the external appearance of the reactions provoked by the two preparations, 'New tuberculin' elicited a more extensive perivascular infiltrate and more numerous diffusely infiltrating M3-bearing cells: the number of diffusely infiltrating CD4 and CD8 lymphocytes was similar in reactions against the two antigen preparations. Thus the method used to prepare a skin test reagent may affect the nature of the cellular reaction it provokes: differences in content of various classes of antigenic macromolecules are probably important, but the relative content of other irritant constituents may also be important.

Adolescent↗

Coagulation in cell suspensions: extensions of the von Smoluchowski model.

Recently, a long-range interactive force between erythrocytes has been proposed (Rowlands et al., 1981, 1982a,b) based on an apparent increase in the rate of aggregation of erythrocytes in an aqueous suspension over that predicted by one model of Brownian aggregation. Here, we examine the assumptions underlying this model and propose modifications compatible with the biological constraints on the model. The refined model is represented as a series of coupled differential equations representing the change in particle number density as a function of time. Numerical solution of these equations is consistent with the absence of an intercellular force.

Blood Coagulation↗

Measurement of skin swelling in the tuberculin test by ultrasonography.

A new method is described for non-invasive measurement of the thickness of the skin at the site of a skin test from the echo pattern of a pulsed ultrasonic (15 MHz) A-mode scanner. In tuberculin tests on normal volunteers, the skin thickness increased rapidly during days 1 and 2 and was usually greatest at day 4. The echogram measurements can be used to calculate the increase in skin volume and this is disproportionately greater than would be expected from measurements of the diameters of erythema and induration.

Adult↗

The effect of exposure of hospital employees to patients with tuberculosis on dermal reactivity to four new tuberculins.

An early (6-8 h) erythematous response to Purified Protein Derivative and to sonicate antigens (new tuberculins) prepared from Mycobacterium tuberculosis, M. vaccae, M. scrofulaceum, and M. leprae occurred much more frequently amongst hospital employees exposed to patients with tuberculosis than amongst factory workers. Biopsies taken from the skin test sites at 48 h revealed a more intense inflammatory cell infiltrate in response to PPD and the sonicate of M. tuberculosis, but not to the antigens of the other mycobacteria, amongst the hospital employees thus indicating a degree of specificity. The early response appears to be directed towards species specific antigens, but not, apparently, to the same as those that elicit the 48 h reactions. The hospital employees also had higher peripheral blood B-cell counts and total IgG levels, suggestive of an adjuvant effect. It is postulated that the early reaction results from repeated exposure to tubercle bacilli and the possible nature of the reaction is discussed.

Adult↗

Histometry of thyroids containing few and multiple nodules.

Histometric measurements were made on individual nodules and the internodular thyroid on glands from 15 patients without evidence of endocrine thyroid disease: some of the thyroids had multiple nodules. Measurements of the surviving internodular thyroid tissue showed that the various components were each within the normal range for thyroids from patients with no evidence of thyroid disease, but there were considerable deviations within a few glands in the colloid:epithelium ratio that were associated with histological appearances of dilated or collapsed acini. The interpretation of these appearances presented difficulties, but it was concluded that the balance of evidence favoured the inference that the internodular part of the gland was under physiological growth control at the time of study. The nodules varied in size: most contained proportionately less epithelium and more colloid than the internodular thyroid. It was concluded that the nodules were unlikely to be secreting autonomously in these patients.

Age Factors↗

The influence of killed Mycobacterium leprae and other mycobacteria on opsonized yeast phagocytosis.

The influence of killed mycobacteria on the metabolic burst associated with phagocytosis of opsonized zymosan by normal human polymorphonuclear leucocytes (PMNL) or monocytes was studied by chemiluminescence (CL) measurements. M. leprae reproducibly reduced the peak and total CL of both types of phagocyte to a small, but highly significant extent. Electron microscopy showed that M. leprae were phagocytosed: cells with ingested or adherent M. leprae phagocytosed fewer zymosan particles. M. leprae did not cause aggregation of the phagocytes or quenching of CL. M. lepraemurium did not influence the CL response to zymosan. Addition of M. tuberculosis caused an increased response with PMNL but not with monocytes.

Cell Aggregation↗

The cellular responses of tuberculosis and leprosy patients and of healthy controls in skin tests to 'new tuberculin' and leprosin A.

