Search PubMed⌕ Search

Biomedical subjects

B Flehmig

Publications and source records attributed to B Flehmig.

At least 19 recordsLinked to original sources
PubMed1992

Myelopoiesis in vitro is suppressed by hepatitis A virus.

Perturbations of hematopoietic regulation ranging from transient granulocytopenia to rare cases of bone marrow failure are associated with infections due to hepatitis A virus (HAV). In an attempt to elucidate the pathogenetic mechanisms we had previously established that HAV has a direct suppressive effect on human bone marrow progenitors (CFU-GM, -GEMM, BFU-E). These studies were extended to long-term bone marrow cultures (LTBMC): Inoculation of bone marrow mononuclear cells with HAV did not interfere with the establishment of an adherent stromal layer, nor did the inoculation of already established layers cause any morphologically recognizable changes to the stroma. In contrast, a significant and progressive decline of the CFU-GM content in the culture supernatants was demonstrated. HAV antigen was detected by APAAP stain in a subpopulation of stromal cells, and sequential estimations of virus titers in the supernatants provided evidence for viral replication in primary bone marrow cultures. Interferon-gamma and tumor necrosis factor-alpha levels of infected cultures did not differ from those of uninfected controls. These findings argue for a direct suppression of (pre-) CFU-GM by HAV in a model system (LTBMC) lacking an immune defense which would limit viral replication.

Antigens, Viral↗
PubMed1992

Antitumor activity of the pineal gland: effect of unidentified substances versus the effect of melatonin.

There is growing evidence that the pineal gland has antineoplastic properties which, however, can only partially be attributed to its hormone melatonin. While the in vivo tumor-inhibiting activity of melatonin is established, observations on its in vitro effects have been contradictory. The effect of this substance was investigated on six human cancer cell lines and compared to the activity of a partially purified, melatonin-free low molecular weight pineal extract (UMO5R). Melatonin showed hardly any effect but UMO5R was capable of inhibiting the growth of all the six cell lines tested. It is therefore concluded that a direct inhibiting action on tumor cells is not a general physiological role of melatonin as opposed to UMO5R. It will be worthwhile to purify the yet unidentified pineal antitumor activity since it may have a considerable therapeutic potential.

Humans↗
PubMed1990

Hepatitis A.

Known properties of hepatitis A virus are described in this article. HAV is a small non-enveloped picornavirus, grouped in the Enterovirus family, with unique biological features. The genome structure resembles that of other picornaviruses. Replication in cell cultures takes much longer than that of other picornaviruses and the yield is much lower. HAV is extremely heat- and pH-stable. Variants may induce cytopathogenic effects in vitro. Normally, however, the virus is non-cytopathogenic. The elimination of virus in vivo is assumed to be caused by action of HAV antigen specific CD8+ lymphocytes. In industrialized countries there is a declining incidence of reported hepatitis A cases, and the prevalence of antibodies in younger populations is low. Vaccines have been developed and in studies using human volunteers, good immunogenicity has been demonstrated. In the very near future a cell cultured derived, highly purified, inactivated vaccine will be available.

Animals↗
PubMed1990

Simultaneous vaccination for hepatitis A and B.

Seronegative volunteers (15) were vaccinated at three 1-month intervals with a combined hepatitis A and B vaccine. The vaccine contained a killed hepatitis A vaccine made from hepatitis A virus (HAV) propagated in diploid human fibroblast cell cultures and hepatitis B surface antigen (HBsAg) produced in yeast. After only one injection, all volunteers developed neutralizing antibodies for HAV with antibody titers comparable to those found after gamma globulin administration. Compared with the antibody titers in sera of volunteers vaccinated with HAV vaccine alone, the antibody titers against HAV were significantly higher in the sera of the volunteers simultaneously vaccinated against hepatitis B virus (HBV) after three vaccinations. Of 15 volunteers, 14 seroconverted against HBV after three injections. In 11 volunteers tested 48 weeks after vaccination, antibody titers against HAV and HBV remained high.

