Publications by authors named "Clark I"

Rats with aflatoxin-B1-induced hepatomas and dimethylnitrosamine-induced nephroblastomas excreted greater than normal amounts of urinary modified nucleosides and bases, catabolites of ribonucleic acid (RNA). Although both neoplasms caused increased excretions of the same catabolites, their quantitative profiles differed, suggesting that it may be possible to distinguish between tumors. Rats with transplanted tumors (e.

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Intravenous injection of divicine into mice infected with Plasmodium vinckei rapidly killed the parasites and caused haemolysis. Degenerating parasites were observed frequently inside intact circulating erythrocytes, implying that parasite death was not a passive consequence of haemolysis. Both parasite death and haemolysis were prevented by the iron chelator desferrioxamine.

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Serum from mice infected with Babesia microti or Plasmodium vinckei petteri and given lipopolysaccharide (LPS) contained appreciable amounts of tumour necrosis factor (TNF) and lymphocyte-activating factor (LAF; Interleukin I) activity. These monokines were not noted in serum from uninfected mice given the same dose of LPS. This pattern was repeated when adherent peritoneal cells from normal or infected mice were exposed to LPS in vitro and the supernatants assayed for LAF.

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Intravenous injection of t-butyl hydroperoxide rapidly killed Plasmodium vinckei in mice, and caused haemolysis. The same dose seemed harmless to unparasitized mice. Many parasites disintegrated inside circulating erythrocytes, so parasite death was not simply a passive consequence of haemolysis.

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Rats with transplants of Morris Hepatoma 5123 excreted in their urine greater than normal amounts of modified nucleosides and bases, catabolites of RNA. Despite rapid growth of the neoplasm, the elevated levels did not appear until 22 days after inoculation with the tumor. With tumor progression, there were increased levels and number of these catabolites.

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The primary disturbance in Duchenne muscular dystrophy (DMD) appears to affect membrane function, and changes characteristic of oxidant-induced damage occur in skeletal muscle and erythrocytes. There is recent evidence that DMD is a functional tocopherol deficiency, with reduced levels of the lipoprotein required to carry tocopherol to tissues. This may explain the parallels between DMD and dietary tocopherol deficiency.

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This study describes effects of aflatoxin B1-induced hepatomas on RNA metabolism in rats. At 4 and 24 hours after the administration of L-(14CH3)-methionine, tRNA was isolated from the livers and hydrolyzed enzymatically to nucleosides which were quantitatively measured by HPLC. Radioactivity of the nucleosides was also determined.

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Mice injected with Propionibacterium acnes, when challenged with lipopolysaccharide release a range of soluble mediators into their serum. Included among these is lymphocyte activating factor (LAF, interleukin-1). The release of LAF in vivo was detected only when serum samples were assayed at high dilution because inhibitors of its activity in vitro were also present.

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A rapid reduction in parasitemia associated with damage to intraerythrocytic parasites was observed in Plasmodium vinckei-infected mice after they had received a single intravenous injection of alloxan. This was not prevented by prior injection of glucose, but was prevented by desferrioxamine or diethyldithiocarbamate. Prior injection of propanol partially blocked the phenomenon.

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Hepatomas were induced in rats with aflatoxin B1, and nephroblastomas with dimethylnitrosamine. Microscopic examination of livers of aflatoxin-treated rats revealed multinodular hepatocyte hyperplasia at 8 months, and by 13 months all rats had hepatomas. Nephroblastomas were observed by 4 months and by 8 months all rats had developed them.

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Increased natural killer (NK) cell activity was found in the spleen and peritoneal cavity of mice infected with Babesia microti or Plasmodium vinckei petteri. This increased activity appeared not to be associated with the effectiveness of the host response against these parasites, since it reached its maximum when the parasitaemia was still low, and had decreased by the time the parasites reached peak densities. In addition mice pretreated with 89Strontium of 17 beta-oestradiol experienced the same pattern of infection as did control mice, yet the infections induced much lower levels of NK activity in the pretreated mice.

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The mechanics of the metacarpophalangeal joint are analyzed, with a view to understanding why the finger moves in the direction of ulnar drift when the intra-articular pressure in the joint is increased. The first step is the in situ measurement of stiffness of the various tissues surrounding the joint, and the data show that (a) the two collateral ligaments are the major component and (b) the ulnar ligament is the stiffer. This latter result, combined with finding the centre of pressure at the base of the phalanx, reveals how increased intra-articular pressure produces ulnar deviation.

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Using various strains of inbred mice, we found that Propionibacterium acnes-induced protection against the hemoprotozoan parasite Babesia microti was controlled by a dominant gene(s) not linked to the major histocompatibility gene (H2) complex of mice. P. acnes-induced resistance to infection was not merely an amplification of the normal immune response to B.

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Adult (185g) rats are about twice as sensitive to the harmful effects of injected endotoxin as are younger (65g) rats. This relationship correlates with an earlier report on the densities of Plasmodium berghei at which deaths occur in rats of these two age groups. Similarly lizards, which withstand very high parasitaemias of malaria parasites, are refractory to very large doses of endotoxin.

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Malarial parasites, Plasmodium vinckei petteri, taken from lipopolysaccharide (LPS) high-responder (C3H/HeJGiFWeHi) mice which had been injected 7 to 8 h previously with either Escherichia coli LPS B or LPS W incorporated the purine nucleotide precursor hypoxanthine more slowly in an in vitro assay than parasites taken from saline-injected controls. In contrast, malarial parasites taken from LPS low-responder C3H/HeJ mice after injection of either LPS B or LPS W did not show reduced levels of hypoxanthine incorporation. These differing results with LPS high- and low-responder mouse strains demonstrated that the cytostatic effect on the parasites seen in the high-responder strain was not due to the direct action of LPS and implied that the cytostasis was mediated via host lymphoreticular cells.

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In an in vitro assay, malarial parasites (Plasmodium vinckei petteri) taken from mice 7 to 8 h after the injection of bacterial lipopolysaccharide (LPS) incorporated significantly less hypoxanthine into nucleic acid than did parasites from saline-treated controls. In contrast, incorporation was normal in parasites taken from mice within minutes of the injection of LPS and in parasites cultured with LPS. These results implied that the injection of LPS induced the release of mediators with a cytostatic effect on the parasite.

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The effects of a high-phosphate diet on the calcium metabolism of kidney cells were studied in intact and parathyroidectomized (PTX) rats. The control and the PTX rats were pair-fed a normal diet with a Ca/P of 2:1 or a high-phosphate diet with a Ca/P of 1:8 for 6 wk (chronic experiments) or 1, 3, and 6 days (acute experiments). Renal cell calcium metabolism was studied by chemical and kinetic analyses in kidney slices incubated in vitro.

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