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Biomedical subjects

I Quinti

Publications and source records attributed to I Quinti.

At least 19 recordsLinked to original sources
PubMed2001

T-Cell immune activation in children with vertically transmitted hepatitis C virus infection.

Little is known concerning the clinical features, the histological outcome, and the effects on the maturation of immune system of children with vertically-transmitted hepatitis C virus (HCV) infection. Specifically, no data are available on the peripheral distribution of T-cell subsets. The frequency of naive and memory cells, activated T cells, and cytokine-producing T cells was analyzed in nine HCV-infected children born to HCV-positive mothers. In HCV-infected children, the distribution of naive and memory cells was not significantly altered in the CD4 subset whereas within the CD8 subset, an increase of memory and a decrease of naive cells was observed. The frequency of HLA-DR-positive and Fas-positive T cells was increased in HCV-infected children in both CD4 and CD8 subsets. The distribution of Fas-expressing T cells was directly related to that of HLA-DR cells and inversely related to the frequency of naive T cells. In regard with cytokine production we found increased levels of both CD4 and CD8 interferon-gamma (IFN-gamma)-producing cells whereas no difference in the percentage of interleukin-2 (IL-2)-producing T cells was observed. No meaningful correlation was observed between individual T cell subsets and ALT levels or HCV viral load. In conclusion, our results indicate an increased T-cell activation and a shift to a T(H)1 pattern of cytokine production in children with vertically transmitted HCV infection. The cause of this kind of immune response could reside in the persistent antigenic stimulation by chronic HCV infection.

Adolescent↗
PubMed1997

Mutation pattern in the Bruton's tyrosine kinase gene in 26 unrelated patients with X-linked agammaglobulinemia.

Mutation pattern was characterized in the Bruton's tyrosine kinase gene (BTK) in 26 patients with X-linked agammaglobulinemia, the first described immunoglobulin deficiency, and was related to BTK expression. A total of 24 different mutations were identified. Most BTK mutations were found to result in premature termination of the translation product. Mutations were detected in most BTK exons with a predominance of frameshift and nonsense mutations in the 5' end of the gene and missense mutations in its 3' part, corresponding to the catalytic domain of the enzyme. Nonsense and frameshift mutations were associated with diminished levels of BTK mRNA expression, except for a frameshift mutation in exon 17 and two nonsense mutations in exon 2, indicating that these cases are not confined to penultimate exons. One amino acid substitution (R28H) was found in the pleckstrin homology domain's residue, which is mutated in mice bearing the X-linked immunodeficiency phenotype; another substitution (R307G) was identified in the src homology domain 2. All remaining amino acid substitutions were found in the catalytic domain of Btk.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1997

Possible participation of polymorphonuclear cells stimulated by microbial immunomodulators in the dysregulated cytokine patterns of AIDS patients.

Macrophages and polymorphonuclear cells (PMN) play a major role as cells primarily responsive to microbial biological response modifiers (BRM). Although much attention has been given to macrophages, PMN have been relatively underinvestigated. We have recently studied the responses of PMN from HIV- and HIV+ subjects after stimulation with a powerful immunomodulatory fraction from the cell wall of Candida albicans (MP-F2) and compared this to bacterial lipopolysaccharide (LPS). Both cytokine patterns and PMN anticandidal activity were investigated. MP-F2, like LPS, was an active inducer of interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-1 beta production by PMN and monocytes from all subjects. IL-12 was also produced by MP-F2-stimulated PMN in the presence of interferon-gamma (IFN-gamma). PMN from HIV+ subjects showed increased in vitro expression of TNF-alpha and IL-6 genes as determined by semiquantitative reverse transcriptase-polymerase chain reaction. In all subjects, cytokine gene expression was strongly stimulated by MP-F2 or LPS and inhibited by IL-10. Production of IL-6 and TNF-alpha protein (measured by ELISA) was higher in PMN from HIV+ subjects in at least one of the conditions tested (unstimulated or stimulated by LPS or MP-F2). However, the amount of the C-X-C chemokine IL-8 was equal in PMN from HIV- and HIV+ subjects. PMN from HIV+ subjects were at least as active in inhibiting candide growth as PMN from HIV- controls. In both groups PMN were equally stimulated by MP-F2 and LPS. Only in severely neutropenic subjects was there some reduction in the anticandidal activity but not in cytokine responses. When appropriately stimulated by microbial BRM, PMN are active producers of pro-inflammatory and immunomodulatory cytokines. This production is not only totally preserved in HIV+ subjects but may be higher than in PMN from HIV- subjects and may be coupled with an efficient anticandida activity. We suggest that during common bacterial or fungal infections PMN may contribute to the dysregulated production of inflammatory cytokines in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1997

