Prognostic value of adenosine deaminase compared to other markers for progression to acquired immunodeficiency syndrome among intravenous drug users.

This study was designed to determine the prognostic value of erythrocyte adenosine deaminase (ADA) as a possible indicator of progression to AIDS, and compare this with other known cellular and serological markers. At the end of a 3-year study, a cohort of 114 human immunodeficiency virus-1 (HIV-1) seropositive intravenous drug users (IVDUs) from the five different Center for Disease Control (CDC) groups was examined in order to estimate the prognostic relevance with respect to the progression to acquired immunodeficiency syndrome (AIDS) of each of the following markers at baseline value: number and percentage of CD4+ T cells, number of CD8+ T cells, CD4+/CD8+ ratio, IgA and beta 2 microglobulin and ADA levels, and the presence of HIV antigens. Moreover, 57 IVDUs belonging to II and III CDC groups were analyzed in a follow-up study at 6-month intervals, in order to evaluate and compare the behavior of each marker over time. The prognostic significance of each marker was assessed by computing the survival distribution and the Cox analysis in a multivariate model providing the set of markers with greatest predictive value. The levels of ADA and the CD4+/CD8+ ratio showed a linear association with disease staging, whereas beta 2 microglobulin and CD4+/CD8+ ratio were the best predictors for AIDS progression. A highly significant increase in ADA and beta 2 microglobulin was observed during follow-up. The results obtained among HIV-positive IVDUs clearly indicate that the erythrocyte ADA may be considered a reliable marker of the development of HIV infection from the intermediate stages of the disease onwards.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis, spectroscopic and structural characterization, and biological activity of aquachloro (pyridoxal thiosemicarbazone) copper(II) chloride.

The synthesis, spectroscopic studies, x-ray crystal structure, and biological properties of the complex [Cu(H2L)(OH2)Cl]Cl (1) (H2L = pyridoxal thiosemicarbazone) are reported. The compound crystallizes in space group P2(1)/n, a = 12.128(2), b = 9.096(2), c = 13.592(2) A, beta = 108.65(2) degrees, U = 1420.7 A3, and Z = 4. The molecular structure consists of discrete cations [Cu(H2L)(OH2)Cl]+ and Cl- anions. Each copper atom is in an approximately square pyramidal environment involving the phenolic oxygen, the imine nitrogen, the sulphur, and a water oxygen in the equatorial positions, while a chlorine atom occupies the axial position. The structure of this complex is compared to that of the dimeric [(Cu(HL)(OH2))2]Cl2.2H2O (2) obtained under different experimental conditions, to that of a Co(III) complex with the same ligand [Co(HL)L].4.5H2O (3) and to that of the free ligand H2L, especially in relation to its biological activity. Compounds 1 and 2 have not antiviral action in vitro with respect to RNA viruses, show an inductive effect on Friend erythroleukemia cells (FLC), erythroid differentiation and a suppressive effect regarding FLC proliferation. Complex 3 and the free ligand do not have biological activity.

Contractile effect of endothelin-2 on the isolated human saphenous vein.

The contractile effect of endothelin-2 was investigated in isolated human saphenous vein preparations. Spare segments taken from revascularized patients were set up in isolated organ chambers and mechanical activity was recorded under isometric conditions. Endothelin-2 (10(-11)-10(-7) M) evoked a dose-dependent contractile response, having the same efficacy as noradrenaline and 100 times its potency. Conversely, the "selective" ETB agonist, C-terminal hexapeptide endothelin (16-21), was completely ineffective. The activity of endothelin-2 was not modified by phentolamine, saralasin and indomethacin, thus excluding a direct or indirect activation of alpha-adrenoceptors and angiotensin receptors as well as the synthesis of cyclooxygenase products. Calcium removal from nutrient fluid depressed, but not fully abolished, the contractile effect of endothelin-2; furthermore, calcium channel blockers, verapamil and nifedipine, produced only a partial inhibition of the endothelin-2-induced contractions. These observations suggest that endothelin-2 induces a direct activation of specific receptors in the saphenous vein muscle and that both intracellular and extracellular calcium pools may be involved in the contractile effect of the peptide.

Positive inotropic effect of endothelin-2 on human atrium preparations in vitro.

The inotropic effect of endothelin-2 was investigated on isolated preparations of human atrium taken from patients undergoing cardiac surgery. Pectinate muscle fragments were set up in isolated organ chambers under isometric conditions and electrically stimulated through two ring platinum electrodes. Endothelin-2 (10(-11)-10(-8) M) increased both the force and velocity of contraction in a concentration-dependent manner, giving a maximum response of about 70% of that attainable with histamine or epinephrine. The putative endothelin B receptor agonist, the C-terminal hexapeptide endothelin-(16-21), did not affect inotropic activity. The action of endothelin-2 was not modified by indomethacin and propranolol, thus excluding an involvement of endogenous prostaglandins or catecholamines. The adenylate-cyclase activator, forskolin, and the calcium agonist, Bay K 8644, at concentrations able to enhance the inotropic effect induced by histamine and epinephrine, did not modify the action of endothelin-2. The data show that endothelin-2 has a strong positive inotropic effect on the isolated human myocardium. The effect seems to be independent of the sympathetic system and is unlikely to involve slow channel conductance or cyclic AMP. The lack of activity of endothelin fragment suggests that an endothelin receptor subtype, similar to that found in rat aorta, is present on human atrium.

