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Biomedical subjects

J Löwer

Publications and source records attributed to J Löwer.

At least 55 records · Page 3Linked to original sources
PubMed1991

Epidemiology and pathogenicity of human retroviruses.

The human retroviruses can be divided into oncovirus (HTLV-I and HTLV-II) and lentivirus strains (HIV-1 and -2). The HTLVs are endemic in Central Africa, the Caribbean Islands and in southwest Japan, but now tend to spread through the i.v.-drug user population in the USA and in some countries in Western Europe. HTLV infection is associated with a malignant form of adult T-cell leukemia, tropical spastic paraparesis (TSP) and an associated myelopathy (HAM). The pathogenic mechanisms of HTLV are as yet poorly understood. HIV infection is spreading rapidly almost world-wide and has reached epidemic proportions in Central Africa, parts of South America and in certain populations in industrialized countries that have risk behaviour for contracting venereal or blood-borne infections. The mechanisms of HIV-induced immune suppression are still not entirely clear, as direct T-lymphocyte destruction after viral infection cannot account for the almost complete loss of CD4 T-cells in the final stages of disease. Various indirect mechanisms of HIV-induced immune cell destruction are outlined below.

Biological Products↗
PubMed1991

[Risks of a cartilage-bone bank with reference to HIV infection].

Allogenic transplants have an established place in reconstructive procedures. For years it has been suspected that lyophilized dura mater can transmit Creutzfeld-Jakob disease. HIV infection with fully manifest AIDS and a mortality of up to 100% is now also increasing in significance. It is necessary to assess the risk of transferring HIV with allogenic transplants because HIV passes into the cell via specific surface receptors and is integrated within the chromosome. Experimental data on disinfection and sterilization of allogenic transplants stored within chromosomes and their inactivation are not available. Allogenic transplants are only used in operations for life-threatening disease. As a rule, these are elective operations which must meet the highest safety standards, also with regard to the danger of infection. Collaboration with a transplantation team is essential.

Bone Transplantation↗
PubMed1990

Risk of tumor induction in vivo by residual cellular DNA: quantitative considerations.

Certain genes, termed oncogenes, have the ability to transmit the transformed phenotype from tumor cells to hitherto normal cells in vitro and in vivo. This observation is the basis for the concern that medicinal products derived from tumor cell lines could contain possibly tumorigenic contaminating cellular DNA. A comparison between the number of oncogenes necessary for the induction of tumors in a suitable animal model and the quantity in 100 pg residual cellular DNA was carried out. It is shown that the latter contains less than a billionth of the number needed to induce tumors in half of the animals tested. Some factors implicit to this calculation such as the validity of the model system, the linearity of the dose response curve, the concept of multistep carcinogenesis, the amplification of oncogenes, and the transfection enhancing effect of other constituents of the drug are discussed. In summary, 100 pg residual cellular DNA per dose seems to be a safe and, therefore, an acceptable upper limit provided that some factors such as excessive amplification of oncogenes, co-purification of oncogenic DNA with the product or some transfection mediating activity can be excluded.

Animals↗
PubMed1989

HIV and HIV-infected cells differentially activate the human complement system independent of antibody.

The human retroviruses HTLV-I and HIV-I have previously been shown not to be lysed by human serum. An interaction between HIV and the complement system, however, has not been investigated in any detail. In this report we show that purified HIV as well as HIV-infected cells activate the complement system. In the case of virus-infected cells this activation is mediated by the alternative pathway of complement, whereas the classical pathway seems to be in operation for the triggering of the complement system by purified virus and recombinant envelope glycoprotein (gp 160). We demonstrate that this leads to the deposition of C3b and/or C3bi on the surface of infected cells. But the HIV-infected cells are not lysed by human complement. C3 fragments deposited on the surface of HIV-infected cells are capable of mediating immune adherence to complement receptor-bearing cells, such as human erythrocytes and phagocytes. Whether this might have an influence on infectivity of HIV for certain cells bearing complement receptors has yet to be shown.

