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Biomedical subjects

F Deinhardt

Publications and source records attributed to F Deinhardt.

At least 127 records · Page 7Linked to original sources

Production of interferon alpha and interferon gamma by peripheral blood leukocytes from patients with chronic hepatitis B virus infection.

Peripheral blood leukocytes from patients with chronic hepatitis B virus (HBV) infection were studied for their capacity to produce interferon (IFN) alpha or IFN gamma. Yields of IFN alpha in leukocyte cultures stimulated with influenza A virus or human leukemic cells were significantly lower than those obtained from healthy controls. Production of IFN gamma in response to induction with protein A of Staphylococcus aureus was also significantly diminished. Defects of IFN production in leukocyte cultures showed no correlation with active viral replication or the degree of severity of HBV-associated liver disease. The demonstration of partial defects of endogenous IFN production provides a rationale for using IFN replacement therapy in patients with chronic HBV infection.

Adolescent↗

Immune responses to late booster doses of hepatitis B vaccine.

Nineteen healthy young adults were vaccinated with plasma-derived hepatitis B vaccine at months 0, 1, and 12, and their immune responses were compared to those of a similar group of 20 vaccinees immunized at months 0, 1, and 6. Late booster injections at 12 months produced nearly fivefold higher geometric mean anti-HBs levels than those of the control group. The higher anti-HBs values may lead to longer persistence of anti-HBs and thus to longer protection against hepatitis B.

Adult↗

Detection of hepatitis B virus DNA in serum by a rapid filtration-hybridization assay.

A simple method for detecting hepatitis B virus DNA (HBV DNA) in serum using a filtration step for spotting sera on nitrocellulose paper followed by molecular hybridization is described. This method is rapid, sensitive, requires very small quantities of serum, and can be used for simultaneous testing of up to 96 samples in one filter apparatus. The sera tested for HBV DNA were also assayed for serological markers of HBV infection and comparison of data shows that on average 67% (30 of 45) of HBsAg- and HbeAg-positive sera contain HBV DNA, whereas 13% of HBsAg- and anti-HBe-positive sera contain HBV DNA. In general, there was a statistically significant correlation between the concentration of HBsAg in the serum and the presence or absence of HBV DNA. These results indicate that molecular hybridization is a valuable assay in addition to serological markers for identifying the possible infectivity of sera, and the simple and rapid method reported here makes the use of such hybridization technique easier.

DNA, Viral↗

What's new in hepatitis delta virus?

Seven years of clinical and laboratory research have provided us with a rather good knowledge of the infectious agent that causes hepatitis delta. This agent is a small RNA containing virus (hepatitis delta virus), which is functionally incomplete and needs the help of hepatitis B virus for infection and replication. It is unique also in respect to its RNA, which is smaller than the RNA of every other known RNA virus, but larger than the RNA of the viroids of higher plants. Animal experiments as well as clinical studies showed that hepatitis delta virus infection can be transmitted either simultaneously with hepatitis B, leading to a clinical picture which usually resembles that of hepatitis B alone, or as superinfection of a chronic HBsAg-carrier. The latter often leads to severe, and sometimes fatal, acute hepatitis, followed by chronic liver disease in as many as 30-40% of cases. The hepatitis delta virus is distributed world-wide, showing a high endemicity in Italy and some Arab countries, but also in certain risk groups such as intravenous drug addicts and haemophilics. Further epidemiological studies will probably reveal other foci where the hepatitis delta virus is endemic; especially in Africa, areas of high endemicity of hepatitis delta virus are suspected. Extensive research on delta agent is continuing: further clinical studies, using the highly sensitive method of DNA-RNA-hybridization for the detection of hepatitis delta virus RNA, will tell us more about the role of this virus in acute and chronic hepatitis, and future biochemical and biological research may be expected to increase our insight into the still enigmatic cooperation of the hepatitis delta virus and hepatitis B viruses.

Animals↗

Infectious hepatitis B virus from cloned DNA of known nucleotide sequence.

The infectivity of cloned hepatitis B viral DNA (HBV) has been tested in chimpanzees to identify a fully functional HBV genome and to assess the risk associated with its handling. Only one of two HBV DNA sequence variants tested was shown to be infectious. "Clone purified" virus of predicted nucleotide sequence was produced from the infectious HBV DNA, and the cloned viral genome was identical in structure with naturally occurring HBV. Infection could be initiated independent of whether circular monomeric or plasmid integrated dimeric forms of the viral genome were inoculated, but the infectivity of the DNA depended on liver cell transfection or intrahepatic injection. Intravenous injection of high doses of infectious HBV DNA did not induce hepatitis, suggesting that there is virtually no risk associated with routine laboratory handling of cloned HBV DNA.

Animals↗

[Viral hepatitis and immunoprophylaxis].

Today we distinguish 4 forms of viral hepatitis: hepatitis A, hepatitis B, hepatitis non-A, non-B and hepatitis occurring in the course of other viral diseases. The viruses of hepatitis A and hepatitis B have been identified but the agent(s) of hepatitis non-A, non-B remain unknown. Inoculation of normal pooled human immunoglobulin provides passive immunity for 2-3 months against hepatitis A but not against hepatitis B or hepatitis non-A, non-B. For passive protection against hepatitis B a special immunoglobulin with a high anti-HBs titer must be used whereas the protection against hepatitis non-A, non-B with immunoglobulin is uncertain. Live attenuated and noninfectious polypeptide vaccines for active immunisation against hepatitis A are currently developed and first clinical trials have begun with the live attenuated vaccine. A vaccine consisting of noninfectious highly purified HBsAg derived from the plasma of HBV carriers is in general use since two years and has proved safe and highly effective and vaccines are now developed from HBsAg obtained through molecular cloning of the HBsAg genome in plasmids and expression of the genome with HBsAg production in yeast cells. First clinical studies with this vaccine are encouraging and these as well as purely synthetic vaccines will in time replace the currently used vaccines. No vaccines could be developed so far against hepatitis non-A, non-B because the agent(s) of this disease are unknown.

