Biomedical subjects
Publications and source records attributed to I H Evans.
The HIS3 gene of the yeast Yarrowia lipolytica has been cloned from a genomic library by complementation of the his3 mutation of Saccharomyces cerevisiae. The gene was subsequently subcloned in Escherichia coli and characterized by restriction enzyme mapping.
Nineteen haploid yeast (Saccharomyces cerevisiae) strains were used to assess the relative growth inhibitory potencies on fermentable vs. non-fermentable media of a collection of carcinogenic and non-carcinogenic chemicals. The majority of carcinogens were distinctly more potent on the non-fermentable (glycerol) medium, where mitochrondrial function is required for growth, than on the fermentable medium, where it is not. The anti-mitochondrial selectivity indicated by these growth tests was much slighter for the non-carcinogens. Similarly most carcinogens induced the cytoplasmic petite mutation whereas the non-carcinogens did not. Five carcinogens which were tested impaired the development of cytochromes aa3 and b in glucose cultures. Six carcinogens, when tested, inhibited growth on three fermentable sugars, the utilisation of which requires mitochondrial function. Out of five carcinogens which were examined, four suppressed the surface-dependent phenomenon of fluocculence in a flocculating strain of yeast, at concentrations primarily affecting the mitochondrial system; the fifth had a similar but less pronounced effect.
Recently developed techniques for the investigation of iron kinetics were used to study the disturbance of iron metabolism in 19 untreated patients with Hodgkin's diseases (HD). The erythroid abnormality in newly diagnosed HD appears to be confined to those patients with systemic symptoms of weight loss, night sweats and fever, and consists of depression of marrow erythroid activity. These patients had a significnatly lower haemoglobin and serum iron concentration and a higher serum ferritin concentration, both when compared to normal subjects and to those patients with HD who lacked systemic symptoms. Ineffective erythropoiesis and red-cell destruction were not significantly increased. The present findings, confirm that HD patients with systemic symptoms have a depression of erythropoiesis, and that in these patients the marrow fails to respond to the stimulus of mild anaemia.
A fluorescence polarisation technique ("S.C.M. test") for detecting responses to phytohaemagglutinin revealed that the responsive lymphocytes from patients with malignant disease had an abnormal distribution after centrifugation through lymphocyte separation medium. In a small blind series the technique accurately distinguished patients with histologically proven malignancies from those with nonmalignant disease and normal people.
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Planned laparotomy and splenectomy has been a safe investigation for sixty patients with clinical Stage I, II or III Hodgkin's disease. Twenty-four of the 60 patients (40%) changed stage and 18 patients had their treatment altered as a consequence of the procedure. Forty-three per cent of patients without a palpably enlarged spleen had unsuspected disease when the organ was examined pathologically, although a false positive spleen was uncommon. Eight of 55 patients (14.5%) had intra-abdominal disease which was not detected by lymphangiography. Intra-abdominal disease occurred with all histological sub-types and was found in two patients who had clinical Stage I disease and lymphocyte predominance in their node histology. Sarcoid-like granulomata were found in ten patients, seven in the spleen, one in the liver and spleen, one in the skin and one in the original node biopsy. In the majority of patients, granulomata were associated with nodular sclerosing or mixed cellular histology. In all ten patients the Hodgkin's disease was suppressed by appropriate chemotherapy and disease has not recurred. No patient has shown any clinical evidence of sarcoidosis and the Kveim test done in three patients was negative. Our experience encourages us to recommend staging laparotomy for all adult patients with Hodgkin's disease which does not show obvious generalized spread beyond lymph nodes.
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Hepatocytes prepared by a simplified enzymatic technique were active in the incorporation of RNA and protein precursors into acid-insoluble material. The incorporation of RNA precursors was very markedly inhibited by low levels of aflatoxin B1 and G1 but not by aflatoxins B2 and G2. The activity of mixed function oxidases (MFO), the drug-metabolizing system of the endoplasmic reticulum, could be suppressed in these cells by SKF525A or stimulated by NADPH. SKF525A caused a reduction in the inhibition by aflatoxin B1 of the incorporation of RNA precursor into macromolecules. This finding suggests that a metabolite of aflatoxin B1 is the actual inhibitor of RNA synthesis in the cells. Measurement of lactate dehydrogenase activity showed these cells to be leaky on incubation at 37 degrees C and thus not suitable for studies of protein secretion.
Liver cells were isolated from rats undergoing active formation of tetraploid cells and prelabelled in their DNA with 14C thymidine. Autoradiography of the isolated cells showed that binucleate diploid cells, a major component of the parenchymal cell population at this time, are also active in DNA synthesis. These cells probably pass through mitosis and generate mononucleate tetraploid cells, the dominant cell type of mature rat liver, since the frequency of binucleate tetraploid cells is very low at this stage in rat liver development. The biological significance of liver polyploidy is discussed and it is suggested that this lies in enhanced resistance to mutagenesis.
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Fifty cases of Hodgkin's disease have been investigated using the lymphocyte transformation response to phytohaemagglutinin (PHA) as a mesure of their immunological reaction. The average response of all the cases was lower than that of the controls and lower than that of cases of carcinoma from all sites. Cases of Hodgkin's disease which had been treated previously with radiotherapy and/or chemotherapy had a markedly lower response than that of the untreated cases. There was no definite correlation between the stage of the disease and the lymphocyte response with PHA. Seven cases were also tested with pokeweek mitogen (PWM) and the response of the lymphocytes to PWM was found to parallel that of the PHA.