Quantitative analysis of contrasuppressor T lymphocytes in leprosy; induction of Ia antigens with gamma interferon

Lepromatous leprosy is characterized by immune anergy and abnormal suppressor T-cell function. Contrasuppressor cells are a subset of CD8+, vicia villosa-adherent T lymphocytes. T-contrasuppressor (Tcs) cells act on T-helper cells to cause them to become unresponsive to the action of T-suppressor cells. In 8 lepromatous (LL) and 7 tuberculoid (TT) patients, and 6 healthy contacts we studied the percent of the following lymphocyte subsets: CD3+, CD4+, CD8+, Ia+, vicia villosa+ (VV+), CD8, VV+, VV, Ia+, and Ia, Tac+. This was done in baseline status as well as post-stimulation with recombinant gamma interferon (rIFN-gamma). We found that peripheral blood mononuclear cells from LL and TT patients and controls exhibit a similar number of putative contrasuppressor lymphocytes (CD8, VV+ cells). However, in the contrasuppressor subset from LL patients we found a low percent of Ia+ (p less than 0.05 compared to controls or TT). In the three groups studied, the rIFN-gamma enhanced the percent of Ia+ lymphocytes in the CD8, VV+ cell subpopulation. However, the CD8, VV+ lymphocytes from LL patients, despite the effect of rIFN-gamma, continue to have a low percent of Ia+ cells (p less than 0.05 compared to controls or TT). These findings suggest that LL patients might have abnormalities in the contrasuppressor immune circuit. Future functional studies on the role of Tcs cells in the anergy seen in LL will be required in order to define the apparent dysfunction occurring in this disease.     

Hydrophobic surfactant effects on aortic cholesterol accumulation and atherosclerosis in hypercholesterolemic rabbits

Studies were performed in hypercholesterolemic rabbits to determine whether the hydrophobic surfactant, Poloxalene 2930 (Pol), is of benefit under these conditions. Lipoprotein analyses plus chemical and morphologic studies of the aorta were performed to evaluate the results. In one study, rabbits were made hypercholesterolemic by dietary means and then divided into two groups and given a cholesterol-free diet with one group additionally given Pol with treatment continued for 10 weeks. Pol treatment resulted in less atherosclerosis but the mechanism for this effect was not apparent from lipoprotein analysis. In the other study 3 groups of rabbits were given a cholesterol-rich diet for 16 weeks. Two groups received Pol supplement with one of these groups receiving a dose that was too small to prevent hypercholesterolemia. In this group plus the group on diet alone comparable degrees of hypercholesterolemia were maintained throughout the study. Lipoprotein abnormalities were similar in these two groups except that those on Pol had a more normal cholesterol to apolipoprotein B ratio. The amount of atherosclerosis in both groups was mild but aortic cholesterol content was much less for the Pol group. It is concluded that Pol limits cholesterol accumulation in the aortic wall of hypercholesterolemic rabbits and can retard the development of atherosclerosis.     

Biochemical effects of two promoters of hepatocarcinogenesis in rats

The effects of two promoters of hepatocarcinogenesis--phenobarbital and butylated hydroxytoluene (BHT)--on five hepatic biochemical parameters were examined in adult female rats. Phenobarbital given orally in two doses each of 110 mg/kg 21 and 4 hr before the rats were killed caused large increases in hepatic ornithine decarboxylase (ODC) activity and cytochrome P-450 content. Extending the number of phenobarbital treatments to five increased the hepatic enzyme induction and also caused a minor decrease in hepatic glutathione and a small increase in serum alanine aminotransferase activity. Two oral doses of 700 mg BHT/kg (20% of the LD50) caused hepatic DNA damage and induction of both ODC activity and cytochrome P-450 content. When the dose of BHT was reduced from 700 to 140 mg/kg no significant effects on the biochemical parameters were found. Both promoters of hepatocarcinogenesis were identified by their induction of ODC, a marker for promotional potential, but only BHT showed a potential for carcinogenic initiation. The biochemical parameters examined, particularly the alkaline elution technique for DNA damage, ornithine decarboxylase activity and serum alanine aminotransferase, may constitute a useful assay system for examining a compound's potential for carcinogenic initiation, carcinogenic promotion and cellular toxicity.     

Teaching behavioral medicine using individual coronary heart disease risk factors

Two hundred twenty-one first-year medical students participated in a voluntary coronary heart disease risk factor self-change project designed to teach the principles of behavioral change. Blood pressure, serum lipids, percentage body fat, cardiovascular fitness, and smoking status were measured prior to the project. Students designed their own programs of behavior modification and, after 8 weeks, repeat measurements were obtained in students whose projects related to coronary heart disease risk (56% of entire group). Despite generally low initial coronary heart disease risk factors, most risk factor groups successfully altered the targeted risk factors. The subgroup attempting to lower serum cholesterol (n = 49) reduced total cholesterol 15 +/- 24 mg/dl (mean +/- SD) and low-density lipoprotein cholesterol 11 +/- 20 mg/dl (P less than 0.001 for both). The blood pressure group (n = 9) decreased systolic blood pressure 8 +/- 10 mm Hg (P less than 0.05), and the weight-loss group (n = 33) lost 3.0 +/- 2.9 kg (P less than 0.001), reducing estimated percentage body fat 1.7 +/- 1.8 (P less than 0.001). The self-change project was well received by the students and appears to be a useful technique for introducing the principles of behavioral medicine to first-year medical students.     

Effect of chronic administration of different Bence Jones proteins on rat kidney

The role of Bence Jones proteins (BJPs) in the genesis of the renal dysfunction that develops in patients with multiple myeloma is not clearly defined. We previously evaluated renal function and morphology in a unique strain of rats (LOU/m) bearing tumors which synthesized BJPs with isoelectric points of 5.2, 4.3 and 6.7. Myeloma cast nephropathy developed in one tumor bearing group (pI 5.2), tubular necrosis was observed in another (pI 4.3), and renal function and histology remained normal in a third group (pI 6.7). To see if these renal outcomes were a function of the BJP being excreted or other factors which could be present in the tumor bearing animals, we have examined the effect of chronic intravenous administration of these three BJPs on renal function and histology in non-tumor-bearing LOU/m rats. Urine containing the BJP was collected from tumor bearing rats, sterilized by passage through a 0.2 mu millipore filter, concentrated to 50 mg/ml, and dialyzed extensively so as to remove material with a molecular weight less than 3500. Chronic indwelling-venous catheters were placed in non-tumor-bearing LOU/m rats and these rats were given 100 mg/day for five days of one of the three BJPs. Polyfructosan clearance (Cin) was measured prior to and following the five days of BJP administration. Renal histology was examined at the completion of the second Cin. In the pI 5.2 group (N = 6), a severe distal nephron cast nephropathy occurred and Cin fell from 2.88 +/- 0.24 to 0.90 +/- 0.17 ml/min (P less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)