HCV infection in Egyptian patients with acute hepatitis.

The diagnostics of community-acquired acute HCV hepatitis in an endemic area was studied in 110 Egyptian patients with acute jaundice. In the first week of the jaundiced period 30 of 110 patients (27.3%) had anti-HCV antibodies. The majority already showed high levels of anti-HCV IgG (25/30), associated with anti-HCV IgM in nine of them. Five patients showed only an HCV IgM reactivity. Seven had also anti-HEV and/or anti-HBV: their jaundice could then be related to an acute infection caused by those viruses. All patients were infected with genotype 4a, in three associated with the 3a. During the follow-up five patients seroconverted for IgG, while their anti-HCV IgM did not show a uniform pattern of reactivity. Patients with positive serology suspected of an acute HCV infection were older than the patients with other acute hepatitis and showed a lower peak of ALT level. Seroconversion during acute hepatitis strongly indicated HCV as the etiologic agent. However, the detection of anti-HCV IgG antibodies in the jaundiced period showed that the majority of patients had already seroconverted to anti-HCV antibodies; in most of them it is possible to hypothesize a reactivation of a chronic HCV infection.

Acute Disease↗
PubMed1997

Responsiveness of human polymorphonuclear cells (PMNL) to stimulation by a mannoprotein fraction (MP-F2) of Candida albicans; enhanced production of IL-6 and tumour necrosis factor-alpha (TNF-alpha) by MP-F2-stimulated PMNL from HIV-infected subjects.

IL-1beta, IL-6, IL-8 and TNF-alpha production by PMNL from 21 HIV-infected (HIV+), including 11 full-blown AIDS, and 20 HIV-uninfected (HIV-) subjects (matched for age and sex to HIV+ ones) was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and ELISA. PMNL from both categories of subjects were strongly stimulated in their actual cytokine production by a mannoprotein fraction (MP-F2) of Candida albicans, as well as by the bacterial lipopolysaccharide (LPS). These stimulatory effects were apparently due to increased cytokine gene expression and were substantially reversed by the physiological inhibitor IL-10. However, PMNL from HIV+ subjects showed increased IL-6 and TNF-alpha gene expression and produced more IL-6 and TNF-alpha than PMNL from HIV- controls, under similar stimulation conditions. This difference could not be attributed to a given stage of HIV infection, any associated medication, or to a generalized increase of gene expression, as quantitatively similar beta-actin and IL-1beta transcripts were detected. Moreover, no significant difference in IL-8 production by the PMNL from HIV+ and HIV- subjects was observed. Our studies suggest that PMNL from HIV+ subjects might add to other cellular sources of IL-6 and TNF-alpha (e.g. monocytes-macrophages) in contributing to the cytokine-dysregulated pattern typical of the HIV+ patient.

Adult↗
PubMed1997

IL-10 production and CD40L expression in patients with common variable immunodeficiency.

The authors studied CD40 ligant (CD40L) expression and interleukin-10 (IL-10) production in 16 patients with common variable immunodeficiency (CVI). Mean CD40L expression, determined by using cytofluorimetry, and measured as the mean fluorescence intensity following stimulation of peripheral blood mononuclear cells (PBMC) with phorbol myristate acetate (PMA) and calcium ionophore in 12 patients, was comparable to that of controls. However, three CVI patients showed fluorescence intensity in stimulated cells below 2 standard deviations of normal donors' mean and two other patients had only a slight increase of stimulated versus unstimulated cells (< 10 channels). IL-10 production after stimulation of PBMC with both anti-CD3 or anti-CD3 plus PMA gave similar results in CVI patients and normal controls. In vitro stimulation of PBMC with anti-CD40 and various combinations of cytokines (IL-2, IL-4 and IL-10) induced IgG production above 100 ng/ml in one CVI patient out of 13 tested. The data suggest that alterations of IL-10 production are unlikely to play a major role in the pathogenesis of impaired IgG production in most CVI patients. CD40L appears to be normally expressed in two thirds of CVI patients, but it may be functionally defective.

