Biomedical subjects
Publications and source records attributed to G Maier.
Fifty-three black patients with acute nongranulomatous anterior uveitis (AAU) were tissue typed and the results compared to those from a panel of 200 healthy unrelated black volunteers. No statistically significant deviation from the norm with regard to the frequencies of 38 HLA antigens could be observed.
Forty-five white patients (32 with open-angle glaucoma and 13 with ocular hypertension) and 63 black patients (41 with open-angle glaucoma and 22 with ocular hypertension) were tissue typed for a total of 38 HLA antigens and the results compared to normal, unrelated, panels of 248 white donors and 150 black volunteers, respectively. No statistically significant differences with regard to the frequencies of 38 HLA antigens were detected among the various groups.
Although hepatocellular carcinoma is probably caused by one or more environmental carcinogens, a genetically determined susceptibility to the development of the tumor has not been excluded. In looking for such a predisposition, we have compared the histocompatibility antigens (HLA) of 102 southern African blacks with histologically proved HCC with those of 208 healthy blacks. The standard two-stage lymphocyte microcytotoxicity method was used to test for 40 antigens: 17 in the A locus, 20 in the B locus, and 3 in the C locus. None of the HLA antigens had a frequency that was significantly different in the patients and the controls. A close association undoubtedly exists between chronic hepatitis B virus infection and hepatocellular carcinoma. If this virus is proved to be oncogenic with respect to hepatocellular carcinoma, a genetic predisposition to the hepatitis B virus carrier state may have an indirect bearing on the etiology of the tumor. Sera from the hepatocellular carcinoma patients were therefore tested for hepatitis B virus markers (HBV surface antigen and antibody against HBV core antigen), and these were related to the patients' histocompatibility antigens. None of the HLA antigen frequencies was significantly different in the surface antigen-positive and the surface antigen-negative patients. As 88% of the patients were anticore positive, no meaningful correlation could be carried out with this marker. Analysis of histocompatibility antigens thus failed to show evidence of a genetic predisposition either to hepatocellular carcinoma or to chronic hepatitis B surface antigenemia in patients with this tumor.
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Techniques for sizing radiocolloids are reviewed. The small size range (1-100 nm) of many radiocolloids and their polydispersity limit the choice of the technique used. To compare several techniques directly, the particle size of Technetium-99m sulfide colloid was studied using Nuclepore filtration, ultracentrifugation and electron microscopy. The last of these was adopted as the method of choice. Using this technique, the particle size and shape of colloids below 100 nm can be accurately determined. Technetium-99m antimony sulfide colloid and indium-113m hydroxide were then examined by electron microscopy, and the chemical nature of the particles was determined by x-ray fluorescence analysis. Results resolved the size discrepancies reported in the literature and demonstrated the importance of identifying the chemical nature of the particles under examination.
Assays of cell-mediated immunity before transplantation were performed on 34 patients who were defined as being at high risk by the presence of preformed lymphocytotoxic antibodies and/or HL-A incompatibilities at FOUR locus. Assays for cell-mediated lympholysis type I (cml I) were performed in donor serum, and for CML II in recipient serum, to assess the possible effect of blocking factors in the patients' sera. A positive (greater than 5% specific Cr release) and in particular a greater than 10% Cr release correlated strongly with graft rejection. The correlation between CML II and graft survival was unimpressive. No clinically beneficial blocking factor was demonstrable in the patients's sera in that 5 of 6 patients with a positive CML I but a negative CML II rejected their grafts. Conversely, 6 of 8 patients with a positive CML II and a negative CML I had excellent long-term courses. The use of CML I assay in the selection of grafts for patients at high risk is recommended.
The role of HL-A matching in the clinical outcome of 159 consecutive first cadaver renal allografts at the Johannesburg General Hospital has been analysed over a 7-year period, April 1968-May 1975. Over-all actuarial graft survival was 69% at 1 year and 57% at 7 years. When all cases were considered together there was a trend towards improved graft survival with better grades of matching, but this was not statistically significant. Presensitisation had an adverse effect on graft survival. Donor-recipient combinations with no demonstrable FOUR locus mismatches provided a significantly superior graft survival rate of 82% 1-6 years after transplantation. The majority of these compatible for HL-A 7, 8 OR 12, and therefore may have been matched indirectly for lymphocyte activating determinants. Relatively inferior graft survival was observed with FOUR locus incompatibility in patients who had been presensitised, and when donor-recipient combinations had no serologically determined antigens in common, particularly in the donor "full house" situation. Despite these unfavourable immunogenetic circumstances, approximately 50% of grafts functioned well for long periods, and not infrequently clinical considerations took precedence over immunological considerations in the selection of recipients. This policy is justified by over-all results, the critical shortage of cadaver organs in relation to clinical requirements and the rare occurrence of combinations with superior HL-A matching. Specific allograft tolerance remains the goal of clinical organ transplantation.
The dependence of integration of newly formed DNA chain ( less than 10 S) into larger DNA on concomitant protein synthesis was studied in a special cellular system. Exponentially growing Ehrlich ascites tumor cells in vivo show decreasing rated and finally complete cessation of protein and DNA synthesis upon transfer into an isotonic but non-nutritive environment (Hanks' balanced salt solution). Both protein and DNA synthesis is stimulated in these cells for a period of 30 min when they are placed into fresh Hanks' balanced salt solution; however, stimulation of protein synthesis is completely prevented in Hanks' balanced salt solution containing cycloheximide. This system allowed us to investigate the formation and fate of newly formed DNA chains ( less than 10 S) in dependence of protein synthesis. Analysis of DNA produced in [3H]thymidine pulses showed that DNA chains smaller than 18 S were still formed during the phase of totally delayed protein synthesis and in the presence of cycloheximide, but they were not converted into DNA molecules sedimenting faster than 18 S under these conditions. Stimulation of protein synthesis for a period of 30 min allowed the short DNA pieces to be chased into larger DNA 30 min post stimulation of protein synthesis. The results clearly indicate that DNA chain growth, by sealing of DNA chains smaller than 18 S, is strongly dependent of concomitant protein synthesis. Direct chain elongation by addition of new deoxyribonucleotides is less dependent on concomitant cellular protein synthesis.
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Hepatitis B virus (HBV) markers were measured in 83 immunosuppressed renal transplant patients who were followed for periods of 2 to 15 years. Sixty-nine patients were negative for HBsAg before transplantation, of whom 14 were positive for anti-HBs. The remaining 14 patients were HBsAg positive prior to transplantation. Eighteen patients were identified as being HBsAg positive during the follow-up period. Four patients acquired primary type B hepatitis; one died of submassive hepatic necrosis and the remaining three became chronic HBV carriers with positive HBeAg, DNA polymerase, and HBV DNA. Several patterns of HBV expression were observed in HBsAg-positive patients. Four patients were HBsAg, HBeAg, DNA polymerase, and HBV DNA positive prior to transplantation, and these markers persisted. Reactivation of HBV replication occurred in eight patients, seven of whom were HBsAg positive and HBeAg and anti-HBe negative originally; one patient was anti-HBc positive. A single patient was HBsAg and anti-HBe positive and remained so for 22 months. The remaining previously HBsAg-positive patient is currently HBsAg negative. These serological data suggest that reactivation of HBV replication or continued hepatitis B virion replication occurs as commonly or more commonly than de novo infection in renal transplant recipients. The presence of HBeAg in serum predisposes to long-term Dane particle expression in immunosuppressed patients, whereas anti-HBe-positive carriers may not always be susceptible to reactivation of HBV replication despite immunosuppression.
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