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Biomedical subjects

M Macleod

Publications and source records attributed to M Macleod.

At least 19 recordsLinked to original sources

DNA analysis of HLA-DR, DQ and DP genes in pauciarticular juvenile rheumatoid arthritis.

HLA-DR, DQ, and DP alleles were determined by restriction fragment length polymorphism (RFLP) and oligonucleotide hybridization analysis in 50 Caucasian children with pauciarticular juvenile rheumatoid arthritis (PaJRA) and 82 controls. There was an increased frequency of DR5, DRw8, and DQw4, as well as individual DQ alpha and beta chains, DQA*0401 and DQB1*0402, respectively, in this group of patients. There was an absolute association between DRw8, DQw4, DQA1*0401, and DQB1*0402 in the patient population. HLA-DPw2.1 was also increased in frequency. There was little evidence of linkage disequilibrium found between DPw2.1 and DR5, DRw8, or DQw4. These MHC Class II associations were more characteristic of those patients with young age of onset (less than 5 years), rather than those with onset greater than or equal to 5 years of age. Our data confirmed the previous associations of HLA-DR5, DRw8, and DPw2.1 with PaJRA and suggested a new association for DQ alpha and beta genes in the clinical expression of this disease.

Alleles

Accelerated atherosclerosis in long-term dialysis and renal-transplant patients: fact or fiction?

The causes of death and morbidity in a series of 104 patients with end-stage renal disease were analysed in an attempt to determine whether dialysis and renal transplantation accelerate atherogenesis. Only 4 of 37 deaths were due to myocardial infarction; a further 2 were due to other manifestations of occlusive arterial disease; and severe atheroma was an incidental finding at necropsy in only 3 other patients. Symptomatic arterial disease developed during treatment in only 3 of 61 patients at present alive; 2 other patients with myocardial infarctions before dialysis treatment have survived uneventfully for long periods. These data suggest that dialysis and transplantation may allow previously acquired atherosclerosis to manifest itself clinically; but the hypothesis that atheroma is accelerated is not yet proven.

Adolescent

Critical importance of microsome concentration in mutagenesis assay with V79 Chinese hamster cells.

For optimum mutagensis in V79 Chinese hamster cells, the amount of liver postmitochondrial fraction in the assay was found to be of critical importance, depending on the chemicals being tested. Benzo[a]pyrene (BP) required lower (1-5%) concentrations of the liver 15 000 X g supernatant (S15) from methylcholanthrene pretreated rats for a maximum induction of cytotoxicity and mutagenicity, as determined by 8-azaguanine- and ouabain-resistance. A sharp peak of mutagenicity and cytotoxicity was induced by 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-diol BP) at a concentration of 1% of the S15 fraction. Little or no response was induced by these compounds with the S15 concentrations of more than 10%. Similarly, aflatoxin B1 induced a sharp peak of mutagenicity and cytotoxicity at a concentration of 2% of the liver S15 fraction from Aroclor-pretreated rats. Under the same condition, non-carcinogenic aflatoxin G2 did not induce cytotoxicity and mutagenicity. Analysis of BP metabolites by high-pressure liquid chromatography indicates that with the 30% S15 fraction, more than 80% of BP was metabolized during the first 15 min, while with the 2% S15 fraction, 7,8-diol BP increased continuously throughout the 120-min incubation period, suggesting a strong metabolic competition to rapidly remove BP and 7,8-diol BP with a high concentration of the S15. In contrast with these compounds, N-nitrosodimethylamine induced mutagenicity and cytotoxicity which increased linearly in proportion to the increasing amount of the S15 fraction from phenobarbitone- and Aroclor-pretreated rats. Various nitrosamines with different lipophilicity were examined at a high (30%) and low (2%) concentration of the S15 fraction from Aroclor-pretreated rats, in which ratios of mutation frequencies at 30% and 2% correlated inversely with lipophilicity of the compound. This result suggests that the lipid solubility of test compounds may be one factor which determines the concentration of post-mitochondrial supernatant for optimum mutagenesis.

Aflatoxins

Clinical and laboratory studies of levamisole in patients with rheumatoid arthritis.

Two studies with levamisole in rheumatoid arthritis are reported. In the first study of 30 patients levamisole was superior to placebo in terms of pain relief, reduction in articular tenderness, duration of morning stiffness, erythrocyte sedimentation rate (ESR), and radioisotope uptake in knee and wrist joints. There were no consistent differences in lymphocyte function, immunoglobin or complement concentration, or polymorphonuclear granulocytic function. In the second study forty patients were commenced on treatment with either gold or levamisole. At the end of one year there were significant improvements with both regimens in pain score, joint tenderness and ESR. The patients on levamisole showed significant improvement of duration of morning stiffness, while the patients on gold showed significant improvement of rheumatoid factor titre and left hand grip, but there were no significant differences between the two regimens.

Adult

Maintenance of silastic-teflon shunts for intermitten haemodialysis.

The occurrence of infection in the tissues surrounding external arteriovenous shunts was studied and die important relationship of pyogenic infection to clotting was confirmed. The local application of fusidic add tulle and lanolin greatly reduced the occurrence of both infection and clotting and the need for cannula replacement.Urokinase used for declotting shunts when standard procedures had failed, restored blood flow whether dotting was related to infection or to local vascular factors. This treatment is not advised when clotting is associated with a local abscess, as it may make cannula replacement necessary. Severe local vascular factors, such as metastatic calcification, Raynaud's phenomenon, and venous stenosis, may lead to poor blood flow, so that despite clot lysis elective cannula replacement or the creation of a subcutaneous arteriovenous fistula is required.

Abscess