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Biomedical subjects

C Trepo

Publications and source records attributed to C Trepo.

At least 217 records · Page 12Linked to original sources

[Virus and insulin-dependent diabetes mellitus. Etiopathogenic perspectives].

Epidemiologic studies suggest an association between insulin dependent diabetes mellitus and viral infections. Several candidates like cytomegalovirus, Coxsackie virus and hepatitis virus have a selective tropism for beta cells. Progress in the understanding of the pathogenic importance of such viruses has been facilitated by animal models with virus induced diabetes and infections of human pancreatic beta cells maintained in culture. Immunological studies of type I diabetes after viral infections suggest that virus may trigger pancreatic autoimmunity. Molecular mimicry between viral and tissue antigens may represent a possible mechanism. Loss of immune tolerance toward beta cells would only appear in genetically predisposed individuals. The better understanding of the pathogenesis of type I diabetes mellitus brings out new approaches to treatment.

Animals↗

Unexpected low prevalence of delta antibodies in the east Amazon region and São Paulo: evidence for regional differences in the epidemiology of delta hepatitis virus within Brazil.

Antibodies (anti-HD) to hepatitis delta virus (HDV) were tested by radioimmunoassay in 207 human serum samples from the eastern Amazon (states of Pará and Amapá) and São Paulo, Brazil. 42 Amazon HBsAg asymptomatic carriers were negative for anti-HD. 84 São Paulo HBsAg asymptomatic carriers were also negative. Among the 81 HBsAg patients from São Paulo with different liver diseases, only one had anti-HD. Liver biopsy of this chronic active hepatitis case was positive for HBsAg, HBcAg and HDAg in liver, by an immunoperoxidase technique. The low prevalence of HDV infections in São Paulo and eastern Amazon was unexpected and contrasts with the recent reports of high prevalence in the western Amazon region. Such regional differences emphasize the need for extensive and precise worldwide epidemiological studies of HDV.

Adult↗

Delta superinfection in patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in a Sahelian area. Study of 112 cases versus 46 controls.

From October 1982 to June 1985 158 hospitalized patients in the National Hospital of Niamey, Republic of Niger, were selected whenever one of the following signs was found: hepatomegaly, jaundice, ascites, oesophageal varices, abdominal venous pattern, or splenomegaly. Investigations included hepatic echography (158/158), needle liver biopsy (68/158), radioimmunoassays for serum hepatitis B surface antigen (HBsAg; 158/158), anti-HBs (152/158), anti-HBc (129/158) and anti-delta antibody (anti-HD; 158/158). 112 patients with liver diseases comprised 28 with chronic hepatitis, 55 with non-alcoholic hepatic cirrhosis, and 29 with hepatocellular carcinoma (HCC). 46 patients with other diagnoses were used as controls. 71/112 liver disease patients were positive for HBsAg in serum compared with 1/46 controls (P less than 10(-9)). Prevalences of delta superinfection in patients with serum HBsAg (+) and anti-HD (+) were 45/112 (40.2%) in liver disease patients versus 1/46 (2.2%) in controls (P less than 10(-9)). Delta superinfection was very frequent in chronic hepatitis (8/28), non-alcoholic cirrhosis (24/55) and HCC (14/29). In chronic hepatitis, delta superinfection was more frequent in the chronic active form than in the chronic persistent type (not significant). Cirrhosis patients with delta superinfection were younger (10 years in males, 11 years in females) than those without (P less than 0.05).

Adolescent↗

Prevalence and significance of hepatitis B virus antigens: expression in peripheral blood mononuclear cells in chronic active hepatitis.

One-hundred four chronic active hepatitis (CAH) patients were investigated for the expression of the hepatitis B virus (HBV) surface and core gene products (HBs Ag, HBc/HBe Ags) in peripheral blood mononuclear cells (PBMC). Two-thirds of 59 HBs antigenemic patients expressed HBs Ag in PBMC but 26% of cases positive for both anti-HBs and anti-HBc also expressed HBs Ag while none of the controls reacted. Among HBs antigenemic patients, only those who replicated HBV express the core gene products (HBc and/or HBe Ag) in PBMC, and high replicators did so more often than low replicators (P less than 0.05). The HBs Ag prevalence in PBMC, although slightly higher among HBe Ag/DNAp-positive cases could not be correlated with the intensity of HBV replication. In 16 cases (8 replicants and 8 nonreplicants) HBV DNA was detected by DNA hybridization spot test, while 8 controls devoid of HBV markers were negative. Both T and non-T cells reacted similarly for antigenic or genomic HBV markers. When the expression of HBV gene products in PBMC among 43 cases with HBs antigenemia was compared with that in the liver, a good correlation was found in 70% of cases for HBs Ag but in only 40% for HBc and HBe Ags. By contrast, among 38 cases lacking HBs Ag in the serum but positive for anti-HBc with or without anti-HBs, concordance between liver and PBMC expression of core gene products (69%) was better than for HBs antigenemic patients (40%). These data suggest that PBMC including T lymphocytes may represent the second-best HBV target and may mimic the steps of HBV cycle within hepatocytes.

