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Biomedical subjects

D A Lawrence

Publications and source records attributed to D A Lawrence.

At least 181 records · Page 10Linked to original sources

Determination of glutathione in lymphocytes and possible association of redox state and proliferative capacity of lymphocytes.

The glutathione (GSH) content of mouse T- and B-cells was determined and compared with the GSH content of human peripheral blood lymphocytes and human erythrocytes. Owing to the difficulty of obtaining large numbers of purified lymphocytes, a technique was developed to measure picomolar quantities of GSH. By this technique, mouse T- and B-cells, as well as mouse peripheral-blood lymphocytes, were found to contain approx. 30% of the GSH found in human peripheral-blood lymphocytes. The concanavalin A response of human peripheral-blood lymphocytes and human spleen cells was insensitive to 2-mercaptoethanol as well as to culture in 17% O2, whereas mouse lymphocyte responses were altered by 2-mercaptoethanol and inhibited by 17% O2. The capacity of human peripheral-blood lymphocytes, human erythrocytes, mouse T-cells and mouse B-cells to regenerate GSH stores after chemical oxidation by diamide was tested, and it was found that mouse cells were less capable of regenerating GSH than human erythrocytes or human peripheral-blood lymphocytes. In addition, the latter lymphocytes were less sensitive to oxidation of GSH and to inhibition of proliferation by diamide.

Animals↗

Heavy metal modulation of lymphocyte activities--II. Lead, an in vitro mediator of B-cell activation.

Investigation of the immunopotentiating effect(s) of Pb2+ on the humoral immune response has provided evidence that a heavy metal can alter the proliferation and differentiation of B-cells. Pb2+ interacted with B-cells to enhance both their proliferation and their differentiation into sheep red blood cell (SRBC)-specific PFC. Preincubation of B-cells with Pb2+ for only 1 h enhanced their activities. Enhancement of in vitro humoral immunity to SRBC was due to direct Pb2+ activation of B-cells and enhancement of T-cell help. Furthermore, Pb2+ and the cyclic nucleotides dibutyryl cyclic adenosine monophosphate (DBcAMP) or cyclic guanosine monophosphate (cGMP) worked in a synergistic manner to enhance the B-cell proliferation, and Pb2+ and DBcAMP synergistically enhanced PFC development. Ni2+, which had been shown to enhance PFC development in cultures of spleen cells in a manner equivalent to Pb2+, did not enhance PFC development in B-cell cultures as well as Pb2+ and did not produce synergistic effects with DBcAMP or cGMP. The possible mechanisms by which Pb2+ enhances B-cell activities and the implications of these effects are discussed.

Animals↗

In vivo and in vitro effects of lead on humoral and cell-mediated immunity.

The humoral and cell-mediated immune responses of murine lymphocytes exposed to lead in vivo and in vitro were investigated. In vivo Pb was administered via the drinking water (0 to 10 mM) for 1 to 10 weeks. In vivo exposure of the mice to Pb did not alter significantly their plaque-forming cell response to sheep erythrocytes; however, their susceptibility to Listeria infection was reduced significantly with Pb dosages of greater than 0.4 mM. Although the in vivo plaque-forming cell responses did not appear to be altered, in vitro assessment of the reactivity of these in vivo Pb-exposed lymphocytes indicated that intermediate doses enhanced, but a high dose (10 mM) was suppressive. The 10 mM in vivo Pb dose suppressed the in vitro plaque-forming cell response, the mixed-lymphocyte culture response, and lipopolysaccharide-induced proliferation, but it did not affect concanavalin A- or phytohemagglutinin-induced proliferation. Interestingly, in vitro Pb exposure (10(-6) to 10(-4) M) of murine spleen cells caused an enhancement of most activities even though these in vitro concentrations of Pb were slightly above the in vivo concentrations. Direct in vitro Pb effects on the lymphocytes could be measured, and Pb consistently enhanced humoral and cell-mediated immunity.

Animals↗

Hexose uptake enhancing factor released from Rous sarcoma cells.