Cell Line↗
PubMed1989

Azidothymidine triphosphate is an inhibitor of both human immunodeficiency virus type 1 reverse transcriptase and DNA polymerase gamma.

The reverse transcriptase from human immunodeficiency virus type 1 was purified from the virus to near homogeneity. The enzyme was shown to possess both RNA-dependent and DNA-dependent DNA-synthesizing activity. Activated DNA as a heteropolymeric substrate was used as efficiently as was the homopolymeric substrate poly(rA)-oligo(dT). The Michaelis-Menten constants were determined for each of the four nucleotides needed to elongate a natural template primer. Azidothymidine triphosphate, a well-known inhibitor of the enzyme, inhibited the enzyme competitively with respect to dTTP and noncompetitively with respect to the other nucleotides. Azidothymidine triphosphate acted as an efficient inhibitor of cellular DNA polymerase gamma, whereas other enzymes of eucaryotic DNA metabolism, namely, DNA polymerase alpha-primase and DNA polymerase beta, were not inhibited. This finding may explain why some acquired immunodeficiency syndrome patients suffer side effects during azidothymidine therapy.

DNA Polymerase III↗
PubMed1988

Inhibition of HIV-1 RNA-dependent DNA polymerase and cellular DNA polymerases alpha, beta and gamma by phosphonoformic acid and other drugs.

Potential specific inhibitors of HIV RNA-dependent DNA polymerase (RDDP) were examined in an in-vitro test system containing purified HIV-1 RDDP, or functionally purified cellular DNA-dependent DNA polymerases alpha, beta and gamma. A wide variety of drugs were tested for their specific inhibitory activity against the viral enzyme to identify substances which, at the same concentration, did not inhibit the cellular DNA polymerases. Phosphonoformic acid and derivatives were found to be the most specific inhibitors, followed by chlortetracycline.

Antiviral Agents↗
PubMed1988

Reverse transcriptases from human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIVMAC) are susceptible to inhibition by foscarnet and 3'-azido-3'-deoxythymidine triphosphate.

Reverse transcriptases from human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIV) were investigated with respect to susceptibilities to the reverse transcriptase inhibitors foscarnet and 3'-azido-3'-deoxythymidine triphosphate (AZTTP). The different reverse transcriptases had the same sensitivity to foscarnet (50% inhibition at 0.10 to 0.16 microM). The Ki values for AZTTP were 0.01 to 0.02 microM for HIV-1 reverse transcriptase and 0.02 to 0.03 microM for HIV-2 and SIVMAC reverse transcriptases.

Animals↗
PubMed1988

[Gene technology in the diagnosis of viruses and vaccine development].

The development of genetechnological methods since the beginning of the 1970's allowed the molecular cloning of partial or complete viral genomes and the sequencing of their nucleic acids. On this basis, new tools for viral diagnostics are available: molecular probes for hybridization techniques and synthetic peptides or highly purified proteins for the specific detection of antibodies. While the role of synthetic peptides as vaccines seems to be limited, complete viral surface proteins produced by gene technological methods are already used for vaccination in man. The advantages and disadvantages of production in bacteria, in yeast and in higher eukaryotic cells of polypeptides designed as subunit vaccines are discussed. An additional, attractive model is the synthesis of antigens immediately in the host, directed by a recombinant vaccinia virus. Another promising approach is the establishment of potent and safe live vaccines by the introduction of defined mutations or deletions into a viral genome, based on the previous elucidation of the molecular mechanism of attenuation.

Cloning, Molecular↗
PubMed1987

Genome analysis and reverse transcriptase activity of human teratocarcinoma-derived retroviruses.

