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Biomedical subjects

M Comar

Publications and source records attributed to M Comar.

At least 19 recordsLinked to original sources
PubMed2006

The association of chronic hepatitis B and myopathy.

In two patients with chronic hepatitis B and myopathy, muscle biopsy showed necrosis and scarce inflammatory infiltrates. CD8+ cells surrounded some non-necrotic fibers. Hepatitis B virus (HBV) DNA and antigens were found inside intact muscle fibers. Major histocompatibility complex class I antigens were coexpressed with viral antigens. In one patient, symptoms improved during antiviral therapy. HBV can infect muscle fibers and an immune-mediated response to viral antigens may cause muscle injury.

Adult↗
PubMed2006

HPV genotyping and HLA II analysis in a pedigree study of pediatric RRP: preliminary results.

OBJECTIVE: This preliminary pedigree study aims at the evaluation of HPV infection and HLA class II alleles as predictive markers in pediatric RRP. METHODS: We investigated for HPV genotyping and HLA class II polymorphisms all the components of family nucleus where we detected a child born to an HPV infected mother and suffering from RRP. RESULTS: HPV 11 was detected both in the laryngeal biopsies of two of the three affected babies and in the cervical smear of their mothers. The third child was positive for HPV 6 while his mother harboured a double HPV 6-16 infection. In one family, the HLA-DQB1*0501 allele exerted its protective role. The HLA-DQB1*0301 allele, commonly associated to a high grade of cervical neoplasia and HPV infection, was present in homozygous in one mother and her child. The same allele was found, though in a heterozygous form, in the third patient too. CONCLUSION: Our report is the first attempt to use the pedigree study for the evaluation of HLA class II alleles and HPV infection related to pediatric RRP. This approach could identify genetic markers that may influence disease predisposition and the severity of HPV infection.

Alleles↗
PubMed2006

HBV, HCV, and TTV detection by in situ polymerase chain reaction could reveal occult infection in hepatocellular carcinoma: comparison with blood markers.

OBJECTIVE: To report a retrospective analysis on the presence of hepatitis B virus (HBV), hepatitis C virus (HCV), and transfusion transmitted virus (TTV) sequences in formalin fixed, paraffin embedded liver biopsies from eight patients with hepatocellular carcinoma, in comparison with blood markers. METHODS: A direct in situ polymerase chain reaction (PCR) technique was developed for the detection and localisation of genomic signals in the liver tissue. Conventional serological and molecular methods were used for blood evaluation. RESULTS: In situ PCR showed the presence of one of the three viruses (four HCV, two HBV, and one TTV) in seven of the eight patients. In addition, a co-infection with HBV and HCV was detected in one patient. HCV and HBV sequences were located in the cytoplasm and the nucleus, respectively. When compared with blood markers, these findings were compatible with one occult HBV and two occult HCV infections. CONCLUSIONS: These findings provide further evidence for occult HBV and HCV infections in cancerous tissues from patients with hepatocellular carcinomas. In situ PCR could be an additional tool for evaluating the viral aetiology of hepatocellular carcinoma alongside conventional diagnostic procedures.

Adult↗
PubMed2004

Three-year (1999-2002) of epidemiological and virological surveillance of influenza in north-east Italy.

The results of the epidemiological and virological surveillance of influenza performed during the 1999/2000, 2000/2001 and 2001/2002 seasons in the northeastern Italy were presented and the relationship between age-specific morbidity rates and circulating strains were discussed.The epidemiological findings pointed out a change in age distribution. During the 1999/2000 season, characterized by a circulation of viruses antigenically close to the vaccine strain, a similar incidence rate in the 0-14 and 15-64-year-old groups was observed, while during the 2001/ 2002 winter the virus infected mostly children. During 2001/2002 season, B type viruses predominated with at least three distinguishable molecular variants. In particular, B/Victoria/2/87-like viruses re-emerged after more than a decade, and the antibodies elicited by the vaccine strain and by the strains circulating in previous seasons were poor or not protecting. The accumulation of susceptible subjects in young age group during the 1990s, due to the lack of circulation of B/Victoria/2/87-like viruses, was responsible for the unusual morbidity in the 0-14 year group. No circulation of B/Victoria/2/87-like viruses was observed in > 64-year-old group during 2001/2002 epidemic, probably due to a long-lasting immunity against viruses belonging to this lineage.

Adolescent↗
PubMed2003

Seroprevalence of HTLV-I and HTLV-II infection among immigrants in northern Italy.