Conditioned media from Rous sarcoma virus transformed chicken embryo fibroblasts stimulate the uptake of 2-deoxyglucose in normal chicken fibroblasts. The factor responsible for this effect, which is also shed in very low amount by non-transformed fibroblasts, is destroyed by trypsin and not linked to the protease and plasminogen activator activities present in the media. Its apparent molecular weight, determined by gel filtration, is about 20,000 daltons. The factor released by transformed cells might be related to the monomeric form of a family of glucose binding and transport proteins recently reported by Lee and Lipmann ('78) to be detached by detergents from normal and transformed cells.

Animals↗

Treatment of male hypogonadism with testosterone enanthate.

To determine the relative efficacy of several dosage regimens of testosterone enanthate in the treatment of male hypogonadism, we treated men who had primary hypogonadism with the following dosage regimens: 100 mg once a week, 200 mg every 2 weeks, 300 mg every 3 weeks, and 400 mg every 4 weeks, each for 12--16 weeks. Twenty-three men completed 37 dosage regimens. The 100-, 200-, and 300-mg dosages all suppressed the initially elevated serum LH concentrations to normal, but the 400-mg dosage did not. The 100- and 200-mg regimens suppressed the initially elevated serum FSH concentrations to normal, and the 300-mg regimen almost did not so. All four regimens produced serum testosterone concentrations that fluctuated largely within the normal range, the average concentration between doses was highest with 100 mg and lowest with 400 mg. The regimens of 200 mg every 2 weeks and 300 mg every 3 weeks appeared to be the most effective of those tested in terms of suppression of the serum LH concentration to normal and infrequency of administration. The close parallel of the FSH response to that of LH suggests that testosterone is the major physiological inhibitor of FSH as well as of LH.

Adult↗

Antigenic modulation of the cytophilic binding of guinea-pig IgG and IgM antibodies to homologous macrophages.

The cytophilic binding of immune complexes by peritoneal exudate cells (PEC) from adjuvant-stimulated guinea-pigs was studied using 125I-labelled guinea-pig IgG1, IgG2 and IgM antibodies to the dinitrophenyl (DNP) group. The influence of hapten density upon cytophilic activity was studied by the addition of DNP-conjugated antigens to antibody in 2-200 molar ratios of DNP:antibody. Only IgG2 binding was enhanced by immune complex formation, and the increased binding of IgG2 anti-DNP was dependent on the number of DNP determinants per antigen molecule. Cytophilic activity with epsilon-DNP-L-lysine (DNP-LYS), alpha,epsilon-di-DNP-L-lysine (DNP-LYS-DNP), or DNP1-8-BSA was no greater than that seen in the absence of hapten. Increased cytophilic binding was noted only with DNP20-41-BSA. The binding of IgG2 and IgG2 anti-DNP:DNP-bovine serum albumin (BSA) complexes was inhibited by monomeric IgG2. The relative cytophilic capacities of guinea-pig immunoglobulins appeared as follows: IgG greater than IgG1 greater than IgM. IgG1 and IgM binding of DNP conjugates did not enhance their cytophilic activity; therefore, IgG1 and IgM cytophilic binding to PEC was considered biologically insignificant. This investigation provides further evidence that cytophilic binding of immune complexes to macrophages is due to the co-operative action of multiple Fc sites rather than a conformational change in the IgG2 antibodies, and serum proteins, notably complement components, can alter the binding and/or phagocytosis of IgG2 anti-DNP:DNP-BSA complexes.

Animals↗

A histological comparison of adenomatous and hyperplastic parathyroid glands.

The histological findings in 18 cases of parathyroid hyperplasia associated with chronic renal failure and haemodialysis have been compared with a series of 35 cases of primary adenomatous hyperparathyroidism. Analysis of several features suggests that there are no definite criteria for distinguishing microscopically between individual enlarged glands in primary and secondary hyperparathyroidism, although nuclear pleomorphism is more common in primary adenoma and nodules are more common in secondary hyperplasia. These findings are discussed.

Adenoma↗