Immunologic effects of interleukin 2 in primary immunodeficiency diseases

Five children with primary deficiencies of T cell function were studied to assess the effects of highly purified exogenous Interleukin 2 (IL 2) on their in vitro T cell responses. The lymphocytes from one child with Nezelof's T cell deficiency demonstrated absence of endogenous IL 2 production and improved proliferative responses to mitogen or alloantigen in the presence of exogenous IL 2. Moreover, during in vitro mixed lymphocyte culture in the presence of exogenous IL 2, his lymphocytes were able to develop into cytotoxic effector cells. A second child with Nezelof's syndrome demonstrated a different type of defect. The lymphocytes from this child had less impairment of endogenous IL 2 production. Although IL 2 increased the proliferation of his cells in response to PHA, similar augmentation was not seen after stimulation with OKT3 or alloantigen. In cell-mediated cytotoxicity assays, after mixed lymphocyte culture, natural killer-like activity was strongly boosted in the cultures that contained IL 2, but T cell-mediated cytotoxicity was not. The lymphocytes from three patients with severe combined immunodeficiency did not show improved proliferative responses in the presence of IL 2. Thus, only one of the five patients demonstrated the combination of defective endogenous IL 2 production, but preservation of the ability to respond appropriately to exogenous IL 2. This child may therefore have suffered from a T cell defect pathophysiologically similar to that seen in nude or aged mice.     

Binding of the transition metal ion [(H20)(NH3)5Ru(II)]2+ to nucleosomal core and internucleosomal DNA

The goal of this study is to establish the nature of pentammineruthenium(III) binding to DNA in intact mouse liver nuclei. Also, we wish to determine whether the nucleosomal organization of mouse chromatin has a substantial effect on the relative Ru(III) binding levels of internucleosomal and nucleosomal core DNA. These questions are important because ammineruthenium compounds share chemical and biological properties with the cis-dichlorodiammineplatinum(II) or cisplatin chemotherapeutic agent. Therefore, they represent a potential class of new chemotherapeutic agents. We find that in intact nuclei the predominant DNA binding site for pentammineruthenium(II), followed by air oxidation to pentammineruthenium(III), is N-7 guanine, as is the case with cisplatin. Also, the Ru(III) distribution between internucleosomal and nucleosomal core DNA was found to be nearly identical as probed with three non-specific deoxyribonucleases.     

The influence of fish oil supplementation on plasma lipoproteins and arterial lipids in vervet monkeys with established atherosclerosis.

There is controversy about whether supplementing diets with marine fish oil can regress, promote or prevent atherosclerosis. Therefore the effects of an Atlantic pilchard oil (FO) supplement and dietary change were measured in a proven atherosclerosis model. Vervet or African Green monkeys were fed an atherogenic diet (AD) for long enough to ensure progression before treatments started. Matched groups were then treated for 20 months, either by adding FO to the AD (AD/FO), or by changing to a therapeutic diet with FO (TD/FO). Control treatments consisted of supplementing with sunflower oil (SO) instead of FO, so that treatments were AD/SO and TD/SO. The same total polyunsaturates were supplied by the FO and SO and the dose of FO was realistic (2.5% of total energy). A reference group (R) received the TD with no oil supplements. Supplementing with FO did not change the concentrations of total, low or high density lipoprotein cholesterol in plasma. After The AD/FO the intimas of aortas contained more total (p < or = 0.001), free (p < or = 0.05) and esterified (p < or = 0.05) cholesterol, total phospholipid (p < or = 0.01) and sphingomyelin (p < or = 0.05) than after the AD/SO. After FO supplementation eicosapentaenoic acid was significantly higher and arachidonic acid significantly lower in the plasma and aorta intima phosphatidylcholine. None of these changes was anti-atherogenic in terms of atherosclerosis measured in the same individuals (1). Nor did FO increase the efficacy of the TD.     

Effect of beta-adrenoceptor blockade on thermoregulation during prolonged exercise

