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Biomedical subjects

G M Galbraith

Publications and source records attributed to G M Galbraith.

At least 37 records · Page 2Linked to original sources

In vitro suppression of human lymphocyte activity by minoxidil.

The in vitro effect of minoxidil on normal human lymphocyte activity was studied. At a concentration of 0.1 mg/ml, minoxidil significantly inhibited phytohemagglutinin-dependent lymphocyte DNA synthesis (p less than 0.05), and at 0.01 mg/ml, 0.05 mg/ml, and 0.1 mg/ml, it suppressed mitogen-dependent production of leukocyte migration inhibition factor (p less than 0.04, p less than 0.01, and p less than 0.01, respectively), without compromising cell viability. Minoxidil thus appears to exert a suppressive effect on normal human T-lymphocytes in vitro. The physiologic relevance of these findings remains uncertain.

Cell Migration Inhibition↗

Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro.

The in vitro effects of isoprinosine (ISO) on interleukin-2 (IL-2) production, the expression of Tac antigen (IL-2 receptor) on lymphocytes, and the ability of Leu 3(+) cells to absorb interleukin-1 (IL-1) were investigated in 10 patients with acquired immune deficiency syndrome (AIDS). In 9 of the 10 patients, production of IL-2 from mononuclear cells and Leu 3(+) cells was depressed; expression of Tac antigen on mononuclear cells and Leu 2(+) cells was found to be depressed in 9 of 10 patients. The ability of the Leu 3(+) lymphocytes to absorb IL-1 was depressed in all (four of four) patients studied. After ISO treatment, IL-2 production, Tac antigen expression and IL-1 absorption were restored to normal or near normal levels in most of the patients. These results suggest that ISO has an immunostimulating capacity in AIDS patients and that the potential of ISO in immune response restoration in AIDS patients deserves critical consideration.

Acquired Immunodeficiency Syndrome↗

One subset of patients with retinitis pigmentosa has immunologic defects.

Immunological evaluation of 20 patients with retinitis pigmentosa (RP) revealed significantly diminished circulating T-lymphocyte numbers and function and a high frequency of serum antibodies to human IgG in comparison with a healthy matched control population. However, these differences were due to severely abnormal results found in one subpopulation within the total patient group; this dichotomy was unrelated to the mode of inheritance or clinical severity of RP in individual patients. Thus, RP appears to be a syndrome rather than a disease and includes a form characterized by defective immunity. Whether this is involved in the pathogenesis of the retinal degenerative process is conjectural.

Antibodies, Anti-Idiotypic↗

An open-label trial of immunomodulation therapy with inosiplex (Isoprinosine) in patients with alopecia totalis and cell-mediated immunodeficiency.

Nine patients with alopecia totalis and associated defects in T lymphocyte function were admitted to an open-label trial of inosiplex therapy. All nine developed enhanced T cell function and seven had clinically significant hair regrowth. The immunologic response to inosiplex was dose-dependent in five patients. These data provide new information on the in vivo effects of inosiplex on the human immune system and support the hypothesis that disturbances of immunologic mechanisms may play a pathogenetic role in alopecia totalis in certain patients.

Adjuvants, Immunologic↗

Immunological profiles in alopecia areata.

Cell-mediated immunity and auto-immune phenomena were investigated in sixty patients with active alopecia areata of various degrees of severity. Serum auto-antibodies to thyroid antigens were detected in twenty-three patients. Examination of T-lymphocyte populations, lymphocyte DNA synthesis, and lymphokine production in response to mitogen stimulation revealed no differences between the sixty patients and matched healthy control subjects. However, patients with thyroid auto-immunity and/or the presence of alopecia totalis or universalis showed significant reductions in interactive T lymphocytes (recognized by rosette formation with human B lymphoblastoid cells) and diminished production of leukocyte migration inhibition factor in response to stimulation with phytohaemagglutinin. This suggests that immune mechanisms may be involved in the pathogenesis of alopecia areata which is associated with thyroid auto-immunity or which progresses to total hair loss.

Adolescent↗

Gm allotype associated resistance and susceptibility to alopecia areata.

