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Biomedical subjects

M E Rossi

Publications and source records attributed to M E Rossi.

At least 37 records · Page 2Linked to original sources

Hemochrome parameters during the first two years of life in children with perinatal HIV-1 infection.

Monthly hemochrome parameters were obtained during the first 2 years of age in 22 children with perinatal human immunodeficiency virus type-1 (HIV-1) infection and in 58 exposed seroreverted children. Timing and predictive value of hemochrome modifications were investigated. Exclusion criteria were hemoglobinopathies and zidovudine (AZT) treatment in pregnancy. When AZT treatment was undertaken children were eliminated from the study. From the second month of life red blood cell (RBC) counts, hemoglobin (Hb) concentrations, and hematocrit values were significantly lower in infected than in uninfected children. RBC counts progressively diverged in infected and uninfected children, and mean values in the former group never reached 4.10(12)/L. No difference was observed in Hb content ratios and RBC size parameters. At 2 months RBC counts, Hb concentrations, and hematocrit values below reference values were associated with a 15.8 (95% confidence limits [CL]: 5.5-48.8) relative risk of being infected. In infected infants aged 5 months a decrease in these parameters was associated with an 11.2 (95% CL: 1.6-77.8) relative risk of developing eventual severe clinical outcome. Low RBC counts, Hb concentrations, and hematocrit values may be included among predictive criteria in infants of HIV-1 infected mothers.

Anemia↗

Pathogenesis of posttransfusion viral hepatitis in children with beta-thalassemia.

The pathogenesis of posttransfusion hepatitis was determined in 14 children with beta-thalassemia. All had blood samples obtained in 1980 or 1981, were vaccinated against hepatitis B virus in 1983 and had another serum sample collected in 1989. Seven children had detectable antibodies against hepatitis C virus before vaccination, and all were positive in 1989. With specific solid-phase enzyme immunoassays, all children had antibodies against hepatitis B virus, X and polymerase antigens in 1981, and six had one or both antibodies in 1989. Hepatitis B virus infection was confirmed by means of polymerase chain reaction, which demonstrated virus DNA in 13 of the 14 children. The amplification products spanning the X/precore region were smaller than expected, suggesting mutations in this region. Cloning and sequencing of these products revealed deletions spanning part or all of the X gene. The results show that these children were infected with hepatitis B virus even without other markers in serum, that hepatitis B persists years after vaccination and that such infections are associated with the presence of X deletion mutants. Coinfection with hepatitis B and C viruses, the former containing a new class of variants, is common in children with beta-thalassemia.

Adolescent↗

High levels of IgA in HIV-1-perinatally-infected children. Antigen specificity and possible role of increased substance P plasma levels.

The specificity of IgA against food, inhalant, bacterial and fungine antigens as well as for HIV-1 proteins was investigated in 14 HIV-1-infected children (CDC stage P-2) and 15 controls. IgA against food- and inhalant antigens as well as against tetanus toxoid were significantly more often present in the HIV positive children than in controls. No difference between the two groups was present for IgA against Candida albicans. A significant increase of substance P, a strong IgA synthesis inducing neuropeptide, was demonstrated in the plasma of HIV-1 infected children. In conclusion, high levels of IgA seem to reflect a complex immune dysfunction in which many factors are involved. The importance of neuroimmune dysregulation is discussed.

Antibody Specificity↗

Impaired superoxide anion, platelet-activating factor, and leukotriene B4 synthesis by neutrophils in cirrhosis.

BACKGROUND: Several alterations of polymorphonuclear leukocyte (PMN) function were found in alcoholic cirrhotics that may contribute to augmented susceptibility to infections. We evaluated function and synthesis of lipid mediators in PMN obtained from nonalcoholic cirrhotics. METHODS: We evaluated the phagocytic and chemotactic response together with superoxide anion (O2-), leukotriene B4, (LTB4) and platelet-activating factor (PAF) production in response to different stimuli in PMN from nonalcoholic cirrhotics as compared with controls. RESULTS: PMN from cirrhotics showed, after stimulation with opsonized zymosan (STZ) and phorbol-12-myristate-13-acetate, a reduced capacity to produce O2- when compared with controls. [3H]acetate incorporation into PAF was significantly higher in PMN obtained from controls in respect to cirrhotics. Gas chromatography/mass spectrometry analysis confirmed a reduced PAF synthesis by PMN obtained from cirrhotics. LTB4 production from PMN, after stimulation with calcium ionophore (A23187) and STZ, was significantly reduced in cirrhotics. [3H]arachidonic acid release from prelabeled PMN, measured upon stimulation with A23187 and STZ, was higher in controls than in cirrhotics. CONCLUSIONS: An altered synthesis of LTB4 and PAF is associated with an impaired O2- production by PMN in nonalcoholic cirrhosis. Reduced synthesis of lipid mediators may be related to an altered phospholipase A, activity.

