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Biomedical subjects

L Ratner

Publications and source records attributed to L Ratner.

177 records · Page 10Linked to original sources
PubMed1980

Chemotherapy of recurrent ovarian carcinoma with cis-dichlorodiammine platinum II and adriamycin.

Forty-six patients with recurrent disseminated ovarian carcinoma were treated with a combination of cis-dichlorodiammine platinum II (DDP) 50 mg/m2 and adriamycin 50 mg/m2 given intravenously every 3 weeks. All patients had failed prior chemotherapy. The combination of adriamycin and DDP produced objective responses in 14 of 46 patients. Severe side effects were frequent, but no patient died as a result of treatment. Disease in 4 of 7 complete responders is currently in remission up to 4 years.

Adult↗
PubMed1978

Interferon-associated, dsRNA-dependent enzyme activities in a mutant 3T6 cell engaged in the semiconstitutive synthesis of interferon.

Cytoplasmic extracts of untreated cultures of a virus-resistant mutant of mouse 3T6 cells, designated 3T6-VrB2, contain two double-stranded, RNA-activated enzyme activities associated with interferon action. These are the synthesis of a low molecular weight oligonucleotide inhibitor of cell-free protein synthesis from ATP, and the phosphorylation of a 67,000 dalton polypeptide by transfer of the gamma phosphate of ATP. Basal levels of both enzyme activities are detectable in extracts of untreated parental 3T6 cells, and are greatly enhanced upon interferon pretreatment. A procedure was developed, using a nonionic detergent to effect cell lysis, which allowed the analysis of the protein kinase activity from as few as 2 x 10(7) cells. Using this procedure, direct proportionalities were demonstrated between the concentration of interferon to which 3T6 cells were exposed, and both the level of protein kinase activity and the magnitude of the antiviral state were established in these cells. Furthermore, untreated cultures of 3T6-VrB2 exhibited both an antiviral state and an intracellular protein kinase activity equal to that of cultures of the parental 3T6 cells pretreated with a single concentration of mouse interferon.

Cell Line↗
PubMed1978

Interferon action: two distinct pathways for inhibition of protein synthesis by double-stranded RNA.

Double-stranded RNA inhibits protein synthesis in at least two ways. It activates a protein kinase that blocks peptide chain initiation by phosphorylating the peptide chain initiation factor eIF-2 and also activates an endonuclease that inactivates different mRNAs at different rates. The protein kinase and the endonuclease have been partially purified from interferon-treated Ehrlich ascites tumor cells. The 2',5'-oligoadenylates [pppA(2'p5'A)n], found found earlier to be mediators in the activation of the endonuclease by double-stranded RNA, are not mediators in the activation of the protein kinase by double-stranded RNA.

Adenine Nucleotides↗
PubMed1977

Messenger RNA methylation, translation and degradation in extracts of interferon-treated cells.

Extracts from interferon-treated, not virus infected EAT cells differ in several biochemical characteristics from extracts of untreated cells. Some of these differences are manifested only if the extracts are supplemented with ds RNA and ATP. Thus, in the extracts from interferon-treated cells these supplements activate a protein kinase and an endonuclease activity as well as an inhibitor of the translation of messenger RNA. The effect of the same supplements in extracts of untreated cells is much less pronounced. Other differences between the two types of extracts do not seem to depend on the addition of ds RNA and ATP. These include an impairment of mRNA cap methylation and an inhibition of peptide chain elongation that can be overcome by the addition of tRNA. The treatment of human (HeLa S3) cells with human interferon is manifested in the cell extract similarly to the treatment of EAT cells with mouse interferon. Studies are underway to isolate and characterize the ds RNA activated enzymes and the inhibitors and to establish how the presence of these in extracts from interferon-treated cells can account for the impairment of virus replication by interferon.

Adenosine Triphosphate↗
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

Complete nucleotide sequence of the AIDS virus, HTLV-III.

The complete nucleotide sequence of two human T-cell leukaemia type III (HTLV-III) proviral DNAs each have four long open reading frames, the first two corresponding to the gag and pol genes. The fourth open reading frame encodes two functional polypeptides, a large precursor of the major envelope glycoprotein and a smaller protein derived from the 3'-terminus long open reading frame analogous to the long open reading frame (lor) product of HTLV-I and -II.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

A molecular clone of HTLV-III with biological activity.

Acquired immune deficiency syndrome (AIDS) is an epidemic immunosuppressive disease characteristically associated with a depletion of T lymphocytes of the helper/inducer phenotype. Numerous converging lines of research have implicated a human T-cell lymphotropic retrovirus, HTLV-III, in the pathogenesis of AIDS. Recently, several distinct forms of the HTLV-III genome were molecularly cloned in phage and extensively characterized. In the present study, a clone containing full-length HTLV-III proviral DNA was inserted into a plasmid and used to transfect cord blood T cells from normal newborn humans. We demonstrate that this molecular clone is infectious in vitro and causes marked cytopathic effects on T-cell cultures. This is the first direct evidence that the HTLV-III genome, rather than a minor component of the virus complex, is cytopathic for T cells. Using this biologically competent clone and mutants derived from it, it should now be possible to localize the subgenomic regions that contribute to the biological effects of HTLV-III.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Prevention of stress-induced erosive gastritis by parenteral administration of arachidonic acid.

Stress-induced mucosal ulcerations are associated with a decreased synthesis of mucosal prostaglandin (PG) E2. This phenomenon is poorly understood. To investigate whether it is due to a decreased availability of the necessary substrates to the mucosa, four groups of 10 Holtzman rats were studied: group 1 received normal saline by intraperitoneal (ip) injection; group 2 also received ip normal saline, then were submitted to stress, by the cold restraint method; group 3 received a solution of arachidonic acid (AA) ip; and group 4 also received ip AA, then were submitted to stress. After sacrifice, the number of gastric ulcerations were counted and specimens of nonulcerated mucosa were assayed for PGE2 by high-performance liquid chromatography; the mean numbers of ulcers were 0, 5.8, 0.8, and 3 and the mean levels of PGE2 were 55, 41, 125, and 62 pg/mg of wet tissue for groups 1, 2, 3, and 4, respectively. It is concluded that parenteral administration of AA reduces but does not completely eliminate stress-induced gastric ulcerations and that the stressed animals synthesized half as much PGE2 as the nonstressed ones after ip administration of equal amounts of AA, suggesting that stress reduces the availability of AA to the gastric mucosa, possibly by vascular spasm.

Animals↗