IgG heavy chain (Gm) and kappa light chain (Km) allotypes were determined in 42 Caucasian patients with alopecia areata. There was a significant increase in frequency of Gm 1,2,3,17;5,13,21 (P less than 0.001), and a significant decrease in frequency of Gm 1,3,17;5,13,21 (P = 0.009), when results were compared to those of 105 normal healthy Caucasians from the same geographic area. These results can be explained by postulating dominant disease susceptibility and resistance genes in significant linkage disequilibrium with the haplotypes Gm1,2,17;21 and Gm1,17;21, respectively.

Adult↗

Autoantibodies and immunoglobulin allotypes in healthy North American Blacks of different age groups.

A population of 291 healthy North American Black subjects of different ages was studied for immunoglobulin (Ig) allotypes and the prevalence of autoantibodies, to determine possible associations between Ig allotypes and age, autoantibodies and age, and Ig allotypes and autoantibodies. Indirect immunofluorescence was used to detect anti-gastric parietal cell, anti-smooth muscle, anti-thyroid microsomal, anti-nuclear, and anti-mitochondrial antibodies. The sera were typed for the Ig allotypes Gm(1, 2, 3, 5, 6, 13, 14, 17, and 21) and Km(1) with a hemagglutination-inhibition assay. A significant association between advanced age and an increased prevalence of anti-nuclear antibodies was observed in females. There was no significant association between Ig allotypes and the autoantibodies tested. The results suggest that Ig allotypes are not involved in the development of autoantibodies in healthy Blacks.

Adolescent↗

Effects of thymosin and evidence of monocyte suppression of both T- and B-cell functions in two cases of 'common variable immunodeficiency'.

We have studied two patients with common variable immunodeficiency (CVID), impaired cell-mediated immunity, and high percentages of monocytes in their peripheral blood. Removal of monocytes from cultures of peripheral blood mononuclear cells from both patients increased the in vitro responses to phytohaemagglutinin (PHA) and concanavalin A (Con A) but not to purified protein derivative (PPD), as measured by [3H]thymidine uptake. Similarly, supernatants of monocyte cultures from both patients, unlike supernatants of normal monocytes, suppressed the in vitro responses to PHA and Con A but enhanced the response to PPD by cultured mononuclear cells from the patients and from normal donors. Addition of unfractionated mononuclear cells from both patients to normal mononuclear cells suppressed both pokeweed mitogen (PWM) stimulation and IgG production; this effect was abrogated by removal of monocytes from the patients' mononuclear cell populations. This effect of thymosin on both patients' mononuclear cells was assayed in vitro. Thymosin was ineffective in vitro with cells from the first patient; for the other patient, [3H]thymidine uptake by mononuclear cells stimulated with PPD increased, whereas uptake by Con A-stimulated cells decreased, as did the percentage of E rosette-forming cells, providing further evidence of heterogeneity of the CVID syndrome. The effects of thymosin were also dependent on monocytes.

Adult↗

Combined radiolabel-binding and immunocytochemical evaluation of receptor-ligand interactions. Studies of transferrin receptors on activated lymphocytes.

A protocol that involved both immunohistological and radiolabel-binding procedures was devised for the study of transferrin-receptor interactions. This composite approach yielded considerably more information than did either technique used alone, and also provided a simple means for exclusion of several common potential sources of error.

Fluorescent Antibody Technique↗

Expression of transferrin receptors on mitogen-stimulated human peripheral blood lymphocytes: relation to cellular activation and related metabolic events.

Mitogen-activated normal human peripheral blood lymphocytes bind transferrin to specific membrane receptors. In this study, lymphocytes stimulated with phytohaemagglutinin for 0-66 hr were examined to determine the relation of this phenomenon to cellular activation and related metabolic events. Transferrin receptors were first detected at 20-24 hr. This event was consistently preceded by RNA and protein turnover which commenced during the first 6 hr of culture, whereas initiation of DNA synthesis was detected concurrently with the appearance of receptors or slightly later (24-30 hr). Exposure of cells to inhibitors of RNA and protein synthesis early during culture (at 0 or 24 hr) prevented the expression of transferrin receptors, but also caused generalized metabolic failure, and abrogated cellular activation. In contrast, later addition of these agents at 48 hr did not interfere significantly with the process of activation, but did suppress the terminal increase in receptor-bearing cells observed during the final 18 hr in control cultures lacking inhibitor. After deliberate thermal stripping of receptors from activated cells, the reappearance of membrance binding sites which normally occurred within 30 min, was also blocked by cycloheximide, puromycin and actinomycin D. However, similar inhibition of DNA which was induced by hydroxyurea had much less effect upon both the initial appearance of receptors and their reappearance after ligand-induced depletion. These results demonstrate that the appearance of transferrin receptors upon human lymphocytes is dependent upon cellular activation and requires synthesis of protein and RNA.