Adolescent↗
PubMed1997

Proliferative responses to PHA, anti-CD3 and antigens in patients with lymphoproliferative disease of granular lymphocytes. Mannoproteins of Candida albicans induce proliferation and cytotoxicity.

In this paper we investigated the lymphoproliferative and cytotoxic responses of peripheral blood mononuclear cells (PBMC) of patients affected with lymphoproliferative disease of granular lymphocytes of T cell origin to mitogens and antigens. Most patients with lymphoproliferative disease of granular lymphocytes (LDGL) showed a severely impaired PBMC proliferative capacity in response to phytohemagglutinin, anti-CD3 and tetanus toxoid, an impairment that, in the case of anti-CD3 response, appears to be related to a defect of phosphorylation in response to triggering. In contrast, at least 50% of the patients had normal proliferation in response to a mannoprotein fraction purified from Candida albicans. These data suggest that some CD3+ GL from LDGL patients, that usually respond poorly to proliferative stimuli in vitro, can be triggered to perform these functions by candidal antigens.

Adult↗
PubMed1997

Iron overload in patients with chronic viral hepatitis: how common is it?

OBJECTIVES: To establish the prevalence of increased hepatic iron content in patients with hepatitis C virus-related chronic hepatitis and to assess the accuracy of serum iron and ferritin in detecting tissue iron overload. METHODS: Serum iron, serum ferritin, and hepatic iron content were determined in 81 consecutive patients undergoing liver biopsy for chronic ALT elevation and hepatitis C virus infection. Moreover, in a subgroup of 28 patients, outcome of a 6-month course of interferon (IFN) treatment (6 million U of recombinant IFN, three times weekly) was determined after a mean follow-up of 24 +/- 6 months and the outcome was compared with the pretreatment values of hepatic iron content. RESULTS: Elevated serum iron or ferritin levels were detected in approximately 40% of patients, but elevated hepatic iron content was observed in only eight patients (10%). One of these patients had a hepatic iron index > 1.9, indicating hemochromatosis. Liver iron content and serum iron levels were not correlated. No differences in hepatic iron content were observed among patients with a sustained response to IFN (seven patients), short-term responders (seven patients), or nonresponders (14 patients). CONCLUSIONS: Ten percent of patients with chronic hepatitis C have elevated hepatic iron content. These patients cannot be identified using serum markers of iron status. The relationship between liver iron and response to IFN treatment requires further prospective investigations.

Adult↗
PubMed1996

HCV infection in a patient with hyper IgM syndrome.

The association between an acquired form of hyper-IgM syndrome and a chronic hepatitis C virus (HCV) infection in a 71-year-old female patient is described. Both diseases were diagnosed at the age of 58 years. She was started on intramuscular and then intravenous immunoglobulin replacement therapy. HCV RNA was detected in 1992. The patient remained in well-balanced clinical condition until 1994, when total and specific anti-HCV IgM levels increased and the patient developed an IgM kappa monoclonal gammopathy. Adherent cells and B cells were HCV RNA positive, while T cells were HCV RNA negative. Anti-IgM reactivity was specifically directed to the core antigen of the HCV. The patient we describe showed a picture of a late-onset form of hypogammaglobulinemia with a progressive increase in IgM antibodies, possibly due to the concomitant HCV infection. It is possible that the immunodeficiency might also result from the HCV infection, with formation of specific antibodies belonging to the IgM class, and that the worsening of the clinical condition may be directly related to the persistent viral infection.

Aged↗
PubMed1996

Hepatitis C virus infection in Italian patients with hypogammaglobulinemia.

