Biomedical subjects

M S Reitz

Publications and source records attributed to M S Reitz.

147 records · Page 9Linked to original sources

PubMedDate not supplied

Transformation of NIH 3T3 cells by a human c-sis cDNA clone.

The mechanism of leukaemogenic transformation by human T-cell leukaemia/lymphoma virus (HTLV), a retrovirus implicated in the aetiology of certain adult T-cell leukaemias and lymphomas, is unknown but is conceivably associated with the expression of the cellular analogues of retroviral oncogenes. The HUT-102 cell line, derived from a cutaneous T-cell lymphoma and infected with HTLV, expresses several cellular oncogenes. It is unusual among haemopoietic cell lines in that one of these is c-sis, the gene from which the oncogene v-sis of the simian sarcoma virus was derived, and perhaps the gene for platelet-derived growth factor (PDGF). To explore the possible role of c-sis expression in HTLV-induced disease, we have obtained cDNA clones of c-sis from HUT-102 cells. Here we describe two such clones and report that one of them transforms NIH-3T3 cells. This is the first example of transformation of NIH-3T3 cells by a human onc gene other than c-ras or Blym, as well as the first demonstration of transformation by a human cDNA clone.

Animals↗

PubMedDate not supplied

Sequence of simian immunodeficiency virus and its relationship to the human immunodeficiency viruses.

The characterization of HIV-1 (HTLV-III/LAV), the human retrovirus associated with AIDS (acquired immune deficiency syndrome) has led to the identification of a group of related human and simian retroviruses which also infect CD4-bearing T lymphocytes. Simian T-lymphotropic virus type III (simian immodeficiency virus) from macaques (STLV-IIIMAC) induces symptoms similar to those of AIDS in infected macaques, but isolates from African green monkeys (STLV-IIIAGM) and mangabeys (STLV-IIMM) appear to be non-pathogenic in these animals. A human virus immunologically related to STLV-IIIAGM (HTLV-IV), reported to have been isolated from healthy humans, has been shown to be almost identical to STLV-IIIAGM, which has called into question the independent origin of these viruses. Here we report the complete DNA sequence of STLV-IIIAGM and analyse its relationship with the genomes of the HTLV-IIIB strain of HIV-1, HIV-2ROD (previously called LAV-2) and several ungulate lentiretroviruses. STLV-IIIAGM and HIV-2 are closely related, and more distantly related to HIV-1.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

HIV-1 protease inhibitor ritonavir modulates susceptibility to apoptosis of uninfected T cells.

OBJECTIVE: Clinical experience with HIV-1 protease inhibitors (PIs) in the treatment of AIDS frequently has shown that increases in CD4+ T-cell counts can be independent of HIV-1 inhibition by these drugs. This disconnection between viral load and CD4 counts led us to investigate how the PI ritonavir directly affects leukocyte activation in vitro, using peripheral blood mononuclear cell (PBMC) fractions derived from normal donors. METHODS AND RESULTS: When uninfected PBMC cultures were treated for 72 hours with ritonavir at concentrations similar to or lower than that shown to be effective in vivo, an increase in cell viability was observed. The susceptibility of PBMCs to apoptosis was markedly decreased after ritonavir treatment and correlated with lower levels of caspase-1 expression, decreases in annexin V staining, and reduced caspase-3 activity. Induction in vitro of tumor necrosis factor (TNF) production by PBMCs and monocytes was inhibited by ritonavir in a time- and dose-dependent manner at nontoxic concentrations. CONCLUSION: Based on our data, we conclude that the HIV-1 PI ritonavir is an immune modulator that may affect leukocyte activation and apoptosis as an important part of its therapeutic benefit.

Annexin A5↗