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Biomedical subjects

R M Friedman

Publications and source records attributed to R M Friedman.

At least 91 records · Page 5Linked to original sources
PubMed1989

Enhanced in vivo therapeutic response to interferon in mice with an in vitro interferon-resistant B-cell lymphoma.

A stable subline of 38C13 B-cell lymphoma (SIR-1) resistant to the antiproliferative effects of alpha-interferon (IFN) was isolated. In addition to defects in antiproliferative effects of IFN, SIR-1 is defective in IFN-mediated antiviral activity against both encephalomyocarditis virus and vesicularstomatitis virus. It is also defective in the induction of 2'-5'-oligoadenylate synthetase mRNA and enzyme activity, enhancement of H-2 antigen expression, and transient induction and subsequent repression of c-myc by IFN. SIR-1, although completely resistant to IFN in vitro, is more sensitive to IFN than the parental cell line in vivo. IFN treatment at 10(4) units, three times weekly, resulted in a 28% increase in mean survival time and a 1.4% long term survival rate in the IFN-sensitive 38C13 cell line but resulted in a 275% increase in mean survival rate and a 27% long term survival rate in the interferon-resistant SIR-1 mutant. Statistical analysis of 38C13 and SIR-1 with and without IFN treatment demonstrate that: a) the SIR-1 mutant remains sensitive to the cytotoxic effects of IFN in vivo (P less than 0.0001); and b) the mean survival and long term survival of animals with the SIR-1 mutant is significantly greater than for animals with the IFN-sensitive 38C13 cell line (P less than 0.0001). Two additional independently isolated IFN-resistant cell lines (SIR-111 and SIR-E102) also demonstrate significantly enhanced in vivo response to IFN compared to the interferon-sensitive parental (38C13) cells. These results indicate that, for this cell line, the antitumor effects of IFN are mediated by activation of host defenses and that resistance to the in vitro cytotoxic effects of IFN results in a tumor phenotype that is more readily recognized by host defenses and eliminated.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

A research and training needs assessment of Florida's mental health system.

The authors conducted an assessment of mental health training, consultation, and research needs in Florida. The purpose was to document the current training, consultation, and information needs within the mental health care delivery system. The data collection included a six-page, self-administered mail questionnaire and a structured telephone interview of selected key informants throughout the state. The questions on the survey instrument asked for background information on the respondents as well as their training and research priorities for mental health services. Accountability procedures, financing issues, and clinical diagnostic and assessment techniques were among the most frequently rated priorities for training and research. Results are discussed with emphasis on the statewide dissemination of study findings, a national standardization of the needs assessment process, and the importance of systematic decision-making for administrators in the mental health service delivery system.

Evaluation Studies as Topic↗
PubMed1989

A national study of state-supported psychiatric research institutes.

States have funded psychiatric research through a variety of mechanisms, including psychiatric research institutes. The authors identified and surveyed 33 such institutes to obtain information on their organizational characteristics. Twenty-nine institutes responded; more than half were organizationally located within a university setting, and a similar number were involved in research, education, and direct services. Clinical research was the most prevalent type of research conducted, and annual state revenue appropriations were the major source of funding. Because budgetary problems have threatened their future funding in some states, the authors believe the institutes should increase efforts to demonstrate their relevance to state mental health needs.

Academies and Institutes↗
PubMed1989

Cytokines and oncogene activity.

Cytokines play a part in the control of cellular growth, differentiation and development. Given such pleiotropic activities, it is not unexpected that the expression of the cytokines is tightly regulated. When cytokine-mediated processes are altered by mutation and/or overexpression of some cytokine or cytokine receptor genes, oncogenic transformation can occur. Oncogenes which derive their transforming potential through this mechanism include sis, which represents the activated form of the platelet-derived growth factor B chain, hst1/K-fgflint-2, which share appreciable homology with the gene family of fibroblast growth factors, fms, which is related to the cell surface receptor for macrophage-colony stimulating factor, and erbB-1, which encodes a truncated form of the epidermal growth factor receptor. Cytokine treatment has resulted in modulation of aberrant oncogene activity in some model systems.

Animals↗
PubMed1988

Transcriptional inhibition of Ha-ras in interferon-induced revertants of ras-transformed mouse cells.

Elevation in Ha-ras expression, due to transcriptional activation or gene amplification, is associated with oncogenic transformation of NIH 3T3 cells. We have previously shown that murine interferon (IFN)-alpha/beta induced phenotypic reversion of NIH 3T3 cells transformed by long terminal repeat (LTR)-activated c-Ha-ras. The revertants produced decreased amounts of ras-encoded Mr 21,000 protein. We have now determined the molecular level at which LTR-ras regulation occurred. Nuclear run-on experiments revealed a selective inhibition of ras transcription in IFN-treated revertants. There was no apparent additional posttranscriptional control by IFN as judged by the unchanged half-life of ras transcripts. Inhibition of ras RNA synthesis was seen only in conjunction with long-term IFN treatment and was limited to the revertants, a population of cells that maintained sensitivity to IFN during the prolonged exposure. The reduction in ras activity appeared responsible in part for the loss of tumorigenicity in treated cells and was stable for several weeks after treatment had been discontinued.

Animals↗
PubMed1988

Effect of cloned human interferon-alpha 2a on bovine parainfluenza-3 virus. Brief report.