We investigated the presence of hepatitis C virus (HCV) infection in 58 patients with humoral immunodeficiencies. Forty-three of these patients had common variable immunodeficiency (CVI), 2 had sporadic hyperimmunoglobulin M (HIM) syndrome, 2 had immunoglobulin G subclass deficiency, 4 had ataxia-telangiectasia (AT), and 7 had X-linked agammaglobulinemia (XLA). Patients with late-onset hypogammaglobulinemia (those with CVI, HIM, or immunoglobulin G subclass deficiency) had a 38.2% prevalence of HCV infection. In patients with XLA or AT, HCV infection was not detectable. Most of the HCV-infected patients had persistent viremia, with histologic findings of chronic hepatitis. Although patients positive for HCV ribonucleic acid (RNA) had received several lots of immunoglobulin, we were unable to detect any correlation between the time that alanine aminotransferase levels increased and the time that intravenous immunoglobulin therapy was given, except in one patient with CVI. Moreover, we found no differences in the number of blood transfusions, surgical procedures, or administrations of intravenous or intramuscular immunoglobulin between HCV RNA-positive and HCV RNA-negative groups. We concluded that: (1) the incidence of HCV infection in patients with hypogammaglobulinemia is much higher than that reported in the Italian general population; (2) although patients with hypogammaglobulinemia have persistent viremia, they do not show an aggressive course of HCV disease, nor does hepatocarcinoma develop; and (3) intravenous immunoglobulins are only one of several possible causes of HCV transmission in patients with humoral immunodeficiencies.

Adult↗
PubMed1996

Elevated aspartic proteinase secretion and experimental pathogenicity of Candida albicans isolates from oral cavities of subjects infected with human immunodeficiency virus.

Isolates of Candida albicans from the oral cavities of subjects at different stages of human immunodeficiency virus (HIV) infection or uninfected controls were examined for (i) production of aspartic proteinase(s), a putative virulence-associated factor(s); (ii) the presence in the fungal genome of two major genes (SAP1 and SAP2) of the aspartic proteinase family; and (iii) experimental pathogenicity in a murine model of systemic infection. It was found that the fungal isolates from symptomatic patients secreted, on average, up to eightfold more proteinase than the isolates from uninfected or HIV-infected but asymptomatic subjects. This differential property was stably expressed by the strains even after years of maintenance in stock cultures. Moreover, representative high-proteinase isolates were significantly more pathogenic for mice than low-proteinase isolates of C. albicans. The characters high proteinase and increased virulence were not associated with a single molecular type or category identifiable through DNA fingerprinting or pulsed-field electrophoretic karyotype, and both SAP1 and SAP2 genes were present in both categories of isolates, on the same respective chromosomes. In conclusion, our data suggest that during HIV infection more-virulent strains or biotypes of C. albicans which are identifiable by direct analysis of virulence determinants are selected. It also appears that the biotype switch to increased aspartic proteinase and virulence properties occurs before the HIV-infected subject enters the symptomatic stage and overt AIDS.

Animals↗
PubMed1995

Apoptosis-related mortality in vitro of mononuclear cells from patients with HIV infection correlates with disease severity and progression.

Peripheral blood mononuclear cells (PBMC) from 103 HIV-infected patients were tested for their mortality rate (MR) when incubated in vitro for 3 days in a culture medium. MR was related to apoptosis as shown by DNA analysis and morphological evaluation of ethidium bromide-stained PBMC by flow cytometry. MR was significantly higher in patients in CDC stage IV as compared to patients in stage II or III (p = 0.017). MR was also higher in patients with low CD4 cells/mm3 (p = 0.014 for patients with < 400 cells; p = 0.001 for patients with < 200 CD4 cells/mm3) and with low percentage of CD4 cells (p = 0.001 for patients with < 10% of CD4 cells). A significant negative correlation was observed between MR and both absolute numbers or percentages of CD4 cells (p < 0.001). The addition of interleukin-2 (IL-2) and fibro-blast-conditioned medium (FCM) to the cultures significantly reduced MR. However, the ability of both IL-2 and FCM to preserve viability was significantly associated with p24 negativity. Clinical and immunological follow-up was available for 60 patients for a mean period of 26 months. MR at the beginning of the study was significantly higher in the group of patients who clinically progressed (according to the CDC classification) or died during the follow-up (p < 0.0001). Our data suggest that MR correlates with both disease severity and progression and that MR is directly related to the depletion of CD4 cells in cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Hepatitis C virus-specific B cell activation: IgG and IgM detection in acute and chronic hepatitis C.