Five of five human teratocarcinomas cultured in vitro could be induced to synthesize retrovirus-like particles, albeit in extremely low amounts. The accumulation and purification of the human teratocarcinoma-derived retrovirus (HTDV) from one of these cell lines allowed characterization of its genomic material as high mol. wt. (60S) RNA. Partial purification of HTDV-associated RNA-dependent DNA polymerase (reverse transcriptase) has also been achieved. HTDVs are easily distinguishable from the exogenous human T-lymphotropic viruses and human immunodeficiency viruses by morphological, biological and immunological criteria.

Humans↗
PubMed1987

[Retroviruses and the development of lymphoma].

Retroviruses are small, RNA-containing enveloped viruses which are widely distributed in nature. They exist in many animal species as well as in man. Exogenous virus strains are horizontally transmitted between individuals of a given species, like all other virus groups. Endogenous virus strains have managed some time during evolution to infect germ line cells like oocytes and spermatocytes and are thus transmitted vertically from parents to offspring. Several retrovirus strains possess oncogenes, i.e., acutely tumor-inducing genes. There are four human retrovirus strains so far. The initially discovered strain, HTLV-I, is accepted to be a co-factor in the development of an acute T-cell leukemia in adults. HTLV-II has repeatedly been isolated from cells of patients with hairy cell leukemia. Its etiological significance is unclear at present. HTLV-III/LAV-1, now designated HIV-1, is the causative agent of AIDS. HTLV-IV and LAV-2 are additional HIV-1 related strains and are supposed to cause AIDS as well. What is known about the pathogenicity of the human retrovirus strains will be discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Detection of antibodies to HTLV-III in commercially available immunoglobulin preparations.

Samples of 96 polyvalent and virus-specific immunoglobulin batches commercially available in West-Germany were tested by enzyme-linked immunoassay and immunoblot for the presence of anti-HTLV-III antibodies. 37% of the polyvalent and 87% of the virus-specific batches were positive. It was concluded that these preparations are still safe and because of their reportedly low titer neutralizing antibodies possibly beneficial in certain cases, such as newborns of HTLV-III positive mothers or after accidental exposure to infectious material in clinics or laboratories.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Functional purification and enzymic characterization of the RNA-dependent DNA polymerase of human immunodeficiency virus.

The RNA-dependent DNA polymerase (RDDP) of human immunodeficiency virus (HIV) was purified from sucrose density gradient-banded virus by four successive procedures: anion exchange chromatography, cation exchange chromatography, affinity chromatography on oligo(dT)-cellulose and adsorption chromatography on hydroxyapatite. The enzyme preparation was free of cellular DNA-dependent DNA polymerase activity. The properties of HIV RDDP were determined with a variety of template-primers. Generally, the enzyme used Mg2+ for optimal activity except with (Cm)n X (dG)12-18 as template-primer. Kinetic data (Michaelis constant, Hill coefficient) were calculated for several substrates.

Chromatography↗
PubMed1984

Human teratocarcinomas cultured in vitro produce unique retrovirus-like viruses.

We have previously reported that among a series of human tumours investigated, only human teratocarcinoma cell lines derived from testicular tumours or pulmonary metastases of patients in Germany and the U.S.A. produced retrovirus-like particles spontaneously, albeit in low amounts. In a recent publication electron microscopical data suggested that the human teratocarcinoma-derived ( HTD ) particles were morphologically closely related, but not identical, to the type C retroviruses of animals. In this communication, the explantation of three human teratocarcinoma cell lines is briefly described. Evidence is presented that HTD particles (i) are synthesized only in a fraction of the epithelioid and differentiating cells; (ii) can be induced biochemically in a manner characteristic of retroviruses; (iii) either are not infectious or possess a peculiar host range; (iv) are immunologically unrelated to animal retrovirus strains; (v) possess an endogenous RNA-dependent DNA polymerase activity that can be banded at 1.16 g/ml in linear sucrose gradients. These results may be taken as suggestive evidence that HTD particles represent a novel group of unique retroviruses.

Antigens, Viral↗