Diabetes mellitus is a genetically determined disorder of metabolism in which inherited susceptibility plays an important part. We studied the distribution of HL-A antigens, and theincidence of lymphocytotoxic and tissue antibodies in seventy-one adult diabetic patients—fifty insulin-dependent and twenty-one insulin-independent. Specificity W15 was present in significantlyhigher frequency in the insulin-dependent diabetic patients than either in the control group (P = 0.0005) or in the insulin-independent diabetic patient group (P < 0.0005). The incidence of lymphocytotoxic and tissue antibodies in the two patient groups was not different from that in the control population.

The hypothesis that lymphocytotoxic antibodies are associated with neuropsychiatric involvement in systemic lupus erythematosus (NP-SLE) is re-evaluated in this study. In

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with HLA-DR genes that share amino acid sequence motif QKRAA/QRRAA from position 70 to 74 in the third hypervariable region of DR1 molecule. The contribution of HLA in RA is however about 37%, suggesting a role for other genes. One such candidate is the gene that encodes natural resistance-associated macrophage protein (NRAMP1), which plays a crucial role in inflammation and tissue destruction. In the present study, we examined the role of NRAMP1 gene polymorphisms in susceptibility to RA. The results show that variation at position 543 in exon 15, which involves substitution of negatively charged aspartic acid (D) by uncharged asparagine (N), and the deletion of TGTG in the 3' UTR may confer protection from development of RA.

SummaryWe have previously shown that repeated or continuous intimal injury caused by an indwelling aortic catheter causes a variety of lesions in rabbits maintained on a diet unsupplemented by lipid. These include fatty streaks, lipid-free fibrous plaques and lipid-rich raised thromboatherosclerotic plaques. Whether lipid-rich raised lesions are a result of injury or co-existing thrombosis or both is not clear. The present experiment was designed to answer this question. Anti-platelet serum (APS) to washed sonicated rabbit platelets was raised in sheep. PE 60 polyethylene catheters were placed in the aortas of 35 rabbits by way of a femoral artery. The animals were randomly divided into 2 groups. The experimental group (17 rabbits) received an intravascular injection of 1.0 ml of APS followed 8 hours later by a subcutaneous injection of 0.5 ml. Thereafter, 0.5 ml APS was given subcutaneously each day for 13 additional days. The control group (18 rabbits) received no APS. Platelet counts were done prior to surgery, at 5 minutes following surgery, at 4 days, 8 days and just prior to killing. Extent of lesions was estimated by photographing the opened aortas, projecting the photographs on cardboard, cutting out the areas occupied by the different lesions and weighing the cardboard. The mean weight of raised lesions in the control group was 6 to 7 times greater than in the experimental groups. Statistical analysis of this difference based on Welsh‘s “t” test for unequal variances was highly significant (P<0.001). Platelet counts in the experimental group varied from 0 to 20,000 at 14 days. In animals with platelet counts ≤ 1,000 mm3 raised lesions were completely prevented. In a second experiment the effect of APS was compared with normal sheep serum (NSS). A similarly significant inhibition of raised lesions occurred in the APS group. The extent of lesions in the NSS control was similar to that in the No-APS group of the first experiment. These findings indicate that thrombosis is more important than injury in the development of lipid-rich raised lesions.

Allogeneic blood transfusions have been reported to induce immunomodulation in recipients of blood products. While the mechanism(s) of this immunomodulatory effect is unknown, it has been suggested that this effect of allogeneic blood transfusions could adversely affect patients with a malignant disorder. These concerns have been supported by a number of nonrandomized, mainly retrospective, clinical studies which indicate that allogeneic blood transfusions can adversely affect prognosis following the surgical treatment of oncology patients. Recently, we have shown that allogeneic blood transfusions enhance primary tumor growth and increase metastatic pulmonary nodule formation in inbred mice. The tumor growth-promoting activity of allogeneic blood transfusions was studied also using outbred rabbits. In this present study, we demonstrate that the tumor growth-promoting effect of allogeneic blood transfusions is mediated by donor leukocytes and that this effect can be abolished by their removal before transfusion. We show also that the allogeneic blood transfusion tumor growth-promoting effect can be passively transferred to naive animals (both mice and rabbits) using spleen cells from allogeneically transfused animals. In these experiments, numbers of metastatic pulmonary nodules were significantly increased in both mice and rabbits that had received spleen cells from allogeneically transfused animals compared with those that had received spleen cells from syngeneically transfused animals, or from animals that had been transfused with leukodepleted allogeneic blood.

We have studied TAP polymorphism in a panel of 40 healthy individuals, 57 patients with pulmonary tuberculosis (PTB) and 50 with tuberculoid (TT) leprosy from North India. Only TAP2-A/F occurred with a significantly increased frequency in PTB patients as compared to controls (82.5% vs. 52.5%, P < 0.002, Pc < 0.01) giving a high relative risk of 4.3. On the other hand, TAP2-B was significantly increased in TT leprosy as compared to controls (76% vs. 47.5%, Pc < 0.003, RR 3.5) particularly in patients positive for HLA-DR15 than controls carrying DR15 (77.5% vs. 50%, P < 0.03, RR = 3.4). Further, TAP2-B allele was positively associated with DR15 negative PTB patients as compared to the DR15 positive group (43.8% vs. 17.1%, P < 0.04, RR = 0.3). This study along with our earlier studies on HLA association in mycobacterial diseases suggests that in addition to HLA-DR15 alleles in the TAP2 region influence susceptibility to PTB and TT leprosy.

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