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Biomedical subjects

C Trepo

Publications and source records attributed to C Trepo.

At least 181 records · Page 10Linked to original sources

[Liver damage induced by the ingestion of a product of phytotherapy containing wild germander. Four cases].

We report 4 cases of patients who developed hepatic injury during administration of herbal medicines for loosing weight with Wild Germander. Three developed jaundice and one had fatigue. Aminotransaminase activities were increased in all patients. Outcome was favorable after drug withdrawal in all patients. Liver biopsy showed centrolobular necrosis and portal lymphoplasmocytic infiltration. Another drug than Wild Germander might have been implicated in hepatic injury in two patients. The similarity of these cases suggests, however, that Wild Germander, like other herbal medicines, may be responsible for hepatic injury.

Acute Disease↗

HIV detection in culture of peripheral blood mononuclear cells: a relevant in vitro correlate of the antiviral effect of ZDV in vivo.

To better assess the antiviral effect of zidovudine (ZDV) in vivo and understand its limitations, we have studied human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cell (PBMC) cultures from 25 ZDV-treated patients and 20 untreated controls. Three months after initiation of therapy, 9 of the 25 treated cases became negative for HIV isolation (36%). Untreated cases never converted to a negative culture. In patients treated by ZDV and who remained culture positive, the kinetics of HIV replication in PBMC culture was found to vary with time. A statistically significant delay in the production of HIV in PBMC cultures from treated cases could be demonstrated after 3 months of ZDV therapy, when compared with untreated patients. By contrast, in such untreated patients the time required to reach the peak of reverse transcriptase activity in culture decreased during the follow-up period. These changes of in vitro HIV replication kinetics as well as the change to negative culture during ZDV therapy probably reflected the reduction of the number of infected cells in vivo. These results as well as the decrease of p24 antigenemia do indicate that ZDV indeed inhibits HIV replication in vivo. However, the effect of ZDV on HIV replication kinetics in PBMC fails to reach significance at 6 months, suggesting that the antiviral effect of ZDV may decrease over time. Our results suggest that ZDV is most effective when the intensity of HIV replication in vivo is still low.

Cells, Cultured↗

Acquired protein S deficiency: correlation with advanced disease in HIV-1-infected patients.

A plasma free protein S deficiency was detected in 41 of 63 patients infected with the human immunodeficiency virus type I (HIV-1). This study consisted in a prospective analysis of blood samples from 26 patients with confirmed diagnosis of AIDS, two with AIDS-related complex, 10 with polyadenopathy, and 25 who were asymptomatic. Protein S levels were compared to a matched control group of 24 healthy subjects. A deep venous thrombosis occurred in three AIDS patients with free protein S deficiency. A significant decrease in plasma free protein S levels was observed in HIV-1-seropositive patients (mean +/- SD, 56.5 +/- 23.3%) as compared with control subjects (105.3 +/- 18%, p = 0.0001). Free protein S levels were significantly lower in patients with full-blown AIDS (37.6 +/- 12.3%) than in patients without AIDS (69.8 +/- 19.9%, p = 0.0001). Low plasma free protein S levels correlated with high beta 2-microglobulin values (p = 0.0001), low CD4+ T-cell counts (p = 0.0002) and elevated urinary neopterin concentrations (p = 0.005). According to a multiple regression analysis, the progression to stages IVB, IVC1 or IVD of the Centers for Disease Control (CDC) appeared to be the main explanatory variable in free protein S-deficient patients. Such results suggest that free protein S deficiency may coincide with the development of AIDS. This could contribute to hypercoagulability and, in some instances, thromboembolic complications in AIDS patients.

Acquired Immunodeficiency Syndrome↗

Correlation between HBV DNA detection by polymerase chain reaction and Pre-S1 antigenemia in symptomatic and asymptomatic hepatitis B virus infections.