To assess the prevalence of human T cell leukemia virus type I (HTLV-I) and 2 (HTLV-II) infection and the associated risk factors among immigrants living in Northern Italy, we surveyed 3017 open-population subjects from three geographical areas and 371 prisoners. In the open population, the overall prevalence was 0.3% for HTLV-I and 0.1% for HTLV-II, while among prisoners, HTLV-I and HTLV-II infection were detected in 1.4 and 0.8% of subjects, respectively. HTLV-I prevalence was higher in subjects with multiple sexual partners or sexually transmitted diseases. This association was significant in the open-population group and close to significance in prisoners. Multivariate analysis showed that human immunodeficiency virus (HIV) seropositivity remained significantly associated with HTLV-I infection in both targeted populations (OR: 11.2 in the open population; OR: 9.9 among prisoners), whereas sexual exposure was associated with HTLV-I seropositivity only for prisoners (OR: 14.3). No independent variable was related to HTLV-II infection.

Adult↗
PubMed2002

In situ polymerase chain reaction detection of transfusion-transmitted virus in liver biopsy.

The potential role of transfusion-transmitted virus (TTV) infection in determining liver damage is poorly understood and no information exists about TTV replication within hepatocytes. In this study, we assess TTV in situ PCR in liver tissue. Twenty-one patients with different degrees of liver damage were studied by both serum TTV-DNA detection and in situ TTV PCR analysis and extractive PCR in liver biopsy paraffin sections (FFPE). Extractive PCR and in situ PCR detected TTV-DNA both in serum and liver tissue of five patients. The presence of TTV in serum matched with that found in the liver and TTV sequences were never found independently in liver or serum. Four out of five TTV-DNA-positive patients have not other known cause of liver damage while in one a coinfection from HCV was observed. Our data indicate that in situ PCR appears to be a reliable tool for the detection of TTV-DNA in FFPE, and may help detecting unknown origin of liver damage.

DNA Virus Infections↗
PubMed2001

Direct in situ PCR allows rapid and sensitive detection of high risk human papillomavirus in cytologic specimens and formalin-fixed paraffin tissues by fluorescent labelling.

We developed a rapid, sensitive and robust high risk human papillomavirus (HR HPV) detection protocol based on direct in situ PCR technology and fluorochrome-modified nucleotides on cytologic specimens (cell smears) and on HPV infected tissues (CIN III). Reproducible results on both cytologic specimens and paraffin-embedded tissues were obtained, providing a powerful tool for clinical investigation on HR HPV infection. Quantitative PCR performed on the same tissue sections adjacent to those used for in situ techniques allowed us to establish the sensitivity of our methods, able to detect rare copies (about 15 in our paraffin-embedded tissues) of HPV.

Female↗
PubMed2000

[Typification of HPV in clinical practice].

OBJECTIVE: To improve the sensitivity of cervical carcinoma screening and to determine the optimal management with an ASCUS Pap result we evaluated the effectiveness of combining thin layer cytologic slides (ThinPrep) and HPV DNA testing. METHODS: A total of 170 women were studied with conventional Pap smears, liquid based cytology, HPV testing and colposcopy with eventual histologic evaluation. RESULTS: The ThinPrep method yielded 12.5% more high grade lesions than did the conventional smears (and more severe diagnoses as compared to the conventional smears). HPV prevalence was significantly associated with disease status. Of 30 patients with ASCUS, HPV testing detected 100% of high grade lesions and 67% of low grade. If colposcopy had been limited to HPV+ women, 47% of case would have been spared. CONCLUSIONS: Liquid based cell collection improves sensitivity for the detection of disease. For women with ASCUS cytology, HPV DNA testing of residual specimen can identify the majority of high risk cases using a single sample.

Cervix Uteri↗
PubMed1999

Dynamics of provirus load and lymphocyte subsets after interleukin 2 treatment in HIV-infected patients.

The association of antiretroviral agents plus interleukin 2 (IL-2) represents an efficient approach to the treatment of HIV+ subjects. While the effects of IL-2 on the immune system have been investigated, little is known concerning its impact on HIV dynamics. Two antiretroviral drugs control HIV viremia, but have minimal effects on the proviral load, a predictor of disease progression and response to therapy. The aim of this study was to define the effect of rIL-2 on HIV proviral copy numbers and its relationship to changes in CD4+ and CD8+ subsets. Twelve HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous rIL-2, in combination with zidovudine and didanosine. This regimen resulted in a rapid and durable decrease in proviral load in the peripheral blood, in an increase in CD8+ lymphocytes, and in the emergence of a CD4+CD45RA+ T subset. These results demonstrate that the rationale for IL-2 administration to HIV+ patients may depend not only on its effects on the immune system, but also on the reduction of the number of infected cells, reinforcing the notion that IL-2 can have a favorable impact on the natural history of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Concomitant therapy with subcutaneous interleukin-2 and zidovudine plus didanosine in patients with early stage HIV infection.

