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Biomedical subjects

J Drucker

Publications and source records attributed to J Drucker.

At least 19 recordsLinked to original sources

[The vaccine against poliomyelitis, inactivated, concentrated, injectable: analysis of ten years of use in tropical countries].

A new inactivated poliovirus vaccine of enhanced potency (N-IPV) has been developed since the late 70's. N-IPV can be produced on a large scale in industrial tanks. N-IPV has been extensively studied on all continents and under different climates, specially in tropical countries. It is presently included in vaccination programs of several african regions. N-IPV is recommended in infants as soon as 6 to 8 weeks of age, following a schedule including a primary vaccination with 2 doses at 2 months interval. N-IPV is usually combined to DPT in a quadruple form (DPTPolio). The characteristics and performances of N-IPV make it a substitute or a complement to oral poliovirus vaccine for use in the Expanded Program on Immunization, specially in the perspective of the goal of global poliovirus eradication.

Antibodies, Viral

Hepatitis B virus antigens in human primary hepatocellular carcinoma tissues.

The presence of hepatitis B virus (HBV) antigens was examined in specimens of liver tissue obtained at necropsy from black Senegalese patients suffering from primary hepatocellular carcinoma (PHC). The results were correlated with markers of hepatitis B infection in serum. Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) were sought for in 15 liver extracts. HBsAg was found in the liver in 10 of 12 cases with HBsAg-positive serum. HBcAg was detected in three livers. The HBsAg was detected in seven of eight livers by immunofluorescence and orcein staining. HBsAg-positive cells were mainly located in the peri-tumoral cirrhotic tissue, although positive hepatocytes were also found in tumour nodules in liver from one of the patients. HBcAg was found in five of seven cases by immunofluorescence in hepatocytes of the cirrhotic areas. HBcAg fluorescence was primarily nuclear but, in some lobules, a patchy cytoplasmic fluorescence was observed. This suggests a cytoplasm-nucleus pathway in the synthesis of the HBV core antigen. Electron microscopy was performed on two HBsAg- and HBcAg-positive cases. Fibrillar and crystalline cytoplasmic inclusions were observed in tumour cells. In the same cells, 20-25 nm virus-like particles were present in swollen cisternae of the endoplasmic reticulum.

Adult

[Hepatitis A of children. Seroepidemiological study among French urban population (author's transl)].

A prevalence survey of hepatitis A antibody (anti-HAV) was conducted among 145 children living in the area of Tours (France). Thirty-four per cent of children's sera was found anti-HAV positive when tested by both immune adherence hemagglutination assay (IAHA) and specific radio-immunoassay (RIA). The prevalence of anti-HAV among infants less than one year and children between 1 to 5 years, was 35 per cent and 15 per cent respectively. From 6 years old, the prevalence of anti-HAV increased abruptly and reached 47 per cent in the 11 to 15 age group. Anti-HAV titers as measured by IAHA also increased according to age. In this study, the prevalence of anti-HAV was not related to sex, history of past surgery and/or blood transfusions. Only 12 per cent of children with anti-HAV positive test had history of jaundice. These results show that, in France, primary contact with hepatitis A virus (HAV) appear early in childhood, at school age, and that in children more than 80% of HAV infections remain asymptomatic.

Adolescent

Serologic response in human hepatitis A: detection of antibody by radioimmunoassay and immune adherence hemagglutination.

An indirect solid-phase radioimmunoassay (RIA) for detection of antibody to the hepatitis A antigen (anti-HAV) was developed using polystyrene pearls as the solid phase and hepatitis A antigen (HAAg) extracted from marmoset livers. This RIA was compared to an immune adherence hemagglutination assay (IAHA) which employed HAAg derived from the stools of chimpanzees collected during acute hepatitis A. Anti-HAV was detected in the sera of 15 humans with naturally acquired hepatitis A infection. Sensitivity and specificity were greater using the RIA, permitting the detection of anti-HAV as early as the time of onset of jaundice. Either seroconversion or a significant increase in the titer of anti-HAV was demonstrated following hepatitis A exposure in paired sera from six patients by both techniques. No significant difference in anti-HAV responses was noted between patients with icteric compared to anicteric hepatitis A or between children and adults with hepatitis A.