Hepatitis A↗

Markers of hepatitis viruses A and B: direct comparison between whole serum and blood spotted on filter-paper.

The use of blood spotted on filter-paper is a cheap and convenient method for collecting, storing and transporting samples for analysis of markers of hepatitis virus B. Vaccine against viral hepatitis B is now available but is expensive, and, in order to make the best use of it, large-scale screening programmes need to be carried out in endemic areas prior to immunization campaigns. The sensitivity of the filter-paper method was compared with that of the analysis of whole serum, and the epidemiological data produced by the two methods were analysed. It was found that analysis of eluates of blood spotted on filter-paper cannot be recommended if accurate results are wanted, since large numbers of seropositive persons are likely to be missed; however, it may be a suitable method for detecting HBsAg-carriers and most anti-HBs-positive individuals prior to an immunization campaign.

Antigens, Viral↗

Vaccination against hepatitis B in patients with renal insufficiency.

To define the degree of renal insufficiency at which the immune response to vaccination against hepatitis B is impaired, anti-HB concentrations after vaccination with 20 micrograms HB-Vax at 0, 1 and 6 months were examined in 76 dialysis patients, 24 patients with incipient renal failure (S-creatinine 1.4-3.5mg/dl) and in 43 controls. Compared with controls, seroconversion rate and anti-HB concentrations were significantly (p less than 0.02) lower in patients with incipient renal failure. The time course of anti-HBs in dialysis patients with successful vaccination, either with three doses (0, 1, 6 months) or with five doses (0, 1, 2, 4, 6 months) of HB-Vax was compared with healthy controls. The proportion of patients losing anti-HBs and the decrease of antibody concentration was significantly greater in dialysis patients immunised with three doses of the vaccine. In dialysis patients vaccinated with five doses, the percentage losing HB antibodies was slightly higher than in controls, but final titres after 24 months were comparable.

Adult↗

Expansion of a minor subpopulation of peripheral blood lymphocytes (T8+/Leu 7+) in patients with haemophilia.

Immunological analysis of peripheral blood mononuclear cells (PBM) was performed in 20 patients with haemophilia A or B. One of the patients had never received clotting factor substitution in his life. Six different sources of lyophilized clotting factor were used for the other patients, but every given patient received factor from one source, exclusively. None of the patients exhibited lymphadenopathy and only one suffered from local bacterial infection. Mononuclear cell counts were within the normal range and mitogen stimulation with phythaemagglutinin (PHA) and concanavalin A (Con A) was found normal in all but two patients. Ratios of helper and suppressor cells (T4/T8) were below 1.0 in 10 of the patients. Some of these patients had a relative increase of T8+ cells and at the same time of Leu 7+ (natural killer (NK)/suppressor) cells. Double-marker analysis revealed that the subpopulation of cells expressing both the T8 and the Leu 7 antigen, which on the average accounted for 2.1% of the mononuclear cells in controls, was increased 4.5 fold (9.1%) in haemophilia patients. One patient exhibited 37.8% T8+/Leu 7+ double-marker cells. VEP13+ cells (active NK cells) were decreased below the normal range in 11 of the patients. Abnormal values for lymphocyte subsets were found in every treatment group. The patient who had never received any clotting factor exhibited normal values in all respects. In an additional set of patients, those with increased percentage of T8+/Leu 7+ cells exhibited decreased NK cell activity indicating that the T8+/Leu 7+ cells are not active NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Clinical evaluation of a recombinant hepatitis B vaccine.

Recombinant hepatitis B vaccine prepared from antigen expressed in yeast was given to 30 healthy young volunteers. Seroconversion rates and anti-HBs levels were compared with those in a control group matched for age and sex who had received plasma-derived hepatitis B vaccine. 4 weeks after the third immunisation results were similar in the two groups. In the recombinant vaccine group the immune response developed more slowly during the early phase and seroconversion rates and mean anti-HBs levels were slightly lower in males; this probably reflects use of a lower dose of recombinant vaccine (10 micrograms compared with 20 micrograms of the plasma vaccine). Side-effects were slight and antibody titres against Candida albicans were not increased in recipients of the recombinant vaccine.

Adult↗

[Antibodies against human T-cell leukemia virus type III in acquired immunodeficiency syndrome and persistent lymphadenopathy].

HTLV III and LAV, retroviruses which have recently been described in the United States and France and which seem to be different isolates of the same virus, are closely associated with the acquired immune deficiency syndrome (AIDS) and the lymphadenopathy syndrome (LAS). Sera from male homosexuals from the Federal Republic of Germany with AIDS or LAS were examined for antibodies to HTLV III (anti-HTLV III) by means of the enzyme linked immunoadsorbent assay (ELISA) and by an indirect immunofluorescence assay. 53% of the patients were anti-HTLV III positive as were 20% of symptomless homosexual men.

Acquired Immunodeficiency Syndrome↗