Antimetabolites↗

Studies of the interaction between human transferrin and specific receptors on the trophoblast membrane.

The concept of specific receptors for maternal transferrin on the human syncytiotrophoblast membrane has been generally accepted for many years, but definitive evidence of their existence has been established only recently. In this study, experiments were performed to characterize transferrin receptors further, both on intact membranes and after solubilization. Intact, isolated membrane fragments were examined for transferrin binding, both qualitatively by immunofluorescence and quantitatively by radiobinding. The amounts of ligand bound varied inversely with the quantities of residual maternal transferrin remaining at the time of testing. Scatchard plots revealed that the calculated affinity (K alpha) and the number of receptors increased substantially when transferrin was removed by initial washing with chaotropic agents. After dissociation from the membrane by detergents, occupied receptors largely retained bound transferrin, and transferrin binding by unoccupied receptors was also preserved. The stability of such ligand:receptor complexes was considerably enhanced at pH 5.0, and was apparently unaffected by prior treatment with chaotropic agents. Specific immunoprecipitation of solubilized radioiodinated membrane with rabbit antiserum to human transferrin, followed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate under reducing conditions, indicated a relative molecular mass for the unoccupied receptor of 90,000. These results confirm the existence of high-affinity receptors for transferrin on the trophoblast, and also delineate certain potential pitfalls in studies of their interactions with ligand.

Chemical Precipitation↗

Placental immunopathology in gestational diabetes.

Gestational diabetes and insulin-dependent diabetes are characterized by distinct pathophysiological mechanisms. However, their presence in pregnancy poses similar risks to the fetus. It is possible that factors common to both diseases are responsible for the increased morbidity and mortality in offspring of such pregnancies. Recent studies of placentae from insulin-dependent diabetics revealed evidence of immunopathological change which may support the possible role of immunological factors in the complications of diabetic pregnancy. In the present study, we have similarly examined placentae derived from 30 pregnancies complicated by gestational diabetes and from 10 normal pregnancies. The most striking differences detected by immunofluorescence were increased amounts of clotting factors related to areas of fibrinoid necrosis, and large quantities of complement components C4 and C3 in the intervillous spaces and trophoblast basement membrane respectively. These results are similar to those found in placentae from insulin-dependent diabetics, suggesting that glucose intolerance in pregnancy, even of minor degree, is frequently associated with immunopathological processes that are reflected in the placenta.

Animals↗

Studies of antigenic components of the human syncytiotrophoblast membrane.

In order to initiate characterization of potentially immunogenic moieties on the human trophoblast membrane, antisera to native and detergent-solubilized normal trophoblast membranes were prepared in rabbits. By indirect immunofluorescence, these antisera reacted strongly with all villous structures in normal placentae and also with a panel of normal adult human tissues. Specificities to normal human serum components were then removed by solid-phase immunoabsorption. However, the resultant antisera still reacted weakly with differentiated, normal adult tissues, and additional absorption with normal adult liver homogenate was necessary to remove cross-reactivity completely. Such absorbed antisera gave undiminished and specific fluorescence of the syncytiotrophoblast plasma membrane, and specifically precipitated two protein species with approximate relative molecular masses of 148,000 and 62,000. However, they also reacted with PHA-activated peripheral blood lymphocytes, in addition to Chang liver and HeLa cell lines. These results indicate that, even after extensive absorption, trophoblast membrane antisera may retain reactivity for determinants shared with normal and transformed adult cells.

Animals↗