Discordant expression of terminal transferase and T cell receptor beta chain in fetal and pediatric thymocytes.

Human thymuses at different ages of development were analyzed for TdT+/beta F1+ double-stained cells. beta F1 is a mAb which recognizes a "hidden" framework determinant on the beta chain of the T cell receptor (TCR). We have found that TCR beta chains appear early during thymic ontogenesis and are detectable by 15 weeks of gestation in cells that are TdT-. Paradoxically, the immature CD2- large thymic blasts in late fetal development and in infants are TdT+ but beta chain negative. These data are compatible with the notion that TdT acts as somatic mutagen on TCR beta genes starting only after 20 weeks of gestation. The beta chain proteins which appear early during thymic ontogenesis might reflect expression of incompletely rearranged (DJ), unrearranged, or fully rearranged TCR beta genes in an early wave of thymocyte clonal (beta) diversification, that is, in contrast to later development, independent of TdT.

Prognostic significance of adenosine deaminase determinations in subjects with the lymphoadenopathy syndrome.

The association between human immunodeficiency virus type I (HIV-I) infection and high levels of erythrocyte adenosine deaminase (ADA) has been suggested by Cowan et al [1986]. We have analyzed the specific activities of the same enzyme during different stages of acquired immunodeficiency syndrome (AIDS), including asymptomatic subjects at high risk and patients with lymphoadenopathy syndrome (LAS), AIDS-related complex (ARC), full-blown AIDS, and AIDS encephalopathy (AIDS enc). The ADA activities were significantly higher (P less than .05) in asymptomatic HIV-I serum-positive individuals (13.1 U +/- 1.1) and in different groups of patients (LAS = 23.6 U +/- 10.2; ARC = 23.7 +/- 4.1) than those found in controls (9.5 U +/- 1.8) and in HIV-I serum-negative subjects (10.4 +/- 1.5). In patients with AIDS the mean ADA activity was of 32.3 U +/- 7.1, whereas in two cases with AIDS enc it was of 10 U. A tendency to increase in median ADA values with the progression of the disease was observed. In LAS patients the ADA values presented two distinct subsets falling below and above the cut-off line of 15 U/10(9) erythrocytes, respectively. A specific correlation to drug addition and its duration was observed: LAS subjects who discontinued drug abuse (median addiction time: 3 years) presented ADA values (median = 13 U) that are lower than for addicts (median = 27.2 U; median addiction time = 7 years) and are close to those observed for asymptomatic HIV-I serum-positive group. Evidence was also obtained for a progressive increase of ADA values of LAS patients with disappearance of the product of gag gene. These results suggest that LAS subjects with elevated ADA activities present a longer history of HIV-I infection and a higher probability of developing AIDS.

Different distribution of DNA polymerases alpha and beta in bone marrow and peripheral blood from human leukemia.

An activity gel method was used to analyze the catalytic polypeptides of polymerases alpha and beta in human acute myeloblastic and lymphoblastic leukemia. A 175 kDa alpha-polymerase was found in 85% of bone marrow and in 57% of peripheral blood samples. At variance, a 40 kDa beta-polymerase was found in 94% of peripheral blood and only in 12% of bone marrow samples. No difference in the pattern of polymerase expression was found according to the type of leukemia and the disease status. The role of these enzymes in leukemia and their implications in drug sensitivity are discussed.

Progression of a myelodysplastic syndrome to pre-B acute lymphoblastic leukaemia with unusual phenotype.

This study shows the progression of a myelodysplastic syndrome (MDS) to pre-B acute lymphoblastic leukaemia (ALL) with an unusual phenotype. On diagnosis of leukaemia bone-marrow mononuclear cells were labelled with murine monoclonal antibodies HLA-DR, VIL-A1 (CALLA), 3813, VIM-D5 and with a rabbit antiserum to TdT using a double colour indirect immunofluorescence technique. In addition simultaneous detection of cytoplasmic mu chains (Cy mu) and of TdT was carried out and a direct immunofluorescence analysis for surface membrane immunoglobulins (SmIg) was performed. Two main populations were present: the major one being HLA-DR+, Cy mu+, VIM-D5+, TdT-, CALLA-, SmIg-; the minor one HLA-DR+, Cy mu+, VIM-D5-, TdT+, CALLA-, SmIg-. The progression of our case to acute leukaemia with a population of leukaemic cells each of which demonstrated features of lymphoid and myeloid cells suggests that MDS would originate at the pluripotential stem cell level.

Terminal deoxynucleotidyl transferase in human fetal tissues.

The authors have investigated terminal deoxynucleotidil transferase (TdT) activity in the spleen, liver and thymus of a human foetus of 23 weeks. TdT significant levels have been found and two different molecular forms were defined in each tissue.

Effect of acute and chronic cimetidine administration on glucose tolerance and insulin secretion in man.

The effect of acute and chronic cimetidine administration on glucose tolerance and insulin secretion was studied in healthy male volunteers. Cimetidine was administered intravenously (4 mg X kg-1 followed by 0.7 mg X kg-1 X h-1) in acute studies and by oral route (1 g/die for 4 weeks) in long-term studies. Oral (100 g) or intravenous (0.5 g X kg-1) glucose was used as a stimulus for insulin secretion in both studies. Neither acute nor chronic cimetidine administration modified insulin secretion and glucose tolerance. These data are consistent with the idea that H2-receptors are not involved in the insulinogenic effect of glucose.