The presence of hepatitis B virus (HBV) genome in sera from 73 symptomatic and asymptomatic HBsAg carriers was studied by the polymerase chain reaction (PCR) with primers specific for the S and C regions. Pre-S proteins of the HBV envelope were detected in serum by a specific monoclonal antibody in a double immunoradiometric assay. Out of twenty-five symptomatic patients with chronic active hepatitis (14 with HBeAg and 11 with anti-HBe), all were positive for HBV DNA by PCR, while 14/14 HBeAg and 2/11 (18%) of the anti-HBe patients were positive by dot blot hybridization. All but one anti-HBe patient (96%) carried Pre-S1 proteins. Among the asymptomatic HBsAg carriers, HBV DNA was detected by PCR in 14/14 (100%) HBeAg positive patients and in 25/34 (73%) anti-HBe positive patients. Pre-S1 proteins were found, respectively, in 14/14 (100%) and 11/22 (50%) of the same cases tested in parallel. The 20 healthy blood donors devoid of HBV markers and with normal transaminases tested were found negative for HBV DNA using PCR. Out of 12 patients who recovered from acute hepatitis B, all were found negative by PCR analysis after a mean follow up of 1 year after seroconversion to anti-HBs. When serial samples from 2 patients (one with acute hepatitis B, the other with chronic hepatitis B) were tested for the presence of HBV DNA and of Pre-S1 proteins, both markers showed parallel development.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

In vivo neutralization of duck hepatitis B virus by antibodies specific to the N-terminal portion of pre-S protein.

The neutralization of duck hepatitis B virus (DHBV) infection using antibodies directed against the N-terminal portion of the large surface protein was examined in vitro and in vivo. We demonstrate here that a monoclonal antibody, directed against an epitope mapped between aa 77 and aa 100 on the DHBV pre-S, exerts a similar neutralizing activity (77%) both in vivo and in vitro. Furthermore, we have found that a polyclonal antiserum raised against the bacterially expressed 131 first amino acids of the DHBV pre-S region abolished the infectivity of DHBV in ducklings. Therefore, antibodies against a peptide representing most of the DHBV pre-S region (1-131) or a monoclonal antibody specific to an epitope within this region neutralizes in vivo DHBV infectivity.

Animals↗

Expression of HLA antigens and T cell infiltrates in chronic viral hepatitis. A comparison of biopsy and fine-needle aspiration findings.

To evaluate the expression of hepatocyte HLA Class I and II antigens and the infiltration of CD8-positive lymphocytes in patients with chronic hepatitis, cells obtained by the technique of fine-needle aspiration were compared with those obtained by percutaneous liver biopsy. In general, correlation between cytological and histological specimens of HLA Class I and Class II antigen expression and CD8 lymphocyte infiltration was excellent when comparing results of the core biopsy expressed semiquantitatively, and results from fine-needle aspiration quantitatively as percentage of cells stained. Although the major potential of multiple fine-needle aspiration sampling probably will be in the surveillance of patients who have received orthotopic liver transplants, the results of this study indicate that fine-needle aspiration can provide a useful technique for following antigen expression and inflammatory changes in studies in which frequent periodic samples may be necessary to monitor efficacy or toxicity of treatment regimens.

Biopsy↗

[Practical approach to the discovery of serum markers for infection by hepatitis B virus (HBs antigen or anti HBc antibody). Hypertransaminasemia or the two anomalies in a blood donor].

By now in France HBV seric markers (Ag HBs and Ac HBc) and transaminases level (ALT) screenings are compulsory by law in blood donors. People whose blood donation is discarded should be informed. A clinical, epidemiological and virological survey of such donors is required to differentiate healthy Ag HBs carriers and patients suffering from hepatitis B (who may eventually be treated). Similar guidelines may be recommended for the blood donors presenting high transaminases level without HBV seric markers in order to find a cause for such impaired biochemical tests: overweight, alcohol, drug consumption, auto-immune liver disease, genetic disorder, Non-A, Non-B, Non-C hepatitis....

Alanine Transaminase↗

Detection of polyadenylated RNA in hepatitis B virus-infected peripheral blood mononuclear cells by polymerase chain reaction.

Polymerase chain reaction (PCR) with a reverse transcriptase step characterized a specific transcription activity in hepatitis B virus (HBV)-infected peripheral blood mononuclear cells (PBMC) in two patients (1 and 2) with chronic hepatitis positive for antibody to hepatitis B core antigen (HBc). Patient 1 was also coinfected with human hepatitis delta virus. A patient who cleared HBV replication after antiviral treatment with vidarabine served as negative control. HBV-specific RNA poly A sequences were detected by PCR in PBMC of patients 1 and 2 even without detectable HBV DNA (patient 2) as shown by dot blot and PCR assays. RNA sequences were found in both the nucleus and cytoplasm. The demonstration of HBV mRNA sequences within PBMC suggests the transcription of viral DNA, in agreement with the findings of HBV surface antigen in PBMC. The results in patient 1 demonstrated HBV mRNA sequences in leukocytes even without PCR-detectable HBV DNA sequences, likely due to ongoing hepatitis delta virus replication.

