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W J Kleinschmidt

Publications and source records attributed to W J Kleinschmidt.

17 recordsLinked to original sources
PubMed1982

Similarities of murine gamma interferon and the lymphokine that renders macrophages cytotoxic.

Murine spleen lymphoid cells treated with insoluble (Sepharose bound) concanavalin A elaborate Gamma (immune) interferon (IFN-gamma) and macrophage activation factor (MAF) into the culture medium. Similarly, MAF is produced by T cells with other IFN-gamma inducers. MAF induces resting (noncytotoxic) macrophages to become tumoricidal. We have compared various physicochemical properties of MAF and INF-gamma, their neutralization by antibody to IFN-gamma, and their induction period. In these parameters, induction of antiviral activity was compared to induction of macrophage tumoricidal activity. All of the parameters studied have given results that demonstrate close similarity in the physical properties, molecular characteristics, and biological reactivities of the two lymphokines, and this similarity suggests that these two lymphokines reside in the same molecule. This conclusion would include that IFN-gamma, like IFN-alpha and IFN-beta, is capable of activating macrophages to become cytotoxic toward tumor cells.

Animals↗
PubMed1982

Interferon induction and macrophage activation by a mycovirus double-stranded RNA/tobramycin complex following treatment with human serum.

Double-stranded RNA (dsRNA) molecules, generally effective inducers of interferon (IFN), have a weak potency in man apparently because of the presence of a serum RNAase which quickly inactivates extracellular dsRNA. We have discovered that tobramycin, an aminoglycoside, protects Penicillium chrysogenum mycovirus dsRNA (PCMdsRNA) from the degradative action of the nuclease. Exposure of the dsRNA/tobramycin complex to human serum results in some degradation, but still permits the production of significantly high titers of IFN upon injection into mice. Intraperitoneal (i.p.) treatment of CFI mice with both dsRNA and dsRNA/tobramycin complex activated macrophages to inhibit the growth of P815 mastocytoma target cells. Following in vitro treatment with human serum, free dsRNA failed to activate peritoneal macrophages in vivo under conditions where this activity of dsRNA/tobramycin complex was retained. By varying the ratio of moles of tobramycin (as free base) to the moles of RNA phosphorous, toxicity can be minimized, while retaining the biologic activities of dsRNA.

Animals↗
PubMed1977

Lack of effect on cyclic GMP content of cells treated with mycophenolic acid.

Mycophenolic acid, an oncolytic agent and a known inhibitor of guanine ribonucleotide synthesis, has proven to be an effective drug against psoriasis. With reports of greater guantities of c-GMP in psoriatic tissues than in normal tissue, and with the correlation of c-GMP content of cells to proliferation, the effect of mycophenolic acid on cellular c-GMP was investigated. When HeLa, green monkey BSC-1, and mouse L-cells were treated with inhibitory concentrations of mycophenolic acid, no decrease in c-GMP was observed from that of untreated cells. Though mycophenolic acid inhibits guanine ribonucleotide synthesis, this inhibition does not extend to c-GMP synthesis. The inhibition of proliferation of cells by mycophenolic acid then does not include the inhibition of synthesis of c-GMP, but apparently resides solely in limiting the guanylate necessary for nucleic acid synthesis.

Cell Count↗
PubMed1971

Inhibition of influenza virus and interferon response intranasally with statolon.

Statolon, an interferon inducer, when instilled intranasally (IN) protects mice infected with lethal doses of influenza virus via the same route 16 hr later. The existence of interferon has been demonstrated in the trachea and lungs of mice treated IN with statolon, and it is assumed that the protection observed is due to this inhibitor. A dose response is seen with statolon administered IN. The protective activity of statolon instilled IN prophylactically lasts 1 to 2 weeks against influenza virus. Repeated doses of statolon, as many as four, a week apart, are effective. Antigenicity of the statolon (mycophage) particle relative to neutralization of its interferon-inducing capacity, therefore, may not prove to be a problem in clinical testing of this type of interferon inducer. The observed duration of activity of statolon also eliminates the possibility of difficulty due to hyporeactivity of the inducer.

Administration, Intranasal↗
PubMedDate not supplied

Functional identity between murine gamma interferon and macrophage activating factor.

We have previously suggested that two lymphokine activities-macrophage activating factor (MAF) and gamma interferon (IFN-gamma)-are mediated by the same molecule. Striking similarities were noted in their cellular biosynthesis, rate of inactivation with acid treatment and heating, and elution profiles on Sephacryl S-200. In addition, highly specific polyclonal antibodies to murine IFN-gamma neutralized MAF and IFN-gamma to a similar degree. However, definitive studies require a pure product and we now report that murine IFN-gamma that had been cloned and expressed in a simian nonlymphoid cell line shows MAF activity. But it is not yet known whether IFN-gamma is responsible for all the MAF activity in media conditioned by T cells as the possibility for MAF heterogeneity remains.

Animals↗