A phase II study was performed to evaluate the feasibility and activity of subcutaneous (SC) interleukin-2 (IL-2) administration plus zidovudine (ZDV) and didanosine (ddI) in patients with early stage HIV infection. Between October 1995 and October 1996, 12 patients completed 6 cycles of the following scheduled therapy: ZDV plus ddI and SC self-administration of 6 mIU of IL-2 at days 1 to 5 and 8 to 12 of a 28-day cycle for a total of 6 cycles (24 weeks). After 6 cycles, patients received only ZDV plus ddI and they were observed up for an additional 24 weeks. Our schedule was well tolerated as an outpatient regimen and led to a significant elevation in CD4 count, which lasted for 24 weeks after the end of IL-2 therapy. Moreover, CD4/CD25, as well as CD4/CD45RO and CD4/CD45RA, cell levels were significantly increased at the end of the therapy and remained significantly elevated after 24 weeks. During the 6 cycles, HIV-associated viremia was significantly decreased and, accordingly, we observed a significant decline of proviral DNA in peripheral blood mononuclear cells (PBMCs). During follow-up, 10 of 12 treated patients continued to show levels of HIV-related viremia <500 copies/ml. Our results demonstrated that IL-2 and ZDV plus ddI is a well tolerated and effective therapy for patients with HIV in early stages of the disease.

Adult↗
PubMed1997

Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects.

HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-gamma; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45RA+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-gamma, RANTES, and sCD30 in HIV+ patients. 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA+/CD26+ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-gamma, and sCD30 were significantly upregulated. These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-gamma. These effects may be beneficial to HIV+ patients by improving their immune response to microorganisms or vaccines.

CD4 Lymphocyte Count↗
PubMed1997

Dynamics of HIV-1 mRNA expression in patients with long-term nonprogressive HIV-1 infection.

A large number of evidences indicate that progression of HIV disease is driven by an increase in viral burden. It is still unclear, however, to what extent this is contributed by the dysregulation of the molecular mechanisms governing virus gene expression at the transcriptional or posttranscriptional levels. To address this issue, several quantitative virologic parameters (including provirus transcriptional activity and splicing pattern) were analyzed in individuals with nonprogressive HIV infection and compared with those of a matched group of progressor patients. Exact quantification was achieved by a competitive PCR procedure using a multicompetitor template. Nonprogressors were characterized by striking differences in the levels of viremia, provirus copy number, and overall levels of all viral mRNA classes in peripheral blood mononuclear cells. Additionally, the transcriptional activity of the proviral DNA in these patients was mainly engaged in the production of multiprocessed transcripts, with a pattern resembling the early phases of the experimental infection. Taken together, these results show that both viral load and provirus transcription pattern are remarkably different in infected individuals nonprogressing toward overt disease, and further support the notion that disease progression is accompanied by a change in the kinetics of HIV gene expression.

Adult↗
PubMed1997

C-C chemokines released by lipopolysaccharide (LPS)-stimulated human macrophages suppress HIV-1 infection in both macrophages and T cells.

Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C-C chemokines (RANTES, MIP-1 alpha, and MIP-1 beta) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

Cells, Cultured↗
PubMed1996

The effects of antineoplastic chemotherapy on HIV disease.

Six patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma receiving chemotherapy (CT) with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus granulocyte colony-stimulating factor were sequentially monitored to study the effects of these treatments on their immunologic status (CD4 and CD8 cell counts) and on HIV plasma viremia. We show that mean CD4 cell counts declined significantly after the third cycle of CT (187 +/- 117/microliters before CT versus 92.4 +/- 60/microliters; p = 0.04) and remained significantly reduced 4 months after completion of CT. Modifications of CD8 cell counts were not statistically significant. The effects of CT on plasma viremia, as measured by a competitive polymerase chain reaction technique, were delayed until the fourth cycle, when an increase of viral load ranging from 0.6 to 2 logs (p = 0.027) was observed. After this point, viremia returned to baseline levels, with the exception of two patients who later developed opportunistic infections and one who underwent disease progression. These results suggest that, contrary to CD4 cell counts, plasma viremia could be a faithful surrogate marker for monitoring of HIV disease progression in patients undergoing CT.

Antineoplastic Agents↗