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Biomedical subjects

E W Parry

Publications and source records attributed to E W Parry.

At least 37 records · Page 2Linked to original sources
PubMed1984

Cycloheximide challenge of mice bearing subcutaneous tumours, with observations on heparin treatment.

Mice bearing large subcutaneous transplants of ovarian teratocarcinoma succumb when given large doses of cycloheximide, whereas animals with equally large subcutaneous Ehrlich tumours are resistant to this treatment. Adequate dosage of heparin is life-saving in cycloheximide-treated, teratoma-bearing mice. The results are discussed in the context of previous work, and one tentative suggestion made is that cycloheximide interferes with the mechanism for release of endogenous heparin which is an essential component of the host response to a growing teratocarcinoma.

Animals↗
PubMed1984

A lethal syndrome in mice following administration of carbon tetrachloride and cycloheximide, and its prevention by heparin treatment.

When a hepatotoxic dose of CCl4 is followed in 6 h (but not in 18 h) by 30 micrograms per g body weight of cycloheximide, a lethal, shock-like state develops. This is prevented by heparin treatment. This lethal syndrome is compared with other, similar, induced lethal states in which cycloheximide plays an essential role, and in which heparin is lifesaving. It is postulated that, after CCl4, a phase of procoagulant activity occurs in the dying centrilobular zone hepatocytes, but that unimpaired protein synthesis permits responsive release of endogenous heparin and thereby prevents thrombosis in centrilobular sinusoids. Cycloheximide is thought to inhibit this heparin release and to allow a transient episode of occlusive centrilobular microthrombosis with consequent irreversible ischaemic damage to the mid-gut.

Animals↗
PubMed1981

Cycloheximide treatment modifies the pattern of "metastasis" following intravenous injection of Ehrlich ascites tumour cells.

Cyclohexamide treatment of recipient mice at various times in relation to an intravenous injection of Ehrlich ascites tumor cells alters the pattern of consequent "metastatic" disease as compared with the pattern in untreated, tumour-injected animals. Analysis of the results suggests the existence of a cycloheximide-sensitive host mechanism for eliminating arrested tumour cells. This mechanism could play an important role in determining the ultimate localisation pattern of neoplastic disease following an intravenous injection of Ehrlich tumour cells.

Animals↗
PubMed1980

The effect of intravenously injected Ehrlich ascites tumour cells in cycloheximide-treated mice.

An intravenous injection of 5 X 10(6) washed, viable Ehrlich ascites tumour cells given to mice 2 hr before, immediately before, or 2 hr after a dose of 60 microgram/g body weight of cycloheximide, results in such animals being either dead or moribund 48 hr later. No fatalities occur when a similar number of tumour cells are given 2 hr before or 2 hr after a dose of 30 microgram/g body weight of cycloheximide. Similarly, 5 X 10(6) tumour cells are well tolerated when given to mice 18 hr after 60 microgram/g cycloheximide. It is suggested that an undefined minimum level of recipient protein synthesis is required for maintenance of life in the presence of a challenge by 5 X 10(6) tumour cells. A minimum period (less than 6 hr) is needed for an irreversible illness to result from interaction of tumour cells with a recipient animal under the maximal influence of the 60 microgram/g dose of cycloheximide. The irreversible illness is not avoided by the use of tumour cells pretreated for 2 hr with 30 microgram/g of cycloheximide, nor is the outcome altered when both recipient and tumour cells are together subjected to a 60 microgram/g dose of cycloheximide.

Animals↗
PubMed1980

The effect of cycloheximide and carbon tetrachloride in Ehrlich ascites tumour-bearing mice.

Treatment with cycloheximide and a hepatotoxic dose of CCl4 (well tolerated in normal animals) is acutely toxic in animals bearing the Ehrlich ascites tumour. Reduction in tumour load 4 hr after the administration of cycloheximide and CCl4 is life-saving: treatment with a hepatotoxic dose of CCl4 30 hr before challenge with cycloheximide and CCl4 also nullifies that otherwise life-threatening treatment.

Animals↗
PubMed1979

Inhibition by cell-free Ehrlich ascites tumour fluid of the resolution of carbon tetrachloride-induced hepatorenal necrosis in mice.