BACKGROUND/AIMS/METHODS: Immunological responses to hepatitis C virus infection have not been fully studied. In an attempt to clarify some immunopathogenetic aspects of B cell activation during acute and chronic hepatitis C virus infection and to identify markers of chronicity or of recovery, the humoral response in hepatitis C virus-infected patients was studied. RESULTS: In children with acute jaundice, with negative markers of acute hepatitis A, B and E, six of 87 (6.9%) had detectable anti-HCV IgM, and only one (1.1%) had detectable anti-HCV IgG. In adults with acute jaundice, with negative markers of acute hepatitis A, B and E, ten of 23 (43.5%) had detectable anti-HCV IgM associated in eight patients with detectable anti-HCV IgG. In chronic hepatitis C virus-infected adult patients, all anti-HCV IgG seropositive, four of 14 (28%) patients had detectable HCV-IgM in serum. In vitro specific antibody production was inducible in a minority of patients. In acute and chronic hepatitis C virus-infection, IgM-HCV serology did not correlate with viremia as detected by polymerase chain reaction. CONCLUSIONS: Therefore, the polymerase chain reaction remains at the moment the only direct marker to demonstrate hepatitis C virus viral replication in patients with acute and chronic hepatitis while anti-HCV IgM analysis alone has only a limited diagnostic value in hepatitis C virus-infection.

Acute Disease↗
PubMed1995

Immunodeficiency with hyperimmunoglobulinemia M in two female patients is not associated with abnormalities of CD40 or CD40 ligand expression.

The immunologic defect in X-linked immunodeficiency and hyperimmunoglobulinemia M (HIM) are related to defective expression of the CD40 ligand (CD40L). We have studied two female patients with HIM to evaluate the role of CD40/CD40L in the pathogenesis of impaired immunoglobulin switching. In addition to recurrent infections characteristic of humoral immunodeficiencies, the two patients had chronic hepatitis caused by type C virus. Phenotypic characterization of peripheral blood mononuclear cells showed a similar picture in both patients, with a reduction in the absolute numbers of CD4 cells and increased numbers of CD8 and CD3/DR cells. B cells (CD19+) were reduced in one patient, but CD40 was expressed on all CD19+ cells in both patients. The expression of CD40L was normal on peripheral blood mononuclear cells from the two patients with HIM on both resting and stimulated cells. The combination of anti-CD40 and cytokines (interleukin-2, interleukin-4, and interleukin-10) was able to restore proliferative capacity to anti-IgM. Peripheral blood mononuclear cells from the two patients with HIM showed a high spontaneous production of IgM in vitro and no production of IgG or IgE. Our data suggest that the defect of isotype switching in female patients with HIM is not related to defective expression of the CD40/CD40L receptor system. A possible role for chronic hepatitis C virus infection in the pathogenesis of the disease is suggested by the detection of specific production of anti-hepatitis C virus IgM.

Adolescent↗
PubMed1995

Seroprevalence of HIV and HCV infections in Alexandria, Egypt.

During the years 1992-1994, we tested 948 individuals from different population groups for HIV-1 and HIV-2 infections by ELISA and WB and for HCV infection by ELISA. Repeated ELISA reactivity for HIV was found in 2.12% of blood donors, 2.95% of fire brigade personnel and 1.61% of prisoners. Western blotting studies, however, showed that these samples were non-reactive or indeterminate to either HIV-1 or HIV-2. In contrast, anti-HCV antibodies were detected in 39% of fire brigade personnel, 31.4% of prisoners and 20.8% of blood donors. The analysis of risk factors for acquiring HCV infection showed a strong association between a past history of parenteral therapy for schistosomiasis and anti-HCV seropositivity (p < 0.0001). The implementation of preventive strategies is at the moment the mandatory choice to stop a further spread of the HCV infection. Meanwhile the same preventive measures could avoid spreading of the HIV disease.

Adult↗