The effect of clinically used equipotent doses of nonselective (beta 1/beta 2; propranolol) and selective (beta 1; atenolol) beta-adrenoceptor blockers on thermoregulation was studied during prolonged exercise in the heat. Oral propranolol (160 mg/day), atenolol (100 mg/day) or matching placebo were taken for 6 days each by 11 healthy young adult caucasian males. Subjects participated in 2 h of block-stepping at a work rate of 54 W in an environmental chamber with a temperature of 33.2 +/- 0.3 degree C dry bulb and 31.7 /+- 0.3 degree C wet bulb, 2 h after ingestion of the final dose of each drug. Both active agents produced similar marked (P less than 0.001) increases in subjective perception of effort, the mechanism of which was not immediately evident from changes in serum electrolytes, blood glucose, blood lactate, or ventilatory parameters. Propranolol did, however, cause a greater rise in serum K+ than placebo (P less than 0.02) and atenolol (P = NS) after exercise. Although rectal and mean skin temperatures were insignificantly altered by beta-adrenoceptor blockade, an increased total sweat production was noted with propranolol (P less than 0.01 vs. placebo) and to a lesser degree atenolol (P = NS vs. placebo) therapy. Analysis of the time course of sweat production showed the propranolol-mediated enhancement of sweating to ensue largely during the initial hour of block-stepping and to be transient in nature. The scientific and clinical implications of this observation will be dependent upon the precise underlying mechanism, a factor not identified by the present study.     

Do all human urinary infections with Schistosoma mattheei represent hybridization between S. haematobium and S. mattheei?

Enzyme electrophoresis indicated that all Schistosoma mattheei eggs passed in the urine of humans derive from S. mattheei females in copula with S. haematobium males. It appears that S. mattheei males do not reach sexual maturity in man; however, S. haematobiumxS. mattheei males possibly do.     

ITS2 ribosomal RNA indicates Schistosoma hippopotami is a distinct species

The internal transcribed spacer region of the ribosomal RNA, ITS2, was sequenced from a singlé specimen of S. hippopotami collected from a pulmonary artery of the hippopotamus, Hippopotamus amphibius in South Africa. The nucleotide sequence was aligned with those of S. mansoni, S. rodhaini, S. haematobium, S. intercalatum, S. curassoni. S bovis and S. japonicum. Both maximum parsimony and genetic distance analyses were performed on these data sets. Using S. japonicum as outgroup to the African schistosomes, a single most-parsimonious tree was obtained of length 64 steps with a consistency index of 1. S. hippopotami was the sister-group to the remaining African species. This species has lateral-spined eggs and its basal position in the tree suggests that this condition is primitive and that terminal-spined eggs developed secondarily. Molecular data clearly show that S. hippopotami cannot be considered synonymous with S. mansoni. Assuming the hippopotamus is the normal host of S. hippopotami, phylogenetic analysis is consistent with an ancient association between schistosomes and ungulates.     

A Mads-Box Homologue in Ustilago Maydis Regulates the Expression of Pheromone-Inducible Genes but Is Nonessential

Mating and pathogenic development in the smut fungus Ustilago maydis are controlled by a pheromone/receptor system and two homeodomain proteins, bEp and bWp, which form heterodimers in nonallelic combinations. We describe the isolation of a gene, umc1, encoding a MADS-box protein, which displays significant similarity to the Saccharomyces cerevisiae MCM1 gene. umc1 complemented the viability defect of yeast mcm1 mutants. In U. maydis, umc1 deletion mutants were viable and pathogenic development was unaffected. Nevertheless, the basal expression levels of several pheromone-inducible genes were significantly reduced leading to an attenuated mating reaction. In contrast to S. cerevisiae, where Mcm1p plays a crucial role in the cell-type specific expression of a- and α-specific genes, the U. maydis umc1 gene appears to have only a modulatory effect on the expression of mating type-specific genes.     

Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line.

We demonstrated that a subclone of an Abelson murine leukemia virus-transformed B-lymphoid cell line switched from mu to gamma 2b expression in vitro, by the classical recombination-deletion mechanism. In this line, the expressed VHDJH region and the C gamma 2b constant region gene were juxtaposed by a recombination event which linked the highly repetitive portions of the S mu and S gama 2b regions and resulted in the loss of the C mu gene from the intervening region. An additional recombination event in this subclone involved an internal deletion in the S mu region of the expressed (switched) allele. One end of this deletion occurred very close to the switch recombination point. Despite the recombination-deletion mechanism of switching, the gamma 2b-producing line retained two copies of the C mu gene and two copies of the sequence just 5' to the S gamma 2b recombination point. The possible significance of the retention of these sequences to the mechanism of class switching is discussed.     

Specificity of two isolated wheat carboxypeptidases

The substrate specificity of two purified carboxypeptidases from germinated wheat has been examined. Both enzymes were active on a wide variety of carbobenzoxy substituted peptides but inactive with unsubstituted dipeptides. Neither enzyme was active upon endoprotease or amidase substrates and only low levels of esterase activity were evident. In time course studies, both enzymes gave rapid non-specific sequential release of amino acids, including proline, from the carboxyterminal of proteins and polypeptides of known amino acid sequence.