Adolescent

Simultaneous acute infections with hepatitis A and hepatitis B viruses in a chimpanzee.

The unexpected occurrence of a hepatitis B virus (HBV) infection in a chimpanzee experimentally inoculated with hepatitis A virus (HAV) provided an opportunity to examine the course of simultaneous acute infections with both agents. A chimpanzee inoculated intravenously with HAV developed elevated levels of aminotransferases in serum, detectable excretion of hepatitis A antigen in feces, and a marked antibody response to HAV. During the acute phase of this experimentally induced infection with HAV, the chimpanzee simultaneously developed an HBV infection. The latter was characterized by jaundice, a second increase in levels of aminotransferases in serum, and the appearance in serum of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, antibody to hepatitis B core antigen, and, later, antibody to HBsAg. During the acute phase of both HAV and HBV infections, marked histopathologic inflammatory changes were observed in serial liver biopsy specimens. In this chimpanzee, the concurrent acute infection with both HAV and HBV occurred in association with marked liver damage.

Acute Disease

Vaccine against hepatitis B--18 months prevention in a high risk setting.

The development of a vaccine against hepatitis B prepared with purified and inactivated HBs Ag is described. This vaccine has been applied in patients and staff members of haemodialysis centres. Safety and efficiency of the vaccine are very satisfactory. The response of patients to immunisation was significantly lower compared to the response of the staff members. None of the volunteers who had a primary response to immunisation developed signs of clinical or biological hepatitis.

Hepatitis B

HBsAg-negative chronic active hepatitis related to hepatitis B virus.

Numerous cases of chronic hepatitis have been shown to be closely associated with persistent infection with hepatitis B virus (HBV). A group of 100 patients suffering from chronic active hepatitis (CAH) was investigated for HBV serologic markers. Of these, 35 patients were HbsAg-positive; in 26 HBsAg-negative subjects, anti-HBc were detected using counterimmune electrophoresis and complement-fixation tests. These data suggest that chronic liver disease in patients who were only anti-HBc-positive might be related to persistent infection with hepatitis B virus. Epidemiological clinical and histopathological data were different when we compared CAH patients who were HBsAg-negative, but anti-HBc-positive, with HBsAg-positive CAH patients. A sequence is proposed leading from HBsAg-positive to HBsAg-negative CAH, cirrhosis, and hepatoma in temperate areas, according to a model similar to the one described in intertropical Africa.

Adolescent

Hepatitis B virus DNA in primary hepatocellular carcinoma tissue.

Tumour, cirrhotic, and metastatic tissues from four patients with primary hepatocellular carcinoma have been investigated for the presence of hepatitis B viral DNA by nucleic acid hybridization. Tumours from two of three patients with a current HBV infection contained 1--2 genomes per cell of unintegrated viral DNA, while tumours from the third HBs antigen-positive patient contained less than one genome equivalent per ten cells. A tumour from one patient with anti-HBs contained no detectable HBV DNA. A variety of models involving HBV as an etiologic agent may be advanced to explain the statistical correlation of HBV infection with primary hepatocellular carcinoma (PHC). The data presented here argue against the model that HBV DNA integrated into every cell is required to maintain the oncogenic transformation of hepatocytes, but they do not rule out other models.

Adult

Localization of hepatitis A antigen in marmoset organs during acute infection with hepatitis A virus.

Twelve marmosets (Saguinus mystax) were inoculated intravenously (iv) with hepatitis A virus (HAV). One died early (day 12); seven were sacrificed at the time of elevation in level of alanine aminotransferase (serum glutamic-pyruvic transaminase), and four without elevation were not sacrificed but seroconverted. In the seven marmosets sacrificed during the acute stage of illness, hepatitis A antigen (HA Ag) was detected in the liver by immunofluorescence in all cases, by immune electron microscopy in four, and by enzyme-linked immunosorbent assay (ELISA) in three. The HA Ag appeared by immunofluorescence as very fine granules in the cytoplasm of hepatocytes and Kupffer cells. The HA Ag could not be detected by immunofluorescence in biopsy specimens taken from the duodenum, jejunum, ileum, or transverse colon in any of eight marmosets in which necropsy was performed during the acute or preacute stage of illness. These findings suggest that the gut is not involved during the acute phase of HAV infection following iv inoculation into marmosets. The ELISA results showed that only three of 12 marmoset livers obtained during the acute phase of HAV infection could be used as an antigen source in serologic testing for antibody to HA Ag. Thus, marmoset livers were no better as a source of HA Ag than acute-phase stools from patients with type A hepatitis.