Adult↗

Hepatitis C virus antibodies in a long-term follow-up of beta-thalassaemic children with acute and chronic non-A non-B hepatitis.

The presence of antibodies toward hepatitis C virus (HCV) was examined in 78 polytransfused beta-thalassaemic children. The anti-HCV status was correlated with acute and chronic non-A non-B (NANB) hepatitis that developed during a follow up of about 13 years. Anti-HCV was present in 83.3% of children with acute NANB hepatitis and in 82.9% of those with chronic NANB hepatitis. The percentage of chronic evolution was 56.7% for acute anti-HCV positive NANB hepatitis and 50.0% for anti-HCV negative NANB hepatitis. The long-term persistence of anti-HCV antibodies did not correlate with chronic evolution of liver infection in thalassaemic patients. Histological features of chronic hepatitis showed little or no difference between HCV associated or non-associated liver disease. The multifactorial liver injury in beta-thalassaemic children explains the high prevalence of cirrhosis (about 30%) observed in these patients with NANB hepatitis. On the other hand, independent of liver disease, some patients never seroconverted during the follow up in spite of the high number of transfusions suggesting the existence of "non-responders".

Acute Disease↗

VIP restores natural killer cell activity depressed by hepatitis B surface antigen.

Vasoactive intestinal peptide (VIP) has recently been shown to bind to human lymphocytes and modulate immune functions. The ability of VIP in restoring natural killer (NK) cell activity depressed by hepatitis B surface antigen (HBsAg) has been investigated in the present research. Human lymphocytes were incubated with HBsAg and, after washing, a 4-hr cytotoxicity assay was performed. VIP was coincubated with lymphocytes during the preincubation with HBsAg or, alternatively, throughout the cytotoxicity assay. The study revealed that VIP, either preincubated or coincubated in the 4-hr assay, strongly restores NK cell activity depressed by viral antigen. This is noteworthy considering that a number of lymphocyte modulators such as interferons fail in restoring viral-dependent NK cell activity depression. In contrast with previous reports, even when coincubated in the 4-hr assay, VIP is a strong activator of NK cell activity. Further studies will be required to understand which mechanisms are involved in the interrelation between VIP and NK cells during viral infections.

Cytotoxicity, Immunologic↗

Five-year follow-up of vaccination against hepatitis B virus in newborns vaccinated with a reduced number of doses.

The protective efficacy and long-term immunogenicity of a schedule with a reduced number of vaccinations in infants born to mothers positive for hepatitis B surface antigen (HBsAg) has been investigated: 494 infants immunized with a plasma derived hepatitis B vaccine (Hevac B Pasteur) at day 20 after birth and 2 months later were studied. Anti-HBs seroconversion rate was 96% after the second dose, a value similar to that obtained in older children. At 5 years of life anti-HBs at protective levels was still 95.8%. In conclusion, we suggest that this effective and economical reduced vaccination schedule, which before this study was applied to older children, can be used in newborns from HBsAg positive mothers with good protective efficacy shifting the beginning of active immunization from birth to day 20.

Age Factors↗

Permeability characteristics of deoxygenated sickle cells.

This study investigated the effect of acute deoxygenation on membrane permeability characteristics of sickle cells. Measured fluxes of Na+ and K+ in ouabain-inhibited cells, of chloride and sulfate exchange in 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS)-inhibited and untreated cells, and of erythritol, mannitol, and arabinose in cytochalasin B-inhibited cells indicated that a deoxygenation-induced permeability change occurred in sickle cells only for cations and chloride. Monovalent cation permeabilities increased five-fold, and chloride influx into DIDS treated cells was enhanced nearly threefold on sickle cell deoxygenation. In contrast, no detectable increase in permeability to the other solutes was found. To gain perspective on these findings, similar measurements were performed in normal cells treated with diamide, an agent shown by others to induce a coupled increase in membrane permeability and phospholipid translocation, reminiscent of deoxygenation-induced changes in sickle cells. Although the increase in cation permeability was no greater than that in sickled cells, treatment with 2 mmol/L diamide also produced a twofold increase in the first order rate constants for sulfate exchange and mannitol efflux, indicating a relatively nonselective permeability increase that permitted flux of larger solutes than in the case of deoxygenated sickle cells. These results suggest that the deoxygenation of sickle cells induces a permeability increase that is relatively insensitive to charge, but is restrictive with respect to solute size.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

False diagnosis of non-A/non-B hepatitis hiding two cases of cystic fibrosis.

