IL-4 inhibits human CD8 T cell expression of the common IL-2 receptor gamma chain

Previous studies in both rats and humans have shown that interleukin (IL) 4 can suppress the generation of IL-2-producing CD8 T cells. In an attempt to elucidate the mechanism by which this suppression is brought about, we set out to investigate whether the IL-4 signal interferes with the IL-2 receptor system. It has already been reported that IL-2 can affect the expression of its own receptor and thus provide a means of controlling its own activities. In this study, we demonstrate that the IL-2 Ralpha- and the IL-2 Rgamma-chains are dramatically upregulated following stimulation of CD8 T cells, whereas lower levels of beta-chain are observed. IL-4 did not affect the expression of the alpha- or beta-chains, but was found to inhibit the generation of common gamma-chain-expressing cells. Moreover, CD4 T cells were found to express much lower levels of this subunit and appeared less sensitive to the effects of IL-4. We postulate that the differential expression of the gamma-chain subunit, in the presence and absence of IL-4, may provide a tool for identifying functionally distinct subpopulations of CD8 T cells.     

Evaluation of screened blood donations for human immunodeficiency virus type 1 infection by culture and DNA amplification of pooled cells

BACKGROUND. Reports of transmission of the human immunodeficiency virus type 1 (HIV-1) from transfusions of screened blood and reports of silent, antibody-negative HIV-1 infections in persons at high risk continue to foster concern about the safety of the blood supply. Previous estimates of the risk of HIV-1 range from 1 in 38,000 to 1 in 300,000 per unit of blood but are based on either epidemiologic models or the demonstration of seroconversion in recipients. METHODS. We isolated peripheral-blood mononuclear cells from blood that was fully screened and found to be seronegative, combined them into pools of cells from 50 donors, and tested them for HIV-1 by viral culture and the polymerase chain reaction, using protocols specifically adapted for this analysis. RESULTS. The 1530 pools of mononuclear cells were prepared from 76,500 blood donations made in San Francisco between November 1987 and December 1989. Of these pools, 1436 (representing 71,800 donations) were cultured successfully; 873 (43,650 donations) were evaluated by the polymerase chain reaction. Only one pool was confirmed as HIV-1--infected by both methods. After adjustment for sample-based estimates of the sensitivity of the detection systems using culture and the polymerase chain reaction, the probability that a screened donor will be positive for HIV-1 was estimated as 1 in 61,171 (95 percent upper confidence bound, 1 in 10,695). CONCLUSIONS. Silent HIV-1 infections are exceedingly rare among screened blood donors, so the current risk of HIV-1 transmission from blood transfusions, even in high-prevalence metropolitan areas, is extremely low.     

Interactions between polymerized human albumin,hepatitis B surface antigen,and complement: II. involvement of Clq in or near the hepatitis B surface antigen receptor for polyalbumin

A species-specific receptor for polymerized human albumin (PHALB) has been reported on hepatitis B surface antigen (HBsAg)-carrying particles. Our previous observations that human Clq also binds PHALB in a species-restricted manner led us to investigate the possibility that HBsAg-associated Clq is involved in the PHALB receptor on HBsAg particles. The temperature, ionic strength, and pH requirements necessary for binding of PHALB to both Clq and HBsAg were compared and found to be similar. Normal human serum and purified Clq inhibited the PHABL-HBsAg interaction; the inhibition was markedly reduced in heat-inactivated and Clq-depleted serum. Heat-denatured or reduced and alky-lated Clq failed to inhibit the PHALB-HBsAg binding. Moreover, human Clq was found to be present in purified preparations of HBsAg and the quantity detected paralleled the degree of PHALB-HBsAg binding. While anti-Clq inhibited the PHALB-HBsAg interaction, anti-Clr, -Cls, -C3, and -Ig were not inhibitory. Collagenase treatment of purified HBsAg reduced both PHALB-binding activity and the degree of HBsAg-associated Clq. These observations provide evidence that HBsAg-associated Clq is involved in or near the HBsAg-binding site for PHALB.     

Novel predictive risk factor for Erectile Dysfunction: Serum folic acid

The purpose of this study was to compare the serum Folic Acid (FA) levels in patients with Erectile Dysfunction (ED) and healthy controls and whether levels vary with its severity. The study was carried out on 77 sexually active individuals, out of which 41 complained of ED and 36 were apparently normal. Patients were excluded if they had any diseases known to cause ED. The severity was further categorised based on IIEF-5 scores. Blood serum levels of testosterone, lipid profile, random blood sugar, liver function test, renal function test and FA levels were obtained in each patient. Independent-samples t test of significance was used when comparing between two means. Pearson's correlation coefficient (r) test was used for correlating data. All clinical and biochemical parameters except FA were comparable in both the groups. FA levels were significantly decreased in ED group (5.29 vs. 10.8; p value = .004). Smoking habits were comparable between the groups, and FA levels did not vary among smokers and nonsmokers (p value = .46). Serum FA levels significantly declined with increasing severity of ED (8.28 vs. 5.56 vs. 4.37 vs. 3.5; p value < .001). Thus, decreased FA might possibly be one of the novel risk factors for ED.     

Biotransformation of lovastatin--III. Effect of cimetidine and famotidine on in vitro metabolism of lovastatin by rat and human liver microsomes

The effects of the H2-receptor antagonists, cimetidine and famotidine, on the microsomal metabolism of [14C]lovastatin were investigated. Liver microsomes were prepared from control, phenobarbital- and 3-methylcholanthrene-pretreated rats and humans (male and female). Concentration-dependent inhibition of the metabolism of lovastatin (0.1 mM) was observed with cimetidine (0.1 to 1.0 mM). In contrast, famotidine at a similar concentration was a very weak inhibitor. The formation of 6'beta-hydroxy-lovastatin, the major microsomal metabolite of lovastatin, was similarly inhibited. The results suggest that in vivo metabolic interaction with concomitantly administered lovastatin is less likely with famotidine than with cimetidine. Phenobarbital pretreatment produced 58% stimulation in overall metabolism, whereas 3-methylcholanthrene pretreatment had no effect relative to control rats (5.4 nmol/mg protein/min). Liver microsomes from phenobarbital-pretreated rats produced 67% more of the 6'beta-hydroxy-lovastatin but 63-66% less of the 3'-hydroxy and 6'-exomethylene metabolites. Liver microsomes from 3-methylcholanthrene-treated rats also produced less 3"-hydroxy-lovastatin (49%) but similar quantities of the other two metabolites. 6'beta-Hydroxy-lovastatin was a major metabolite with human liver microsomes. Interestingly with these microsomes, hydroxylation at the 3'-position of the molecule was a negligible pathway and hydrolysis to the hydroxy acid form was not observed. The formation of 6'-exomethylene-lovastatin was also catalyzed by human liver microsomes (0.5 to 0.8 nmol/mg protein/min).