The density and distribution of T4 and T8 lymphocytes and of monocyte/macrophages at the site of skin tests with mycobacterial antigens was studied in pulmonary tuberculosis and leprosy patients and in healthy controls. Most of the inflammatory cells were located in perivascular and periappendicular foci in the dermis: the percentage of the dermis occupied by focal infiltrate was unrelated to the clinical measurement of the area of induration. There was a less intense diffuse infiltrate in the dermis between the foci, most marked in the papillary dermis and lessening progressively in deeper layers. In patients, diffusely infiltrating lymphocytes were more numerous (mainly due to an excess of T8 cells) in relation to extracts of the pathogen causing their disease than to extracts of the other organism: T8 cells were particularly numerous in reactions to Leprosin A in three of four partly treated leprosy patients who had been classified as tuberculoid at the time of diagnosis. The density of diffusely infiltrating macrophages showed a similar density gradient and selective concentration in response to active disease pathogens. However these cells were less numerous in partly treated leprosy patients than in controls and most frequent in untreated pulmonary tuberculosis patients. Selective migration of monocyte/macrophages and, to a lesser extent T8 cells, appears to be a prominent feature in the reaction of patient with active mycobacterial disease to antigens derived from the causative organisms: this suggests that it might become possible to distinguish direct reactions from cross-reactions in human delayed hypersensitivity reactions by identification of these histological features.

Adult↗

A comparison of the responsiveness to four new tuberculins among Indonesian patients with pulmonary tuberculosis and healthy subjects.

Multiple skin testing with reagents (new tuberculins) prepared from different mycobacterial species places individuals in three categories: those reacting to all reagents (Category 1), those reacting to none (Category 2) and those reacting to some but not all (Category 3). This pattern of reactivity led to the postulate that Category 3 individuals respond only to those antigens that are unique to each individual species, while Category 1 individuals respond to antigens common to all mycobacteria, though a few of the latter may be responding independently to the specific antigens of all the reagents used. The percentage of patients with tuberculosis responding to all of four new tuberculins was much lower than among healthy subjects--a pattern of reactivity observed previously in leprosy. These findings strongly suggest that patients with mycobacterial diseases fail to respond to shared mycobacterial antigens.

Antigens, Bacterial↗

pH changes in the dermis during the course of the tuberculin skin test.

The response of six healthy young adults to tuberculin skin testing was studied. Five subjects developed a typical delayed-type hypersensitivity reaction to PPD with a local rise in skin temperature, and the sixth showed a less intense response; a considerable increase in blood flow velocity was seen in all reactions. All subjects showed a fall in pH in the dermis during the course of the reaction: in four subjects the pH minimum occurred at the time when the changes of erythema and induration were most prominent, in one subject the pH fall preceded the maximal clinical changes, and in the remaining subject a substantial fall in pH occurred with only transient erythema. It was concluded that the local tissue acidosis had resulted from the greatly increased metabolic demand of the lymphocytes and monocytes attracted into the dermis as part of the type IV delayed-type hypersensitivity reaction, and that the concurrent reactive hyperaemia was insufficient to clear the acidic metabolic products of the greatly increased cell population.

Adult↗

Studies of cell death (apoptosis) and cell division in leprosy granulomas.

We have studied the histological changes across leprosy lesions by taking biopsies from the center and edge of the lesions and from the clinically uninvolved skin outside the lesions. A comparison of the granuloma fraction (GF) between biopsies from the center and edge of lesions and the adjacent unremarkable skin shows that the greatest GF is found at the edge of lesions, except in early tuberculoid (BT) cases when biopsies from the center have the greatest GF. Central healing of leprosy lesions occurs without tissue necrosis or appreciable fibrosis. Apoptosis, a form of individual cell death in living tissues, is known to be the mechanism of cell loss in a variety of situations, and we have found it to occur in leprosy lesions. Apoptotic activity is greatest at the edge of established tuberculoid lesions, but can be found in the center of the lesion in early cases. We, therefore, suggest that apoptosis is the mechanism by which epithelioid cells are lost during central healing in tuberculoid leprosy lesions. In the small number of multibacillary cases studied, apoptosis were found in biopsies from both the center and edge of the lesions. Mitoses can be found in biopsies from both lepromatous and tuberculoid lesions. However, the degree of mitotic activity does not appear to be related to the position of the biopsy within the lesion, and immigration of monocytes into the granulomas may be of greater importance than cell division in maintaining the numbers of epithelioid cells or macrophages present.

Cell Division↗

Determination of binding parameters in the presence of coupled reactions.

Components of a binding reaction may undergo nonbinding reactions: receptors may be degraded, internalized, or exchanged with cryptic sites; ligand may be degraded or compartmented. In such cases the parameters that characterize the system are not obtained from the usual equilibrium analyses. We have simulated the reactions of such systems and generated association curves, "Scatchard" plots, and "Scatchard-like" plots that permit the calculation of binding affinity and receptor number not normally calculable under nonequilibrium binding conditions. In particular, we show that certain coupled reactions produce local maxima and sigmoid shapes in association curves and that the maxima can be used to obtain affinities and receptor numbers.

Binding Sites↗