We report two cases of children followed for many years with an original diagnosis of non-A/non-B hepatitis. One child developed serious cirrhosis with portal hypertension. Long-term observation of the course of their hepatic disease provided the diagnosis of cystic fibrosis. These cases demonstrate that cystic fibrosis though rarely presenting with initial hepatic signs, can manifest itself with only long-term hepatic symptoms. We therefore strongly recommend analysis of sweat chloride concentration in cases of hepatic disease of unknown origin.

Adolescent↗

Modulation by human milk of IgG subclass response to hepatitis B vaccine in infants.

The influence of breast and formula feeding on specific anti-hepatitis B surface antigen (HBsAg) IgG subclass production and distribution has been investigated in 40 healthy infants, born to HBsAg-positive mothers and vaccinated against hepatitis B virus (HBV). Twenty children were bottle fed and 20 were breast fed. Specific subclasses were detected at the 4th and 12th months using an enzyme-linked immunosorbent assay with monoclonal antibodies. A defect in total IgG and IgG subclasses was previously excluded. Significant differences were observed both at the 4th and 12th months for IgG1 and IgG2. Breast-fed infants had significantly higher levels of specific IgG2 (about three times higher), while IgG1 levels were significantly higher in formula-fed infants. Anti-HBsAg IgG4 levels were always higher in bottle-fed infants, but a statistical significance was never present. No difference was found in specific IgG3 levels. This study reports the evidence that breast feeding influences specific IgG subclass synthesis against a viral antigen and suggests an immunologic modulation of the response to vaccines dependent not only on age but also on factors present in human milk.

Adult↗

Defective in vitro production of gamma-interferon and tumor necrosis factor-alpha by circulating T cells from patients with the hyper-immunoglobulin E syndrome.

Circulating T cells from four patients with the hyper-IgE syndrome were found to produce significantly lower concentrations of interferon-gamma (IFN-gamma) in response to stimulation with phytohemagglutinin (PHA) than did T cells from eight age-matched healthy controls, three patients with atopic dermatitis and one patient with chronic granulomatous disease. A clonal analysis revealed that patients with hyper-IgE syndrome had markedly lower proportions of circulating T cells able to produce IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in comparison with controls. In contrast, the proportions of peripheral blood T cells able to produce IL-4 or IL-2 were not significantly different in patients and controls. All the four patients with hyper-IgE syndrome showed high proportions of circulating CD4+ helper T cells able to induce IgE synthesis in allogeneic B cells, as well. Such an activity for IgE synthesis appeared to be positively correlated with IL-4 production by T cells and inversely related to the ability of the same T cells to produce IFN-gamma. Since IFN-gamma exerts an inhibitory effect on the synthesis of IgE and both IFN-gamma and TNF-alpha play an important role in inflammatory reactions, we suggest that the defective production of IFN-gamma may be responsible for hyperproduction of IgE and the combined defect of IFN-gamma and TNF-alpha may contribute to the undue susceptibility to infections seen in patients with hyper-IgE syndrome.

Adolescent↗

Fatty acid chain-shortening activity in the pulmonary type II cell.

Type II cells obtained from fetal rabbit lung tissue in culture were incubated with [14C]palmitic and [14C]stearic acids labeled at either the carboxyl or the terminal methyl groups. Significant chain shortening of [18-14C]stearic acid to radiolabeled palmitic acid was observed, with little chain shortening of palmitic acid to myristic acid. Incorporation of 14C into palmitic acid by beta-oxidation followed by de novo fatty acid biosynthesis was not detectable under the same experimental conditions. The palmitic acid supplied by chain shortening was preferentially incorporated into phosphatidylcholine instead of other lipids. Fatty acid chain-shortening activity in the type II cell appears to be capable of increasing the amount and relative proportion of palmitic acid available for phosphatidylcholine biosynthesis.

Animals↗

Occurrence and subclass distribution of IgG antibodies to dietary antigens in children with atopic dermatitis and in their mothers.

