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Purpose: To investigate the effect of small doses of radiation on the cell-cycle and related processes, and to determine the capacity of small doses of radiation to induce an adaptive response. Materials and methods: TK6, a lymphoblast cell line with wild-type p53, and U937, a monocytic leukaemia cell line with mutant, inactive, p53 were exposed to gamma ray doses ranging from 0.1Gy to 3Gy. Cell-cycle distributions and cyclin B1 were assessed by flow cytometry, and p53 and p21 protein levels were measured by Western blotting. Apoptosis was determined by fluorescence microscopy after staining with Hoechst 33342, and by measurement of the pre-G1 cell population by flow cytometry. Micronuclei were determined in cytokinesis-blocked cells by fluorescence microscopy. Results: In TK6 cells, radiation exposure induced elevated p53 and p21 levels and delayed expression of cyclin B1. No changes in these parameters were found in U937 cells. Although both cell lines arrested in G2/M after larger doses of radiation, G2/M-arrest occurred after 0.1Gy and 0.3Gy in TK6 cells only. An apoptotic adaptive response was induced in both cell lines by a 0.1Gy priming dose but an adaptive response with respect to micronuclei was observed only in U937 cells. Conclusions: The radiation adaptive response can occur in the absence of wild-type p53. A small dose of radiation may not protect cells against both apoptosis and cytogenetic damage caused by a subsequent larger dose of radiation. [ABSTRACT FROM AUTHOR] more...

Normal rats subjected to end-to-side portacaval shunt showed decreased survival and weight gain, a progressive fall in serum albumin and reciprocal rise in serum gamma globulin when compared with sham-operated controls for 12 weeks. Antibacterial lipopolysaccharide antibody was detected in significant titre at the sixth and twelfth weeks. It is suggested that the elevated levels of gamma globulin and reversal of albumin/globulin ratios noted in these animals may represent an immune response to bacterial lipopolysaccharides released into the systemic circulation as a result of the portacaval shunt. The hyperglobulinaemia of cirrhosis in human subjects may have a similar aetiology. [ABSTRACT FROM PUBLISHER] more...

The kinetics of in vitro cellular proliferation against a PPD of Mycobacterium tuberculosis or streptococcal antigen (streptokinase-streptodornase) was evaluated in pleural fluid and peripheral blood mononuclear cells (PBMC) from patients with tuberculous and non-tuberculous pleuritis. The peak proliferative response to PPD by mononuclear cells from pleural fluid occurred earlier (day 3) in 65% of patients with tuberculosis, a finding not seen in non-tuberculous effusions. Spontaneous lymphocyte proliferation of both peripheral blood lymphocytes and pleural effusion lymphocytes was frequently observed, irrespective of etiology. However, 20 of 21 tuberculous patients manifesting spontaneous lymphocyte proliferation had accelerated kinetics of proliferation to PPD, which was antigen-specific. These results suggest that spontaneous lymphocyte proliferation occurs as a response to antigen stimulation at the site of disease, and is not a non-specific response to inflammation. Furthermore, enhanced reactivity against mycobacterial antigen, manifested by accelerated kinetics of proliferation, has diagnostic potential in patients with pleural effusions. more...

Mycobacterium tuberculosis is a bacterial pathogen capable of survival and replication within human macrophages. Cytotoxic T cells are thought to be important for the eradication of infected macrophages. To test this hypothesis, pleural effusion lymphocytes from patients with tuberculous pleuritis were stimulated in vitro with PPD, and proliferation and cytotoxicity were assessed by thymidine incorporation and chromium release, respectively. The level and kinetics of generation of antigen-specific cytotoxicity were measured and compared with those in autologous peripheral blood, control peripheral blood, and nontuberculous effusions. Both proliferation and cytotoxicity in tuberculous pleural effusions were augmented and accelerated in comparison to autologous or control peripheral blood. By contrast, low levels of cytotoxicity were observed in nontuberculous effusions, without evidence of accelerated kinetics. Cell subset fractionation by panning indicated that the cytotoxicity was mediated by CD4+ cells. The accelerated kinetics of induction of PPD-specific cytotoxic T cells demonstrated here suggests reactivation of in vivo generated cytotoxic T cells. These findings provide evidence that cytotoxic T cells are induced at the site of pathology in vivo and suggest that these cells play an important role in protection in vivo against infection with tuberculosis. more...

The recombinant 65 kDa mycobacterial protein of M. bovis BCG has been shown to be immunodominant in mice immunized with M. tuberculosis. Little is known about reactivity to this antigen in patients with tuberculous pleuritis. In this study therefore, pleural effusion and autologous peripheral blood lymphocytes obtained from patients with tuberculous and nontuberculous pleuritis were stimulated in-vitro with the recombinant 65 kDa antigen. Proliferation was assessed by 3[H] thymidine incorporation. In addition, pleural effusion lymphocytes were activated in vitro with the 65 kDa antigen and tested for cytotoxic activity in 15-hr chromium-release assays. Pleural effusion lymphocytes obtained from a high percentage (56%) of patients with tuberculous pleuritis showed significant proliferative responses to the 65 kDa antigen, while the response in autologous peripheral blood lymphocytes was significantly lower. By contrast, pleural effusion lymphocytes obtained from patients with nontuberculous effusions were not reactive to the 65 kDa antigen. In addition, 65 kDa stimulated pleural effusion lymphocytes obtained from patients with tuberculous effusions showed antigen-specific lysis of autologous targets pulsed with the 65 kDa antigen. These results indicate compartmentalization of the immune response to the 65 kDa antigen and, in addition, provide evidence for in vivo involvement of this antigen in the immune response to M. tuberculosis. more...