Base Sequence↗

Plasma viraemia as a marker of viral replication in HIV-infected individuals.

Two hundred and twenty-eight blood samples from 154 HIV-seropositive subjects were investigated for the presence of HIV in peripheral blood mononuclear cells (PBMC) and plasma (without prior ultracentrifugation or filtration), using normal PBMC as the target for replication. HIV was recovered from PBMC and plasma in 80.5 and 19.5% of the patients, respectively. Plasma viraemia was significantly associated with clinical manifestations of HIV infection, indicating that HIV replication increased as disease progressed. This was confirmed by the statistically significant correlations between plasma viraemia and low CD4 cell counts (P less than 0.01) and low anti-p24 antibody titers (P less than 0.01). On patient follow-up, detection of HIV in plasma was transient. p24 antigenaemia was only detected in 13.6% of cases and was also associated with advanced clinical stages of the disease. When HIV RNA detection by polymerase chain reaction (PCR) was compared with plasma viraemia, HIV RNA was detected in plasma in all symptomatic cases and in 53.8% (seven out of 13) of asymptomatic patients [Centers for Disease Control (CDC) stages II and III], confirming that PCR was far more sensitive than plasma culture. These results indicate that cell-free virus production is associated with the clinical stage of HIV infection and may serve as a marker for disease progression. Detection of HIV RNA by PCR appears to be the most sensitive method to detect viraemia.

AIDS-Related Complex↗

Natural and experimental infection of wild mallard ducks with duck hepatitis B virus.

Wild duck populations were investigated over a 4 year period for duck hepatitis B virus (DHBV) infection and liver disease. It appeared that DHBV is endemic in wild migratory mallards from France and the U.S.A., although neither hepatocellular carcinoma nor viral DNA integration could be detected in liver samples examined. The follow up of natural infection indicated that wild mallards developed significantly higher serum titres to DHBV DNA than Pekin ducks. The results of experimental transmission demonstrated that such differences in viraemia were not related to the breed of ducks but to the virus isolate, since the wild mallard-isolated DHBV (DHBV WM) induced significantly higher viraemia in both mallard and Pekin ducklings compared to the domestic Pekin DHBV (DHBVP) isolate. The naturally infected mallard and Pekin ducks had only minor histological lesions of the liver compared with experimentally infected birds. There was no correlation between the intensity of viraemia and the severity of liver lesions, suggesting that as for mammalian hepadnaviruses the hepatic injury in DHBV-infected ducks is probably immunologically mediated.

Animals↗

Detection of human immunodeficiency virus-DNA and RNA in the skin of HIV-infected patients using the polymerase chain reaction.

The presence of HIV genomic-associated nucleic acids (DNA and RNA) within biopsies of normal-appearing skin and various skin lesions obtained from a group of 33 HIV-infected patients was investigated by using the polymerase chain reaction (PCR). In order to define the localization (dermal vs. epidermal) of HIV, the PCR was carried out separately on the dermis and the epidermis in 21 of the specimens. Altogether, HIV-DNA and HIV-RNA were detected, respectively, in 89% and 47% of the specimens included in this study; both DNA and RNA were detected more frequently in the dermis (90% and 43%, respectively) than in the epidermis (62% and 5%, respectively). No correlation could be established between the presence of HIV genomic material, the nature (normal-appearing vs. diseased) of the skin specimen studied, and the clinical or biologic severity of HIV infection, as evidenced by the CDC stage classification and the number of peripheral CD4+ cells. It seems, therefore, that the HIV is very frequently present within the skin during the course of HIV infection; however, its precise cellular localization and pathologic significance await further investigation.

Adult↗

Functional epitope analysis of the human CD11a/CD18 molecule (LFA-1, lymphocyte function-associated antigen 1) involved in HIV-1-induced syncytium formation.

