A. Salvaggio

Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy

Antigen‐ and mitogen‐stimulated cytokine production by peripheral blood mononuclear cells (PBMC) of 50 pregnant women and 31 age‐ and sex‐matched non‐pregnant controls were analysed to determine whether changes in cytokine production occur during normal and pathologic human gestation. The pregnant women, consecutively enrolled during a 3‐month period, were undergoing a normal, non‐pathologic pregnancy at the time of entry into the study, and underwent ultrasound examination to ascertain the exact week of pregnancy and the vitality of the fetus. Forty of the 50 pregnancies (80%) terminated physiologically with the birth of normal babies. Spontaneous abortions were observed in 5/50 (10%) women, and five women gave birth to newborns small for gestational age (SGA). A decrease in the production of IL‐2 and interferon‐gamma (IFN‐γ) accompanied by an increase in production of IL‐4 and IL‐10, was observed in normal pregnancy, with the lowest quantities of IL‐2 and IFN‐γ and the highest quantities of IL‐4 and IL‐10 present in the third trimester of pregnancy. Statistically significant increased production of both IL‐2 and IFN‐γ and reduced production of IL‐10 characterized pathologic pregnancies and distinguished them from normal pregnancies. These preliminary data suggest that a type 2 cytokine profile may be associated with normal human pregnancy, whereas the lack of a dominant type 2 cytokine profile may be indicative of a pathologic pregnancy.

High Sensitivity of Glutamate Uptake to Extracellular Free Arachidonic Acid Levels in Rat Cortical Synaptosomes and Astrocytes

Abstract: By using both synaptosomes and cultured astrocytes from rat cerebral cortex, we have investigated the inhibitory action of arachidonic acid on the high‐affinity glutamate uptake systems, focusing on the possible physiological significance of this mechanism. Application of arachidonic acid (1–100 μM) to either preparation leads to fast (within 30 s) and largely reversible reduction in the uptake rate. When either melittin (0.2–1 mg/ml), a phospholipase A2 activator, or thimerosal (50–200 μM), which inhibits fatty acid reacylation in phospholipids, is applied to astrocytes, both an enhancement in extracellular free arachidonate and a reduction in glutamate uptake are seen. The two effects display similar dose dependency and time course. In particular, 10% uptake inhibition correlates with 30% elevation in free arachidonate. whereas inhibition ≥60% is paralleled by threefold stimulation of arachidonate release. In the presence of albumin (1–10 mg/ml), a free fatty acid‐binding protein, inhibition by either melittin, thimerosal, or arachidonic acid is prevented and an enhancement of glutamate uptake above the control levels is observed. Our data show that neuronal and glial glutamate transport systems are highly sensitive to changes in extracellular free arachidonate levels and suggest that uptake inhibition may be a relevant mechanism in the action of arachidonic acid at glutamatergic synapses.

Thymus volume correlates with the progression of vertical Hiv infection

BACKGROUND The thymus is the organ responsible for the maturation and selection of T lymphocytes and is thus pivotal in allowing the development of a functional immune system. Because in HIV infection cell-mediated immune responses are severely impaired, we studied the role of thymus in the control of the progression of HIV infection to AIDS. METHODS Thymic volume was analysed by magnetic resonance imaging in 31 vertically HIV-infected children. Plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined in the same patients. RESULTS Thymic volume was not correlated with age or nutritional status; thymic volume was nevertheless correlated with CD4 T-lymphocyte counts and with the percentage and absolute number of CD45RA+CD62L+ (naive) T lymphocytes. In addition, the ability of peripheral blood mononuclear cells to proliferate upon tetanus stimulation was directly proportional to thymic volume. Finally, a negative correlation was detected between thymic volume and HIV viral load. CONCLUSION Because low HIV plasma viraemia and preserved immune function are favourable prognostic indices in HIV disease, these data indicate that an immunological, thymic-dependent control of the progression of HIV infection might be possible, at least in vertically transmitted HIV infection.

Increased levels of CD8+ and CD4 + 45RA + lymphocytes in schizophrenic patients

Peripheral blood (PB) lymphocyte subpopulations, IgG, IgM, IgA and IgE serum immunoglobulins and C3 and C4 complement fractions were evaluated in 29 schizophrenic patients, 31 of their relatives and 20 healthy subjects. The patients fulfilled DSM-III criteria for schizophrenia, and were unmedicated for 3 months prior to the PB sample collection. When compared to healthy controls and their own relatives, the schizophrenic patients showed a lower level of CD4+ cells, while the CD4+ 45RA+ (naive) subset was significantly higher. Conversely, the number of CD4+ 45RA- (memory) lymphocytes was significantly lower in schizophrenic patients in comparison to their relatives and controls, while the CD8+ supressor/cytotoxic T-cell percentage was significantly higher. No significant differences were observed for the IgG, IgM, IgA, IgE and C3 and C4 complement fraction levels among the three groups. The present data confirm the presence of immunological abnormalities in schizophrenic patients and suggest a possible role of environmental factors in the triggering of an autoimmune pathogenic mechanism.