Adult↗

High affinity human monoclonal antibodies directed against hepatitis B surface antigen.

Peripheral blood mononuclear cells from donors immunized with hepatitis B vaccine (Pasteur Hevac B) were transformed with Epstein-Barr virus. Two polyclonal cell lines, producing antibodies to hepatitis B surface antigen were established and cloned. Seven clones were isolated; they secreted between 10 and 20 micrograms/ml of HBs specific IgG1 kappa or lambda antibody with anti-HBs titer of 300-800 IU/ml. These human antibodies expressed the anti 'a' specificities and had high affinity and avidity; their potential use as reagents for hepatitis B virus detection and for passive immunotherapy is under study.

Antibodies, Monoclonal↗

Main properties of duck hepatitis B virus DNA polymerase: comparison with the human and woodchuck hepatitis B virus DNA polymerases.

The main properties of the duck hepatitis B virus (DHBV) DNA polymerase have been studied and compared with those of the human hepatitis B virus (HBV) and of the woodchuck hepatitis virus (WHV) DNA polymerases. All 3 enzymes are active under high salt conditions in the presence of high magnesium concentration. DHBV DNA polymerase was found less sensitive to ethanol and to operate at higher optimal pH than the HBV and WHV DNA polymerases. Like the other two viral endogenous DNA polymerases, the DHBV enzyme was strongly inhibited by phosphonoformic acid but not by aphidicolin, sulfhydryl group blockers or phosphonoacetic acid. Inhibition of DHBV DNA polymerase by the triphosphate derivatives of several nucleoside analogs appeared similar to that reported for HBV or WHV endogenous polymerase. FIACTP was the most, and ACVTP the least effective inhibitor; BVdUTP was of intermediary potency; araCTP and araTTP had a greater inhibitory effect on DHBV DNA polymerase than HBV or WHV DNA polymerase. The similarities in the properties of DHBV and HBV DNA polymerase justify the use of the duck hepatitis B polymerase model for screening and evaluation of potentially active drugs against HBV infection.

Animals↗

Maintenance of woodchuck hepatitis virus activity in woodchuck hepatocyte primary culture.

Primary cultures of non-proliferating hepatocytes isolated by the two-step collagenase perfusion method from woodchuck naturally infected with hepatitis virus (WHV) were used to study WHV propagation in vitro. Hepatocytes carrying WHV DNA exhibited a very high level of survival and retained their morphological characteristics for 2 to 3 months. Over this time, they were found to produce virus-specific proteins and release viral particles with DNA polymerase activity into the medium. Using Southern blot analysis and a recombinant hepatitis B virus DNA plasmid probe, intracellular and extracellular viral DNA was consistently detected. Only extrachromosomal forms of WHV DNA were observed and no integration could be demonstrated in the DNA of the cells. The WHV DNA patterns were repeatedly identical with a characteristic smear starting from 3.3 kb associated with other smaller DNA fragments which presumably represented intermediate replicative forms of viral DNA. Furthermore, dot blot hybridization of the total RNA revealed the presence of WHV-specific transcripts in cells after 3 weeks of culture. All these results are compatible with the maintenance of active WHV replication in vitro although it was somewhat reduced after the first day of culture. This provides a mammalian model for hepadnavirus replication studies in stable primary hepatocyte cultures.

Animals↗

[Satellite vasculitis of B or non-A non-B hepatitis. Diagnostic value of a provocation test by intradermal injection of histamine].

The histo-pathological lesions of hypersensitivity vasculitis (HV) consist in an inflammatory reaction to circulating immune complexes deposited on the vascular endothelium. A provocation test by intradermal injection of histamine was used to demonstrate HV in patients with chronic hepatitis. Three groups of patients were studied: 16 with chronic hepatitis and HV, 22 with chronic hepatitis without HV, 4 control subjects. Skin biopsy was performed before and 3 hours after intradermal histamine. The following markers were looked for in the serum, skin and liver of all patients with chronic hepatitis: HBV (HBs Ag and HBe Ag, anti-HBs, anti-HBe and anti-HBc in the serum, HBs and HBc Ag in the liver); non-A non-B (non-A, non-B Ag and antibody, anti non-A non-Bc in the serum, non-A, non-Bc Ag in the liver). Viral antigens were found in healthy skin in 2 cases (1 chronic A hepatitis, 1 vasculitis), and after injection of histamine in 9 cases (4 chronic A hepatitis, 5 vasculitis). Viral antigens were found on skin biopsy in 2 patients with negative sera. Significant skin changes after histamine were detected only in HV (75 p. 100) even in the absence of cutaneous vasculitis (6/12 positive cases). An intradermal histamine provocation test is a simple, non-invasive method for diagnosing HV.