Adult↗
PubMed1989

Immunogenicity of a killed hepatitis A vaccine in seronegative volunteers.

32 volunteers who lacked antibody to hepatitis A virus (HAV) received, at intervals of one month, three injections of a killed vaccine made from HAV propagated in diploid human fibroblast cell cultures. In 16 the vaccine was coupled with aluminium hydroxide as adjuvant. The serconversion rates measured by radioimmunoassay, with and without adjuvant respectively, were 13% and 25% at four weeks, 81% and 89% at eight weeks, and 94% and 100% at twelve weeks. Four weeks after the third injection all volunteers had high neutralising antibody titres. Twelve weeks later the titres of anti-HAV and anti-HAV neutralising antibodies had not declined.

Adult↗
PubMed1989

Liver-derived cytotoxic T cells in hepatitis A virus infection.

An autologous in vitro model was developed to analyze the immunologic cause of liver tissue injury during hepatitis A virus (HAV) infection. Human T lymphocytes infiltrating the livers of two patients with acute HAV infection were isolated from liver biopsy cores, cloned, and expanded in vitro. Procedures using a cell culture system with HAV-infected autologous skin fibroblasts demonstrated that 42% and 53% of the liver-infiltrating CD8+ clones were HAV-specific and that they kill HAV-infected skin fibroblasts in a human leukocyte antigen-restricted manner. Data show virus-specific killing by liver-infiltrating T lymphocytes in man and support the hypothesis that liver cell injury in acute HAV infection is mediated by HAV-specific CD8+ T lymphocytes and is not caused by a cytopathic effect of the virus itself.

Adult↗
PubMed1989

Acid stability of hepatitis A virus.

The acid stability of unpurified and highly purified hepatitis A virus (HAV) was tested and compared with that of poliovirus type 1, coxsackievirus types A9 and B1 and echovirus type 9. Only HAV had a high residual infectivity after 2 h of exposure to pH 1 at room temperature, remaining infectious for up to 5 h. At 38 degrees C, pH 1, HAV remained infectious for 90 min. Highly purified HAV was found to be infectious for 8 h at pH 1 and room temperature. This indicates that the increased stability is not due to protection by cellular material attached to the virus, but is a virus-specific marker. Under the same conditions, at pH 1 and room temperature, unpurified and highly purified HAV antigens were traceable for 5 and 4 h respectively.

Cell Line↗
PubMed1989

Partial purification of a polypeptide extract derived from ovine pineal that suppresses the growth of human melanoma cells in vitro.

A combination of gelfiltration and reverse-phase high performance liquid chromatography with postcolumn antitumour assay has been developed. A melatonin insensitive human melanoma cell strain was used to guide the purification of the antitumour effect of an ovine pineal aqueous extract (MW 1,000 to 10,000) that possessed the ability to decrease the hypophysiotropic activity of rat and mice hypothalami in vitro. This allows a specific identification of a pineal factor (MW 2,000 to 6,000) that inhibits the growth of human melanoma cells at a dose of 0.47 mg/ml medium. It was shown that the activity of this pineal compound differs from structures known to be present in the pineal, such as melatonin, pteridines, and beta-carbolines. There appears to be evidence for a peptidic nature of this pineal antitumour factor.

Animals↗
PubMed1989

Comparison of ozone inactivation, in flowing water, of hepatitis A virus, poliovirus 1, and indicator organisms.

In steadily flowing water at 20 degrees C and pH 7, five organisms had the following order of resistance to ozone (at constant levels of ozone): poliovirus 1 (PV1) less than Escherichia coli less than hepatitis A virus (HAV) less than Legionella pneumophila serogroup 6 less than Bacillus subtilis spores. The tests were repeated at 10 degrees C with HAV, PV1, and E. coli. Ozone inactivation of HAV and E. coli was faster at 10 degrees C than at 20 degrees C. At 20 degrees C, 0.25 to 0.38 mg of O3 per liter was required for complete inactivation of HAV but only 0.13 mg of O3 per liter was required for complete inactivation of PV1.