Small doses of cell-free Ehrlich ascites fluid given to mice 18 hr after CCl4 effectively prevents resolution of the toxin-induced hepatorenal necrosis, thus duplicating the reported effects of washed Ehrlich tumour cells. The available data indicate that Ehrlich tumour fluid does not contain the agent directly responsible for resolution-inhibition, but rather contains an inducer which stimulates host tissues to form the ultimate inhibitor. Only in the presence of renal tubular necrosis is the inhibitor allowed to accumulate to levels which prevent resolution. The possibility that host-derived inhibitors include antiproteases is discussed.

Acute Kidney Injury↗
PubMed1978

Effect of Ehrlich ascites tumour on the clinical course and pathology of mice having carbon tetrachloride-induced hepato-renal necrosis.

Ehrlich ascites tumour, administered intraperitoneally 18 hr following a dose of CCl4 by stomach tube, produces and irreversible illness characterised by failure to resolve extensive hepato-renal necrosis. Equally extensive hepato-renal necrosis occurs in animals given CCl4 and saline; such animals, however, remain clinically well and show rapid histological regeneration of both organs. Carbon tetrachloride given to mice on day 5 of tumour growth produces hepatic necrosis only, the kidney of such animals being immune to the necrotising effect of CCl4. Such animals remain well, and histological recovery of the liver is rapid. It is proposed that the Ehrlich tumour produces a "regeneration-inhibiting" toxin, active against the damaged liver and kidney; the CCl4-damaged kidney fails to excrete this toxin, hence the irreversibility of hepato-renal damage and a fatal outcome. A marked reduction of ascites volume as compared with controls was observed in those animals given Ehrlich tumour 18 hr after CCl4, but not in animals given CCl4 on day 5 of Ehrlich ascites tumour growth.

Animals↗
PubMed1977

Differentiation by colchicine and vincristine sulphate of regenerative hepatocellular mitosis and tumour-associated hepatocellular mitosis.

Colchicine and vincristine sulphate differentiate sharply between hepatocyte mitosis associated with the Ehrlich ascites tumour, and regenerative (post-CCl4 necrosis) hepatocyte mitosis. In the former case there is a gross depression of prophase index and a marked lowering of the overall mitotic index. In the latter, although a degree of prophase depression is evident, this is insufficient to prevent an overall substantial elevation of mitotic index due to accumulation at metaphase. Very low doses of colchicine claimed to be effective in stathmokinesis of hepatocytes under influence of hepatomitogenic tumour brei and tumour extracts, produced no discernible effect on the mitotic pattern of hepatocytes in Ehrlich ascites tumour-bearing mice nor in post-CCl4 regenerating livers. The results are discussed in the context of known features of tumour-associated hepatocellular mitosis.

Animals↗
PubMed1976

Tumour-associated hepatocellular mitosis in Ehrlich ascites tumour-bearing mice.

The hepatocellular mitotic response associated with Ehrlich ascites tumour is mediated by the tumour less than 48 hr, but more than 18 hr prior to the time of observation (day 8 of tumour growth). Tumour-associated hepatocellular motisis is normally centrilobular in distribution and appears to involve marginally more of the liver lobule than is sensitive to the necrotic effect of CCl4. There is failure to summate mitotic activity when both tumour-associated hepatocellular mitosis and regenerative hepatocyte motisis would be expected to occur; in this situation regenreative heaptocyte mitosis is the overwhelming contributor to the observed mitotic index. It is postulated that tumour-associated hepatocellular mitosis is obligatorily centrilobular. Tumour-associated hepatocellular mitosis, on the evidence of the present work and the results of others using intraperitoneally administered proteolytic enzymes as inducers of hepatocyte mitosis, is considered to be systematically mediated; there is complete failure to observe any perilobar preponderance of mitotic activity. This implies an indirect effect of tumour in producing the hepatocyte mitogen. Criteria obtained from the present work are suggested as useful in any attempt to isolate and identify the true or in vivo tumour-associated mitogen, and would help to exclude possible non-specific mitogens.

Animals↗
PubMed1975

Induction of hepatocellular mitosis with carbon tetrachloride in late-phase Ehrlich ascites tumour-bearing mice.

Hepatocellular mitoses are scanty or absent in livers of animals in the late stages of growth of Ehrlich ascites tumours. The challenge of CCl4-induced liver necrosis in such animals is, however, met by a massive hepatocellular mitotic response. Thus general debility of the animal, imposing a block on liver cell division cannot be an explantation for the cessation of tumour-associated liver cell mitosis in late-stage tumour-bearing animals. Possible explantations for the pattern of hepatocellular mitosis in relation to duration of tumour growth are discussed.

Animals↗