Hepatitis, Chronic↗

Pharmacokinetics of isoxicam in hepatic disease.

1 The pharmacokinetics of single and repeated oral doses of isoxicam, an extensively metabolized drug, were studied in patients with compensated and decompensated hepatic disease. 2 After a single oral dose, isoxicam was slowly absorbed and eliminated (half-life ranging from 10.5 to 53.9 h). Its pharmacokinetics did not differ from those observed in healthy volunteers and were not significantly influenced by the severity of hepatic disease. However, the t1/2 of isoxicam was found to be inversely (r = -0.700, P less than 0.05 n = 14) related to the log gamma-glutamyl transpeptidase plasma activity. 3 During chronic oral treatment in patients with compensated hepatic insufficiency, steady-state was achieved after 7-9 days of therapy. The mean elimination half-life of isoxicam in five patients was 42.6 +/- 4.5 h, a value which was not statistically different from that obtained in the single dose study. 4 It was concluded that patients with hepatic insufficiency do not require a systematic modification of drug dosage but that long-term treatment should be employed with caution in these patients.

Adult↗

Serial transmission of a human non A-non B hepatitis viral strain to HBV-protected chimpanzees: successive histological and ultrastructural studies.

A NANB agent of human origin was inoculated in HBV-immunized chimpanzees. Infection was proven in two animals and serially passed to two others. The absence of anti-HBc in serum and the absence of HBsAg and HbcAg in liver are arguments against the HBV nature of the transmitted infection. Moreover, the reproducible appearance of the NANBcAg/Ab system at each passage from man to chimpanzee and from chimpanzee to chimpanzee, a response not elicited in control animals, suggests that this reaction may be a specific immunologic marker for the strain. NANB infection was transmitted in all chimpanzees. Distinctive hepatic morphologic features were obtained in the liver biopsies of the human donor and the inoculated chimpanzees: eosinophilic alterations of hepatocytes and numerous inflammatory cells. Inflammation was more prominent than necrosis, appearing earlier and lasting longer, but was not topographically close to the eosinophilic changes. On electron microscopy, particles characteristic of NANB agent were observed in the cytoplasm of the hepatocytes. No particles were demonstrated in the nucleus of these cells.

Animals↗

[Eradication of hepatitis B in dialysed patients through repeated sero vaccinations].

From December 1981 to April 1984, 56 dialysed patients have been enrolled in a sero-vaccination program in which injections of Hevac B vaccine and anti-HBs immunoglobulin have been repeated to obtain anti-HBs response. Anti-HBs antibodies were distinguished from passively transmitted anti-HBs whenever anti-HBs levels above 33 mUI/ml were found 60 days after the last injection of hepatitis B immune globulins (4 ml). Among 39 patients (25 men, 14 women) (mean age 59 years) the proportion of vaccine responders was 44%, 67%, 82%, 90% after respectively 4, 6, 10, 14 injections of Hevac B vaccine. Age, male sex and duration of dialysis were found to decrease the immune response to the vaccine. Multiple injections and maintenance of protective anti-HBs (titer greater than 20 mUI/ml) can be considered as the most effective method to eradicate HBV infection from dialysis centers.

Adult↗

Demonstration of anti-mitochondria antibodies by ELISA. Comparison with the indirect immunofluorescence technique on organ sections.

We determined the optimal conditions for the detection of anti-mitochondria antibodies by an enzyme linked immunosorbent assay (ELISA). Pig heart mitochondria was used at 5 mg/ml to coat polystyrene microplates and a serum dilution of 1/200 to carry out testing. This procedure detects anti-M1, M2, M4 and M6 antibodies and is more sensitive than indirect immunofluorescence. Anti-endoplasmic reticulum and anti-ribosome antibodies give negative results but anti-ds-DNA at high titres are a possible cause of false positivity.

Animals↗

[Plasma exchange and acyclovir in Behçet's disease].

It has been postulated that Behçet's disease may be a viral induced vasculitis. In the present study plasma exchanges were applied in an attempt to remove circulating immune complexes and restore cellular immunity. High doses of acyclovir were administered in association with plasma exchanges since it has been shown that herpes simplex virus type 1 might be involved in Behçet's vasculitis. Seven patients with severe ocular manifestations of Behçet's disease were selected for the study. Plasma exchanges were carried out at the rate of 3 per week during 3 weeks and then once every two weeks during 3 months followed by 1 per month during 3 months. 45 mg/day/kg acyclovir were administered intravenously for 21 days. At the end of the follow-up period comparative analysis of panretinal fluorescein angiographies before and after treatment showed no change of the fundus lesions in 3 patients, improvement in only 2 patients and significant worsening in 2 patients. The rather negative results of the present trial lead to assume that HSV-1 is not the virus involved, if any, in Behçet's disease. On the other hand, in the present study, the efficiency of plasma exchanges was transient.

Acyclovir↗