After binding to the CD4 receptor, the human immunodeficiency virus 1 (HIV-1) may enter the T cell and induce the formation of multinucleated giant cells (syncytia). As well as the CD4 molecule, other molecules, such as the lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18) have been shown to be involved in HIV-1-mediated cell fusion. This study was designed to define regions on the human CD11a/CD18 molecule important for the HIV-1-induced syncytium formation. A CD11a/CD18 MoAb panel discriminating at least five distinct and spatially distant domains on the LFA-1 molecule was used. Comparison of the functional activity of different MoAbs demonstrated that all epitopes of the LFA-1 molecule were not of equal importance in HIV-1-induced syncytium formation between H9.III cells chronically infected with HIV-1 and uninfected CD4+ SupT1 cells. We also demonstrated that CD11a/CD18 MoAbs inhibit syncytia formation only at the level of the uninfected SupT1 cells, suggesting that the LFA-1 molecule expressed on SupT1 cells interacts with ligand(s) expressed on the infected H9.III cells. Two potential LFA-1 receptors on the H9.III cells were tested: the ICAM-1 molecule (intercellular adhesion molecule 1, CD54) and the HIV-1 transmembrane glycoprotein 41 (gp41). A CD54 MoAb (84H10) partially inhibited syncytia formation, thus demonstrating the involvement of the ICAM-1 molecule in the HIV-1-mediated cell fusion. However, the CD11a/CD18 MoAbs do not inhibit binding of the viral envelope glycoprotein gp41 to the cell surface, irrespective of the MoAb concentration used. Although we have not been successful in identifying all candidate fusion receptors for the LFA-1 molecule, these data suggest that some LFA-1 regions are important for syncytium formation and, therefore, in the cell-to-cell transmission of virus and in the spread of infection.

Acquired Immunodeficiency Syndrome↗

Comparison of HIV detection by virus isolation in lymphocyte cultures and molecular amplification of HIV DNA and RNA by PCR in offspring of seropositive mothers.

An early and accurate diagnosis of HIV infection is needed in the offspring of seropositive mothers. To this end, we have used two techniques for the direct detection of HIV in 12 newborns tested within 2 weeks after birth and 12 children. HIV isolation was carried out in lymphocyte cocultures and compared with detection of DNA and RNA sequences by molecular amplification using the polymerase chain reaction (PCR). In lymphocyte cocultures, HIV was isolated in 8 of 24 cases (33%), including 3 newborns, 3 symptomatic children, and 2 asymptomatic ones. HIV DNA was detected by PCR in twice as many cases, i.e., in 16/24 cases (66%), including 7/12 newborns, 4/4 symptomatic children, and 5/8 asymptomatic ones, 2 of whom became seronegative, HIV RNA was detected in 10 of 16 cases (60%) with detectable HIV DNA, including all of the cases who had a positive HIV isolation. Only children with clinical or biological signs of HIV infection were positive for HIV RNA. Furthermore, signs of HIV infection appeared within 6 months in three of the four newborns who were positive for HIV RNA at birth. These results indicate that HIV DNA detection by PCR is far more sensitive than HIV isolation in culture for the early diagnosis of HIV infection in offspring of seropositive mothers. HIV RNA detection appears to be a useful prognostic marker since it does correlate with disease progression and may serve as a clue for HIV replication in vivo.

Cells, Cultured↗

Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours.

The recent finding of c-myc activation by insertion of woodchuck hepatitis virus DNA in two independent hepatocellular carcinoma has given support to the hypothesis that integration of hepatitis B viruses into the host genome, observed in most human and woodchuck liver tumours, might contribute to oncogenesis. We report here high frequency of woodchuck hepatitis virus DNA integrations in two newly identified N-myc genes: N-myc1, the homologue of known mammalian N-myc genes, and N-myc2, an intronless 'complementary DNA gene' or 'retroposon' that has retained extensive coding and transforming homology with N-myc. N-myc2 is totally silent in normal liver, but is overexpressed without genetic rearrangements in most liver tumours. Moreover, viral integrations occur within either N-myc1 or N-myc2 in about 20% of the tumours, giving rise to chimaeric messenger RNAs in which the 3' untranslated region of N-myc was replaced by woodchuck hepatitis virus sequences encompassing the viral enhancer. Insertion sites were clustered in a short sequence of the third exon that coincides with a retroviral integration hotspot within the murine N-myc gene, recently described in T-cell lymphomas induced by murine leukaemia virus. Thus, comparable mechanisms, leading to deregulated expression of N-myc genes, may operate in the development of tumours induced either by hepatitis virus or by nonacute retroviruses in rodents. Activation of myc genes by insertion of hepadnavirus DNA now emerges as a common event in the genesis of woodchuck hepatocellular carcinoma.

Amino Acid Sequence↗