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Biomedical subjects

H Varmus

Publications and source records attributed to H Varmus.

At least 37 records · Page 2Linked to original sources
PubMed1994

Basic science and the NIH.

The following is an edited version of the Keynote Speech delivered at the Annual Meeting of the American Society for Cell Biology by Harold Varmus, Director of the National Institutes of Health. The address, entitled Basic Science and the NIH, was given at the opening of the meeting in New Orleans on December 11, 1993. It was Varmus' first public policy talk as NIH Director.

National Institutes of Health (U.S.)↗
PubMed1989

Transgenic mice and host cell mutants resistant to transformation as model systems for identifying multiple components in oncogenesis.

Tumorigenesis appears to be a multistep process involving mutations of conventional, dominantly acting proto-oncogenes, mutations of other genes that may act in a recessive manner, and interactions (or a lack of interactions) between the products of mutant and wild-type genes. Our laboratory is using a few well-established, dominant oncogenes to pose experimental questions that could lead to a better understanding of the more elusive genetic interactions which occur during tumour development. Two such situations are described: (1) We have created a line of transgenic mice that carry the int-1 proto-oncogene under the control of the enhancer element in the mouse mammary tumour virus long terminal repeat. Such mice express the transgene in mammary glands, salivary glands and male reproductive tract; mammary glands from both male and female animals are grossly hyperplastic, yet tumours arise rarely in the males and sporadically in the females (80% of female mice have one or a few tumours by six months of age). Thus expression of int-1 in these mice appears to place a large number of mammary cells at risk for secondary events that lead to carcinogenesis, providing a provocative experimental context for identifying such secondary events. (2) We have isolated a rat cell line that lacks most of the characteristics of transformed cells, despite the expression of two wild-type copies of the v-src gene of Rous sarcoma virus. This line harbours what appears to be a dominant mutation in an unidentified gene that renders the cell resistant to transformation by v-src and several other oncogenes. Isolation of the mutant gene responsible for suppressing transformation in this line should provide new insights into the interactions between oncoproteins and other cellular proteins.

Animals↗
PubMed1989

Detection of antibodies against hepatitis B virus polymerase antigen in hepatitis B virus-infected patients.

By the use of a truncated recombinant hepatitis B virus polymerase antigen, we have characterized a series of patient sera for anti-hepatitis B virus polymerase antibodies. Seven of 54 (13%) had antipolymerase antibodies detectable by Western blot analysis, and no close correlation was apparent between the disease status and patient's immune response against hepatitis B virus polymerase antigen. Our results indicate that serologic responses to the viral polymerase are demonstrable but suggest that such antibodies are not likely to be clinically useful as diagnostic or prognostic markers of infection.

Blotting, Western↗
PubMed1989

Identification of genes from pattern formation, tyrosine kinase, and potassium channel families by DNA amplification.

The study of gene family members has been aided by the isolation of related genes on the basis of DNA homology. We have adapted the polymerase chain reaction to screen animal genomes very rapidly and reliably for likely gene family members. Using conserved amino acid sequences to design degenerate oligonucleotide primers, we have shown that the genome of the nematode Caenorhabditis elegans contains sequences homologous to many Drosophila genes involved in pattern formation, including the segment polarity gene wingless (vertebrate int-1), and homeobox sequences characteristic of the Antennapedia, engrailed, and paired families. In addition, we have used this method to show that C. elegans contains at least five different sequences homologous to genes in the tyrosine kinase family. Lastly, we have isolated six potassium channel sequences from humans, a result that validates the utility of the method with large genomes and suggests that human potassium channel gene diversity may be extensive.

Amino Acid Sequence↗
PubMed1989

Function, location, and regulation of the src protein-tyrosine kinase.

The physiological roles, precise locations, and relevant targets of the 60 kD protein-tyrosine kinase encoded by viral and cellular src genes p60src are not known, despite intensive study. We describe recent work that bears upon these unresolved problems: (i) p60c-src is phosphorylated during mitosis on threonine and serine residues by the protein kinase encoded by the mammalian homologue of cdc2, suggesting that c-src may contribute to the phenotype of mitotic cells; (ii) multiple regions in the amino-terminal portion of p60src are required for its proper intracellular localization--a short signal for myristylation and signals for association with cytoplasmic granules and with perinuclear and plasma membranes; and (iii) regions (called SH3 and SH2) upstream of the kinase domain modulate the behavior of p60src in complex ways, with some mutations in SH2 rendering p60 host-dependent for transformation. The latter mutants may prove to be powerful tools for identifying proteins that modify or serve as targets for src-encoded protein-tyrosine kinases.

Amino Acid Sequence↗
PubMed1988

Retroviruses.

First brought to scientific attention as infectious cancer-causing agents nearly 80 years ago, retroviruses are popular in contemporary biology for many reasons. (i) The virus life cycle includes several events--in particular, reverse transcription of the viral RNA genome into DNA, orderly integration of viral DNA into host chromosomes, and utilization of host mechanisms for gene expression in response to viral signals--which are broadly informative about eukaryotic cells and viruses. (ii) Retroviral oncogenesis usually depends on transduction or insertional activation of cellular genes, and isolation of those genes has provided the scientific community with many of the molecular components now implicated in the control of normal growth and in human cancer. (iii) Retroviruses include many important veterinary pathogens and two recently discovered human pathogens, the causative agents of the acquired immunodeficiency syndrome (AIDS) and adult T cell leukemia/lymphoma. (iv) Retroviruses are genetic vectors in nature and can be modified to serve as genetic vectors for both experimental and therapeutic purposes. (v) Insertion of retroviral DNA into host chromosomes can be used to mark cell lineages and to make developmental mutants. Progress in these and other areas of retrovirus-related biology has been enormous during the past two decades, but many practical and theoretical problems remain to be solved.

Animals↗