Occurrence and subclass distribution of IgG to alpha-lactalbumin (ALA), beta-lactoglobulin (BLG), and ovalbumin (OA) have been determined in 30 children with atopic dermatitis (AD) and in their mothers. Thirty nonatopic (NA) children and their mothers were studied as controls. Total IgE and IgE to ALA, BLG, OA, Dermatophagoides pteronyssinus, and Lolium perenne were also investigated. The main purpose of this study was to determine whether in humans, as observed in animals, maternal allergen-specific IgG influences allergen-specific IgE synthesis in children. IgG1, IgG2, IgG3, and IgG4 to ALA, and IgG1 and IgG2 to OA were more frequent in AD children than in NA children. As compared with mothers of NA children, mothers of AD children had similar frequency and levels of IgG subclasses to BLG and to OA, but a higher frequency of IgG1, IgG2, and IgG3 to ALA. In no case did total or allergen-specific IgE levels correlate with any subclass of allergen-specific IgG, which in turn influenced neither total IgE levels nor allergen-specific IgE distribution. The presence of allergen-specific IgG of any subclass in mothers was not associated with modifications in total IgE levels nor in allergen-specific IgG subclass distribution in AD children. But occurrence of IgE to OA was higher in AD children whose mothers had IgG4 to OA. This finding may be a model of interference in specific IgE response in the child caused by isotype response in the mother.

Adult↗

Fatty acids of pulmonary surfactant phosphatidylcholine from fetal rabbit lung tissue in culture. Biosynthesis of n-10 monoenoic fatty acids.

We have previously reported that fetal rabbit lung tissue in organ culture produces a lamellar body material (pulmonary surfactant) with a lower percentage of disaturated phosphatidylcholine than is typically found in rabbit lung in vivo (Longmuir, K.J., C. Resele-Tiden, and L. Sykes. 1985. Biochim. Biophys. Acta. 833: 135-143). This investigation was conducted to identify all fatty acids present in the lamellar body phosphatidylcholine, and to determine whether the low level of disaturated phosphatidylcholine is due to excessive unsaturated fatty acid at position sn-1, sn-2, or both. Fetal rabbit lung tissue, 23 days gestation, was maintained in culture for 7 days in defined (serum-free) medium. Phospholipids were labeled in culture with [1-14C]acetate or [U-14C]glycerol (to follow de novo fatty acid biosynthesis), or with [1-14C]palmitic acid (to follow incorporation of exogenously supplied fatty acid). Radiolabeled fatty acid methyl esters obtained from lamellar body phosphatidylcholine were first separated by reverse-phase thin-layer chromatography (TLC) into two fractions of 1) 14:0 + 16:1 and 2) 16:0 + 18:1. Complete separation of the individual saturated and monoenoic fatty acids was achieved by silver nitrate TLC of the two fractions. Monoenoic fatty acid double bond position was determined by permanganate-periodate oxidation followed by HPLC of the carboxylic acid phenacyl esters. Lamellar body phosphatidylcholine contained four monoenoic fatty acids: 1) palmitoleic acid, 16:1 cis-9; 2) oleic acid, 18:1 cis-9; 3) cis-vaccenic acid, 18:1 cis-11; and 4) 6-hexadecenoic acid, 16:1 cis-6. In addition, 8-octadecenoic acid, 18:1 cis-8, was found in the fatty acids of the tissue homogenate. The abnormally low disaturated phosphatidylcholine content in lamellar body material was the result of abnormally high levels of monoenoic fatty acid (principally 16:1 cis-9) found at position sn-2. Position sn-1 contained normal levels of saturated fatty acid. The biosynthesis of the unusual n-10 fatty acids was observed from the start of culture throughout the entire 7-day culture period, and was observed in incubations of tissue slices of day 23 fetal rabbit lung. This is the first report of the biosynthesis of n-10 fatty acids (16:1 cis-6 and 18:1 cis-8) in a mammalian tissue other than skin, where these fatty acids are found in the secretory product (sebum) of sebaceous glands.

Animals↗

Selectivity in IgG subclass response to hepatitis B vaccine in infants born to HBsAg-positive mothers.

IgG subclasses of antibodies to the hepatitis B surface antigen (HBsAg) in sera from 40 healthy infants immunized with the vaccine against hepatitis B virus (HBV) were detected using an enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies. The infants were born to asymptomatic HBsAg-positive mothers. Total serum IgG subclasses were also tested to exclude a deficiency of certain subclasses in these infants but their distribution was the one expected according to age. In contrast, IgG subclass antibodies to HBsAg were predominantly IgG1 and IgG4. The collected data indicate that infants produce significantly higher levels of IgG1 and IgG4 than IgG2 and IgG3 in response to the vaccine for HBV. The IgG4 response to anti-viral vaccinations is uncommon. The role of that IgG4 subclass is not yet clear: even if an anaphylactic role was suggested, no adverse reactions were observed in vaccinated children.

Adult↗