The induction of class II antigen (Ag) by interferon-gamma (IFN-gamma) in variants of the K562 cell line has been examined in this study. Following incubation of K562A cells with IFN-gamma, surface expression of HLA-DR molecules was demonstrated by indirect immunofluorescence, confirmed by immunoblotting, and HLA-DR3 Ag specificity identified. HLA-DP and HLA-DRW52 Ag were co-expressed, but no HLA-DQ expression occurred. A variant of this line, designated K1A, spontaneously developed resistance to IFN-gamma induction of class II Ag, but continued to express class I Ag. In a third K562 variant, designated K562B, no class II gene products could be induced. Northern blot analysis indicated that mRNA levels correlated with surface class I and II Ag expression in all of the K562 cell lines. Resistance to IFN-gamma inducible class II Ag expression in K1A cells did not involve changes in IFN-gamma receptor affinity or number but was shown to be due to an inhibitory effect of serum lipid. These results indicate that cells derived from a common parental line may differ in susceptibility to a regulatory mechanism affecting IFN-gamma inducible class II Ag expression. more...

Eight freshly excised pig hearts were hemoperfused by baboons in vivo. Cardiac function ceased in six hearts after a mean period of 90 minutes of perfusion (range 30 to 190 minutes). Two hearts continued functioning for the 4-hour study period. On microscopic examination, seven hearts, including one that continued beating, showed histopathologic features of hyperacute rejection. IgG, IgM, and C3 were strongly present on the myocardium in all cases. Hemoperfusion was associated with significant increases in heart mass (p less than 0.002) and circulating polymorphonuclear leukocytes (p less than 0.03) and reductions in coronary blood flow (p less than 0.0001), circulating lymphocytes (p less than 0.03), and C4 (p less than 0.03). Preformed circulating anti-pig antibodies disappeared in all but one baboon. Hyperacute rejection in this discordant xenograft model that used a nonhuman primate as "recipient" differs in few aspects from that seen in other experimental models. Possible methods of prolonging xenograft survival are discussed. more...

The problem of donor heart supply would be solved if hearts could be transplanted from readily available animals such as the pig or sheep. We have investigated heterotopic heart transplantation (in the neck) with the pig as donor and baboon as recipient. Five experimental groups were studied. Control hearts (group 1, n = 4) were rejected within 4 minutes to 8 hours. Splenectomy done before transplantation (group 2, n = 3) did not extend survival significantly (30 minutes to 8 hours). Donor heart survival in baboons receiving immunosuppressive therapy of cyclosporine and methylprednisolone (group 3, n = 5) was from 15 to 75 minutes only in four animals and for 5 days in one animal. Anti-pig antibody adsorption from baboon blood by pretransplant donor-specific kidney hemoperfusion (group 4, n = 7) resulted in cardiac function for 6 to 12 hours in three cases and from 4 to 5 days in four cases (p less than 0.02). A combination of pretransplant antibody adsorption and immunosuppression (group 5, n = 4) resulted in graft survival of 8 to 20 hours in three cases and of 4 days in one case (p less than 0.03). Histopathologic features of vascular (hyperacute) rejection were seen in all hearts except one (the 5-day survivor in group 3). Pretransplant adsorption of antibody clearly prolonged survival of discordant cardiac xenografts in some cases. Further exploration of this technique appears justified. more...

The population of Southern Africa is currently estimated at least 40 million and comprises people of 3 major--groups Negroid, Khoisan and Caucasoid. In addition to these, there are also smaller groups whose origin is Asiatic or Oriental, and a mixed group (coloured) which has resulted from the miscegenation between the Negroid-Caucasoid and other groups [1]. This great diversity of peoples and cultures permits unique opportunities for studies in comparative medicine which may provide valuable information about the pathogenesis and natural history of disease. The rheumatic diseases have not been looked at in this comparative way until recently. This is, in part, because the demands of infective and nutritional diseases on medical services have tended to overshadow the rheumatic diseases. This paper reviews the investigation of inflammatory rheumatic disease in Southern Africa. more...

This study was designed to investigate further the hyperglobulinaemia which followed portal or splenic venous diversion but not mesenteric venous diversion. It was observed that levels of IgG and IgM were elevated from 3-6 weeks after portacaval shunt, portacaval transposition or splenacaval shunt. IgA levels were increased after all forms of portal venous diversions including after mesentericocaval shunt. The failure of levels of IgG and IgM to rise after mesocaval shunting suggests that some component of splenic venous blood may regulate the ability of the reticulo-endothelial system of the liver to respond to antigenic influences. more...

The effect of sodium salicylate on peripheral blood leucocyte migration is described. At a concentration of 3,5 mmol/ml, no effect on leucocyte migration was seen, but this concentration appears to influence the leucocyte migration in the presence of specific antigen, either by increasing or by decreasing leucocyte migration inhibition. more...

In previous studies of rats with portacaval shunts, elevated gamma-globulin levels 2 weeks after shunt were attributed to antibodies to bacterial lipopolysaccharide, which were normally filtered by the liver. This study was designed to determine the tempo of this rise and the magnitude of hepatocellular damage within the first 4 days of the operation. Acute reversible hepatocellular damage was shown by elevated levels of aspartate aminotransferase which returned to normal within 48 hours. This was confirmed on histology. There was no rise in gamma-globulin during this study but levels of albumin were better maintained in shunted rats than in sham-operated rats. Levels of alpha2 and beta-globulin in the former fell in comparison with the latter animals. more...