Acute Disease

Incidence and significance of hepatitis B e antigen and antibody in postnecrotic cirrhosis and primary hepatocellular carcinoma.

A study of the serological markers of Hepatitis B virus (HBV) including e antigen (HBe Ag) and antibody against HBe Ag (anti-HBe) was performed in Senegalese patients suffering from cirrhosis and primary hepatocellular carcinoma, and in a control group (blood donors). It was not possible to diagnose additional HBV infections in primary hepatocellular carcinoma patients using HBe Ag or anti-HBe Ab alone as serological markers. The lower prevalence of HBe Ag among primary hepatocellular carcinoma patients as compared with cirrhotic patients suggests that active replication of HBV becomes increasingly defective during the course of the malignant process.

Adult

Hepatitis B vaccine: efficacy in high-risk settings, a two-year study.

A formalin-treated hepatitis B vaccine in the form of purified hepatitis B surface antigen (HBsAg) was prepared from asymptomatic human HBsAg carriers. Its safety and potency were tested in 5 chimpanzees. The vaccine was administered to 264-individuals. The results of the first 173 immunizations--46 hemodialysis patients and 127 staff members--are presented. Potency was ascertained and efficacy assessed by the development of humoral immune responses to HBsAg (anti-HBs antibody) and seroepidemiologic studies of vaccinated and nonvaccinated subjects. The results, 2 years after immunization, suggest that the vaccine was protective against hepatitis B infection in high-risk hemodialysis settings. Preliminary studies with an inactivated hepatitis B vaccine similarly prepared, but with aluminum hydroxide as adjuvant, indicate that a such a preparation induces a more rapid and stronger anti-HBs response.

Adjuvants, Immunologic

Localization of hepatitis A antigen in liver tissue by peroxidase-conjugated antibody method: light and electron microscopic studies.

Hepatitis A antigen (HAAG) was localized in liver tissue from marmosets inoculated with human hepatitis A virus (HAV) by light and electron microscopy by using a peroxidase-conjugated antibody method. The fine granular peroxidase staining was scattered throughout the cytoplasm of liver cells when viewed with the light microscope. The distribution of HAAg-positive cells was focal. Virus-like particles, 24 to 27 nm in diameter, were observed in the cytoplasm of hepatocytes and smaller cells, resembling Kupffer cells, by standard thin-section electron microscopy (thin section EM). By immunoperoxidase electron microscopy (immunoperoxidase EM), HAAg was detected on the particles, which were aggregated within cytoplasmic vesicles of the hepatocyte. The surrounding membrane of the vesicles was also HAAg- positive. Similar HAAg particles were observed in the cytoplasm of smaller cells adjacent to hepatocytes as well. Thus, immunoperoxidase EM revealed that the 24- to 27-nm virus-like particles in the cytoplasm of liver cells obtained from marmosets were infected with HAV contained HAAg.

Animals

[Vaccination against hepatitis B in man].

The preparation of a vaccine against hepatitis B is described. The vaccine is prepared from the HB viral coat (HBs Ag) purified and formalin inactivated. The HBs Ag is isolated and purified from the blood of healthy HBs Ag positive donors by means of an immunoadsorbent technique. The inocuity and efficacy were tested on chimpanzees. Vaccination was then applied in an attempt to protect patients and ward staff in a high risk haemodialysis unit. The efficacy of the vaccine was assessed by humoral and cellular anti-HBs immune reactions. The study of HBs antigenaemia in vaccinated and non-vaccinated subjects indicate that this vaccine protects against hepatitis B. Many arguments are in favor of aetiological role of the hepatitis B virus in the genesis of primary liver cancer in tropical areas. Immunization against hepatitis B could be the first example of prevention of a potentially oncogenic viral infection.

Animals