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Biomedical subjects

W A Carter

Publications and source records attributed to W A Carter.

At least 127 records · Page 7Linked to original sources
PubMed1971

Comparative production of interferon by human fetal, neonatal, and maternal cells.

Production of interferon was studied in fibroblasts cultured from human fetal, neonatal, and maternal tissue. Human fetal and maternal cells were paired to diminish genetic variability. Fetal cells displayed an increased response to two inducers of interferon, virus and synthetic double-stranded ribopolynucleotide. Fetal cells released 300-fold more interferon than maternal cells on exposure to poly rI:rC. This enhanced capacity for interferon production was consistent in cultures developed from fetal skin obtained between the 10th and 20th gestational week. The response was relatively stable, persisting in cells cultured for 18 generations (about 14 weeks). On infection with Newcastle disease virus, fetal cells produced, on the average, 4 to 6.5 times more interferon than maternal or neonatal cells. The virus was adsorbed with equal efficiency by each type of cell. Increased production is apparently independent of the rates of overall protein synthesis, since fetal and maternal cells have very similar rates of total protein synthesis.

Journal Article↗
PubMed1970

Interferon: evidence for subunit structure.

During the purification of mouse and human interferons, multiple active components have been detected. Mouse interferon was purified over 500-fold by differential precipitation, centrifugation, gel chromatography, and isoelectric focusing. On electrofocusing, two molecular forms (A and B) were noted. Form B (isoelectric point 7.35) had a molecular weight of about 38,000 and Form A (isoelectric point 7.15), which was equally active, a molecular weight of 19,000. Purified Form B was dissociable into Form A, but the reverse reaction occurred to a much lesser extent. Human interferon, purified about 1550-fold, is also composed of multiple molecular forms. Form B (pI 5.60) had a molecular weight of about 24,000 and Form A (pI 5.35), which may contain up to 85% of the total activity, a molecular weight of 12,000. Both forms appear to be equally active. The dissociation of both human and mouse interferons into subunits appears to take place during dialysis versus low salt (0.01 M Tris pH 7.4). The data are consistent with the idea that the native molecule exists as a dimer of similar or identical subunits. Dimer formation, which probably occurs within the cells, does not seem to lead to a measurable cooperative effect between the subunits.

Animals↗
PubMed1967

Ribosomes: effect of interferon on their interaction with rapidly labeled cellular and viral RNA's.

Rapidly labeled RNA of mouse L cells and labeled RNA of Mengo virus, unlike cellular RNA labeled under steady-state conditions, form detectable complexes with L-cell ribosomes. These ribosome-RNA complexes formed in vitro appear analogous to those assembled during polysome formation in vivo. When ribosomes are prepared from L cells exposed to homologous interferon, their capacity to associate with cell messenger is preserved, while their ability to interact with viral RNA is markedly reduced. The ribosomes from cells exposed to interferon are thus altered selectively to permit only certain messages to be bound and translated.

Animals↗
PubMedDate not supplied

Differential effects of human natural interferon-alpha and mismatched double-stranded RNA against a human renal cell carcinoma xenograft.

The antitumor effects of natural human IFN-alpha and mismatched dsRNA against the human renal cell carcinoma cell line 786-0 were studied both in a clonogenic soft agar assay and in the nude mouse. The 786-0 cells were sensitive in vitro to the antiproliferative effects of IFN-alpha in a dose-response manner, up to 3000 IRU/ml. These cells were also sensitive, in a dose-dependent manner, to mismatched dsRNA in the clonogenic assay. Mismatched dsRNA was effective in inhibiting tumor growth (p less than 0.001) in nude mouse xenografts, with regression of the tumor mass seen in all animals. A significant increase in survival (p less than 0.001) was seen in the mismatched dsRNA treated group. In contrast, IFN-alpha did not inhibit tumor growth in vivo, even though significant titers of IFN-alpha (greater than 3,000 IRU/ml) were found in the serum shortly after treatment. Mismatched dsRNA did not induce the production of human IFNs by the tumor cells in vitro. Assays of mouse IFN induction and their in vitro antigrowth effects indicated that the in vivo antiproliferative effect of mismatched dsRNA was probably not due to potentiation of any direct effects by the induced mouse IFNs. Tumor growth inhibition appeared to occur, at least in part, from the significant augmentation (p less than 0.01) of natural killer cell activity by mismatched dsRNA, as measured in the spleen cells of treated mice. These results suggest that, although both IFN-alpha and mismatched dsRNA can be directly antiproliferative against this tumor, either the IFN-independent antitumor effects of mismatched dsRNA or the mismatched dsRNA-induced augmentation of the host immune response plays a major role in tumor regression. Potentially, both mechanisms may be important in this system.

Animals↗
PubMedDate not supplied

The search for "virogene" in human prostatic tissues: prostatic DNA polymerases.

The "virogene-oncogene" hypothesis of Huebner and Todaro and the "provirus" hypothesis of Temin implicate RNA tumor viruses in the neoplastic transformation of mammalian cells. These hypotheses have been substantiated in several animal systems including primates and, presumably, in man. Because the detection in a tissue of one or two activities allegedly related to RNA tumor virus may not be conclusive evidence for viral presence, we have developed a scheme of coordinated morphologic, biologic, and biochemical investigations of human prostatic tissues. We report here the more recent progress we have made in one of the segments of our scheme of investigations. Two, possibly three, DNA polymerase activities from human prostatic tissue have been isolated and partially purified by DEAE-cellulose and phosphocellulose chromatography. These activities have been partially characterized. Based on template preferences and non-inhibition by selective inhibitors of reverse transcriptase, neither of the major polymerase activities appears to be the reverse transcriptase-type activity.

Adenine↗
PubMedDate not supplied

RNA tumor virus-like activities in human prostate: possible novel pharmacologic approaches.

The cytoplasmic extracts of human prostatic tissues yield two classes of "particles" when centrifuged to equilibrium in a sucrose density gradient, one class banding at a density of 1.15-1.18 g/cm3 ("high density particles") and another at a density of 1.07-1.14 g/cm3 ("low density particles"). Both bands display endogenous DNA polymerase activity which is largely resistant to actinomycin D inhibition. The endogenous DNA products synthesized by high density particles give some indication of high molecular weight RNA:DNA complexes. The tissue extracts from normal, hyperplastic, and neoplastic prostate behave similarly in these assays. In addition, explant cultures of hyperplastic and neoplastic prostate either release, or can be induced to release, particles by treatment with bromodeoxyuridine. These particles band at a density of 1.15-1.18 g/cm3 in a sucrose density gradient and possess RNA and associated DNA polymerase activity which utilizes poly(A):oligo(dT). Our results suggest that human prostatic tissues may contain functions analogous in some ways to those of known RNA tumor viruses of other species.

Bromodeoxyuridine↗