Immune responses to antigens of human endogenous retroviruses in patients with acute or stable multiple sclerosis

A possible role for human endogenous retroviruses (HERV) in the pathogenesis of MS was investigated by analyzing HERV peptides-stimulated proliferation and cytokine production in MS patients with acute (AMS) or stable (SMS) disease. HERV peptides specific-proliferation and type 1 cytokine production by peripheral blood mononuclear cells was observed in AMS but not in SMS individuals, in whom a type 2 cytokine profile dominates. HERV peptides-stimulated immune responses were modified by changes in disease expression; mediated by CD4+ T lymphocytes; and not related to HLA class II molecules. These data suggest the possibility of a pathogenic role for HERV and HERV-specific immune responses in MS.

Hypoglycemia-activated K+ channels in hippocampal neurons

Channels linking the electrical and metabolic activities of cells (KATP channels) have been described in various tissues, including some brain areas (hypothalamus, cerebral cortex and substantia nigra). Here we report the existence in hippocampal neurons of K+ permeant channels whose activity is regulated by extracellular glucose. They are open at the cell resting potential and respond to transient hypoglycemia with a reversible increase in activity. The one type so far characterized has a conductance of approximately 100 pS in isotonic K+, is inhibited by the sulphonylurea glibenclamide (1 microM), and is activated by the potassium channel opener lemakalim (0.1-1 microM). These data provide a direct demonstration of the presence, in hippocampal neurons, of glucose-sensitive channels that could belong to the KATP family.

Plasma viremia and virus phenotype are correlates of disease progression in vertically human immunodeficiency virus type 1-infected children

OBJECTIVE To analyze the relationships among HIV-1 plasma viremia, phenotype and CD4 T cell counts in vertically infected children. METHODS Plasma viremia was quantified in 37 vertically infected children at different stages of the disease by a standardized molecular assay. Virus isolation and non-syncytia-inducing or syncytia-inducing (SI) HIV-1 phenotype evaluation were performed in parallel. RESULTS HIV-1 RNA genomes were found to be significantly different in CDC clinical classes N, A, B and C (P = 0.0135) and in immunologic classes 1, 2 and 3 (P = 0.0110). None of the children in Class N or A harbored HIV-1 isolates with SI phenotype, whereas SI primary isolates were detected in 2 of 7 (29%) and 7 of 10 (70%) Class B and C children, respectively. Similarly SI variants were present in only 9 of 13 children in immunologic Class 3 (70%). When stratified according to the increasing severity of virologic status, the children showed a significant difference (P = 0.0458) in viral burden. CONCLUSIONS Clinical symptoms, the most dramatic being reduction in the number of CD4 lymphocytes, and the highest plasma viremia levels were observed in the children in whom fast replicating, highly cytopathic SI variants were isolated. These data extend the virologic characterization of vertically HIV-1 infected children and suggest that both the plasma viremia levels and phenotype of primary isolates are viral correlates of disease progression in vertically infected children.

Prevalence of anti-HCV in subjects of various age groups.

Abstract812 serum samples from 382 males and 430 females from various age groups were examined. All the samples were tested for anti-HCV hepatitis C virus, anti-HBc and HBsAg with an enzymeimmunnassay. The total serum prevalence was 2.9% for anti-HVC, 22.2% for anti-HBc and 4.6% for HBsAg. The seropositivity rates of anti-HCV and anti-HBc tended to increase with age, while for HBsAg a more regular pattern was observed for the different subject groups. The fact that anti-HCV are more frequently found together with HBV markers confirms the existence of similar modes of transmission of the two viruses.

Sexual transmission of hepatitis C virus and HIV-1 infection in female intravenous drug users

We examined the relationship between the presence of antibody to HCV and sexually transmitted diseases in 151 female, intravenous drug users aged 17–43 years. Anti-HCV was present in 49 of 66 HIV-1-negative women (74.2%), and 63 of 85 HIV-1-positive women (74.1%). Anti-HCV seropositivity was significantly related to sexually transmitted infections (Ureaplasma urealyticum infections excluded) in HIV-1-seronegative women, but not in HIV-1-positive women. Also, in HIV-1-negative subjects, Trichomonas vaginalis infections (and infections with M. hominis) were significantly related to anti-HCV seropositivity, and a positive relation between the number of sexual partners and the presence of anti-HCV was demonstrated. In HIV-1-positive subjects a shared use of needles and syringes was more likely, and an increased parenteral exposure to HCV may decrease the relative contribution by sexual transmission. However, in HIV-1-negative subjects, sexual transmission of HCV appears to be both a possible and important means of transmission.

An electrophysiological method to assess the distribution of the sensory propagation velocity of the digital nerve in normal and diabetic subjects

We report a new computer-assisted collision method to evaluate sensory conduction velocity (SCV) distribution in the digital nerve of the middle finger in normal subjects and in insulin-dependent diabetic subjects without any neurological impairment. Distribution curves were monomodally shaped in controls, indicating a greater proportion of fibers with relatively slow conduction velocity and a lesser proportion of fibers with faster velocity. In most diabetic nerves, a monomodal trend of the SCV distribution indicated a definite reduction in high and intermediate SCV. In a small proportion of nerves, the SCV distribution tended to be bimodal, with an absolute maximum corresponding to lower velocities and a relative maximum to intermediate-fast velocities. Slowing of the intermediate velocity, or loss of fibers of intermediate velocity, can be hypothesized to represent the early electrical evidence of a subclinical polyneuropathy in insulin-dependent diabetic subjects.