Bacillus subtilis↗
PubMed1988

Partial purification of (a) low molecular weight ovine pineal compound(s) with an inhibiting effect on the growth of human melanoma cells in vitro.

An in vitro human melanoma cell assay was used to work up the partial purification of (a) low molecular weight (MW) substance(s) from aqueous extracts of ovine pineal tissue shown to contain a growth-inhibiting activity. A combination of paper chromatography, ion-exchange and reverse-phase high performance liquid chromatography with post-column antitumor assay has been developed. This allows a specific identification of an ovine pineal factor (MW less than 500) which inhibits the growth of human melanoma cells in vitro. The substance was partially purified to about 1,000 times as compared to the IC100-value of the starting material (retentate 5). The growth inhibition of human melanoma cells in culture was complete at a dose of 0.1 microgram/ml of purified pineal factor(s). It was demonstrated that the activity of this pineal compound differs from some substances known to be present in the pineal, such as melatonin, serotonin, peridines and beta-carbolines. The activity was not destroyed by treatment with proteolytic enzymes.

Animals↗
PubMed1988

Human gamma interferon production by cytotoxic T lymphocytes sensitized during hepatitis A virus infection.

The production of interferon (IFN) during a chromium-51 release assay with hepatitis A virus (HAV)-infected fibroblasts and autologous peripheral blood lymphocytes from patients with acute HAV infection was studied to determine whether IFN plays a role in immunopathogenesis of hepatitis A infection in humans. Skin fibroblasts of eight patients after acute HAV infection and from two control persons without history of current or past HAV infection were infected with HAV. Peripheral blood lymphocytes were collected at different times after the onset of icterus and tested in a chromium-51 release assay against autologous HAV-infected skin fibroblasts for their cytolytic and IFN-producing activity. The IFN produced during the assay was characterized and found to have the properties of human gamma IFN. Cytotoxicity and gamma IFN release were virus specific. The cell types responsible for both functions were characterized and found to be in the HLA-dependent T8+ lymphocyte subset. Considering that gamma IFN has an antiviral effect on persistent HAV infection in vitro and that it probably accounts for stimulation of HLA class I antigen expression on hepatocytes, our experimental results presented here demonstrate that human gamma IFN produced by HAV-specific T cells may participate in pathogenesis of hepatitis A infection in humans.

Cells, Cultured↗
PubMed1988

[Vaccines against hepatitis viruses].

A short characterization of hepatitis A virus and hepatitis B virus is given. The development of hepatitis B vaccines is described, including the presently available vaccines. Experimentally developed vaccines and possible vaccine developments against hepatitis B virus are discussed. The current status of the development in the field of hepatitis A virus vaccines is presented. Results of hepatitis A live vaccines as well as results of hepatitis A killed vaccine developments are reported.

Hepatitis B Surface Antigens↗
PubMed1987

Immunogenicity of a hepatitis A virus vaccine.

Hepatitis A virus (HAV) strain HAV/HFS/GBM was adapted to and grown in human diploid fibroblast cells. The HAV was concentrated by ammonium sulphate precipitation and high-speed centrifugation. The virus was inactivated by beta-propiolacton and purified by sedimentation through a 20% solution of sucrose and by CsCl gradient centrifugation. The immunogenicity of different preparations was tested in mice, guinea pigs, and goats. The immune response after vaccination was tested by determination of anti-HAV with RIA and of neutralizing antibodies with an appropriate test system. Results showed that anti-HAV titers of 1:1,000 and greater, as well as neutralizing antibody titers of 1:1,000 and greater, were found in sera of animals vaccinated with different preparations. It became evident that good anti-HAV titers persisted over a period of at least 1.5 years in goats and mice after immunization with a semipurified HAV vaccine, and titers up to 1:200 were present in mice 2 years after vaccination with a highly purified HAV vaccine.

Animals↗