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Biomedical subjects

R A Clark

Publications and source records attributed to R A Clark.

At least 451 records · Page 25Linked to original sources
PubMed1975

Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system.

A cytotoxic effect of human neutrophils on mammalian tumor cells is demonstrated. Cytotoxicity depends on the presence of intact neutrophils, phagocytosable particles, and a halide cofactor and is inhibited by azide, cyanide, and catalase. Neutrophils from patients with myeloperoxidase (MPO) deficiency or defective H1O2 production are not cytotoxic, but activity is resotred by addition of purified MPO or H2O2 respectively. The findings support a mechanism involving the phagocytosis-induced extracellular release of MPO and H2O2 and their reation with a halide cofactor to damage the target cells.

Animals↗
PubMed1975

Defective neutrophil chemotaxis with variant ichthyosis, hyperimmunoglobulinemia E, and recurrent infections.

Host defense mechanisms were evaluated in a 4-1/2-year-old boy with recurrent pyogenic infections and a unique hyperkeratotic skin disorder. The patient's neutrophils were consistently defective in chemotactic responsiveness but had normal NBT reduction, glucose oxidation, and iodination. Serum concentrations of IgE were markedly elevated and the secondary antibody response was abnormal. No T-cell dysfunction was detected. These findings suggest a relationship between this patient and patients with other syndromes associated with recurrent infections, cutaneous disease, defective chemotaxis, immunodeficiency, and hyperimmunoglobulinemia E.

Chemotaxis↗
PubMed1975

Experimental pneumococcal meningitis: III. Chemotactic activity in cerebrospinal fluid.

Chemotactic activity was assayed in CSF of rabbits with pneumococcal meningitis to further characterize the inflammatory response in this infection. CSF chemotactic activity was detected in increasing levels for 72 hr after infection. Activity was stable at 56 degrees and was inactivated by agents which denature proteins. Gel filtration demonstrated two chemotactically active fractions in infected CSF with mol wts of approximately 3000 and 11,000. Bacterial products appear to account for a portion of the observed CSF chemotactic activity, but the role of host factors remains to be clarified.

Animals↗
PubMed1975

Peroxidase-H2O2-halide system: Cytotoxic effect on mammalian tumor cells.

Myeloperoxidase, H2O2, and a halide constitute a potent antimicrobial system. A cytotoxic effect of this system on a line of mouse ascitic lymphoma cells (LSTRA) is demonstrated here using four different assay systems: 51Cr release, trypan blue exclusion, inhibition of glucose C-1 oxidation, and loss of oncogenicity for mice. Deletion of each component of the system, preheating the peroxidase, or addition of azide, cyanide, or catalase abolished the cytotoxicity. Myeloperoxidase was effective with either chloride or iodide as the halide, while lastoperoxidase was effective with iodide but not chloride. The iodinated thyroid hormones, triiodothyronine and thyroxine, could substitute for the halide, and H2O2 could be replaced by a peroxide-generating enzyme system such as glucose and glucose oxidase or by H2O2 producing bacteria such as pneumococci or streptococci. The possibility is raised that the peroxidases of inflammatory cells and certain biologic fluids may affect tumor initiation or growth in vivo.

Animals↗
PubMed1975

Hemolysis and iodination of erythrocyte components by a myeloperoxidase-mediated system.

Erythrocytes are hemolyzed by myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase; hypoxanthine + xanthine oxidase) and an oxidizable cofactor (chloride, iodide, thyroxine, triiodothyronine). The combined effect of chloride and either iodide or the thyroid hormones is greater than additive. Myeloperoxidase can be replaced by lactoperoxidase in the iodide-, thyroxine and triiodothyronine-dependent, but not in the chloride-dependent, systems. Hemolysis is is inhibited by the peroxidase inhibitors, azide and cyanide, and by catalase and is stimulated by superoxide dismutase when the xanthine oxidase system is employed as the source of H2O2. Hemolysis by the iodide-dependent system is associated with the iodination of erythrocyte components.

Animals↗