Pretreatment of bovine turbinate (BTu) cells with cloned human interferon (IFN)-alpha 2a reduced the yield of infectious bovine parainfluenza-3 virus (PI-3 V). Intracellular synthesis of HN glycoprotein was reduced on postinfection day 1 (PID 1), but it recovered to normal levels subsequently. However, reduction of this protein persisted in the released virus through PID 2. Thin section electron microscopy demonstrated a drastically reduced release of mature virions and an accumulation of viral nucleocapsids inside the cytoplasm on PID 2. These results suggest that cloned human IFN-alpha 2a affects the glycoprotein synthesis, and morphogenesis of bovine PI-3 V, and thus inhibits the release of viral particles from treated cells.

Animals↗
PubMed1988

Human interferon-gamma protects rhesus monkeys against sporozoite-induced Plasmodium cynomolgi malaria infection.

Earlier we reported that prophylactic treatment with recombinant human interferon gamma (rHuIFN-gamma) for a prolonged duration completely suppressed experimental infection with Plasmodium cynomolgi B sporozoites in rhesus monkeys. We now show that reducing the rHuIFN-gamma treatment to three administrations given close to the time (on days -1, 0, and +1) of infection was sufficient for complete protection. Animals initially protected by rHuIFN-gamma treatment are susceptible to reinfection. Studies are in progress to understand the precise mechanism of protection afforded by HuIFN-gamma against sporozoite-induced malaria infection.

Animals↗
PubMed1988

Interferon inhibits Aspergillus fumigatus growth in mice: an activity against an extracellular infection.

Prophylactic treatment of mice with interferon (IFN) or polyinosinic-polycytidylic acid [poly(I:C)], an IFN inducer, provided significant protection against an extracellular infection by Aspergillus fumigatus in both Swiss and Swiss athymic nude mice. Tunicamycin (TM) treatment inhibits the antifungal activity of IFN and poly(I:C) in these mice. Anti-asialo GM1 or TM [both inhibitors of natural killer (NK) cell function] treatment enhance the severity of A. fumigatus infection. These results suggest that NK cells may play a role in A. fumigatus infection and in the antifungal activity of IFN.

Aspergillosis↗
PubMed1987

Structural proteins of bovine parainfluenza-3 virus.

Six structural proteins of bovine parainfluenza-3 virus (PI-3V) labeled with [35S]-methionine could be resolved by polyacrylamide gel electrophoresis (PAGE). Five structural proteins of this virus had been previously reported. The 6 proteins found in this study were: L, a 180,000 (180 kD) molecular weight (MW) large protein; P, 83 kD phosphoprotein; HN, 69 kD hemagglutinin-neuraminidase glycoprotein; NP, 66 kD nucleocapsid protein; F, 55 kD fusion glycoprotein; and M, 38 kD matrix protein. Selective labeling with [2-3H]-mannose revealed only HN and F glycoprotein bands. A cellular actin protein (43 kD), associated with many enveloped viruses, was also found as a seventh protein in bovine PI-3V.

Animals↗
PubMed1987

Interferon-induced revertants of ras-transformed cells: resistance to transformation by specific oncogenes and retransformation by 5-azacytidine.

Prolonged alpha/beta interferon (IFN-alpha/beta) treatment of NIH 3T3 cells transformed by a long terminal repeat-activated Ha-ras proto-oncogene resulted in revertants that maintained a nontransformed phenotype long after IFN treatment had been discontinued. Cloned persistent revertants (PRs) produced large amounts of the ras-encoded p21 and were refractile to transformation by EJras DNA and by transforming retroviruses which carried the v-Ha-ras, v-Ki-ras, v-abl, or v-fes oncogene. Transient treatment either in vitro or in vivo with cytidine analogs that alter gene expression by inhibiting DNA methylation resulted in transformation of PR, but not of NIH 3T3, cells. The PR retransformants reverted again with IFN, suggesting that DNA methylation is involved in IFN-induced persistent reversion.

Animals↗
PubMed1987

Tunicamycin enhances virus replication and inhibits antiviral activity of interferon in mice: correlation with natural killer cells.

Earlier we reported that tunicamycin (TM) treatment enhances Semliki Forest virus (SFV) and encephalomyocarditis virus (EMCV) replication in Swiss mice. Interferon (IFN) mediated antiviral protection was also inhibited in mice treated with TM. The in vitro natural killer (NK) cell reactivity of mice was significantly decreased after in vivo administration of TM; however, TM treatment did not affect the response of the same cells to mitogens. TM also inhibited the boosting of NK reactivity by IFN in vivo. In this paper, we have shown that depletion of NK cells by asialo-GM1 antiserum enhances SFV/EMCV replication in mice. Both TM and anti-asialo GM1 treatment significantly inhibited the large granular lymphocyte (LGL) populations in the spleen. Similar to Swiss mice, the in vitro NK cell activity of athymic nude mice was significantly decreased after in vivo administration of TM and TM also inhibited the boosting effect on NK cells reactivity induced by IFN in vivo. TM treatment of nude mice also enhanced the SFV/EMCV in brains of infected mice and also inhibited the antiviral activity of IFN in nude mice. These results suggest that NK cells may be involved in SFV/EMCV infection and in antiviral protection afforded by IFN.

Animals↗
PubMed1986

Recombinant human gamma interferon inhibits simian malaria.

Prophylactic treatment with 0.1 mg of human gamma interferon per kg (body weight) per day completely suppressed experimental infection with Plasmodium cynomolgi B sporozoites in rhesus monkeys. Treatment with lower doses partially suppressed this infection. Prophylactic treatment with human gamma interferon, however, had no protective effect against trophozoite-induced infection, suggesting that the interferon effect was limited to the exoerythrocytic stage of parasitic development.

Animals↗