Interaction of dietary carbohydrate and glucagon in regulation of rat hepatic messenger ribonucleic acid S14 expression: role of circadian factors and 3',5'-cyclic adenosine monophosphate

The mRNA of the rat hepatic S14 gene accumulates rapidly after administration of T3 and carbohydrate, making it an excellent model for studies of the effects of dietary and hormonal stimuli at the hepatocellular level. We undertook studies to assess circadian changes in responsivity of this sequence to intragastric sucrose administration combined with insulin injection, and evaluated the capacity of glucagon to reverse these effects. As in the case of T3, the response of mRNA-S14 to carbohydrate in the morning was brisk whereas there was no significant increment when the stimulus was applied in the evening. In confirmation of previous studies, glucagon markedly lowered levels of mRNA-S14 in the evening but exerted no effect in the morning. These results support the concept that the rate of hepatic production of mRNA-S14 in unmanipulated rats is maximal in the evening, thus allowing no further induction by carbohydrate or T3 but permitting reduction by glucagon. Conversely, the rate of production is minimal in the morning, permitting induction by carbohydrate or T3 but allowing no further reduction by glucagon. A major difference between the effects of carbohydrate and those of T3 was the observed failure of carbohydrate to reverse the effect of glucagon in the evening. The effect of glucagon was stimulated by (Bu)2cAMP, and this was reversed by T3. However, T3 did not modify the glucagon-induced increase in hepatic cAMP levels. We therefore conclude that the capacity of T3 to abolish the glucagon effect is mediated at a step distal to the generation of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of transplantable tumors by adoptive transfer of spleen cells from immunized rats.

Fischer 344 rats were specifically hyperimmunized with allogeneic, nonvirus-producing [Kirsten murine sarcoma virus (KiMSV)] or syngeneic, virus-producing [KiMSV (Rasheed)] rat tumors. Spleen cells taken from these rats adoptively transferred protection against a 100 to 1,000 X rat tumor dose50 cell challenge with several different transplantable rat tumors. Protection was obtained with spleen cells after removal of adherent cells and macrophages but not peritoneal cells. The spleen cells were not directly cytotoxic but required more than 3 days residence in the recipient before protecting the recipient against challenge. No protection against tumor cell challenge was observed when spleen cells were lethally x-ray irradiated before injection into nontreated rats. Spleen cells taken from rats immunized with normal histocompatibility antigens did not protect in this test system.     

The Resident's View of Residency Training in Canada

In the view of residents in their last year of specialty training, the Fellowship is now becoming the operative standard for obtaining hospital privileges in urban centres and they felt that this implied that the two standards, the Certificate and the Fellowship of the Royal College, were not achieving the purpose for which they were designed. Although 80% of the residents intended to write the Fellowship, few viewed a year in a basic science department or in research as of intrinsic value in terms of their future practice.The examinations of the Royal College were the subject of criticism, most residents feeling that the examinations did not test the knowledge and ability gained in training. Most expressed a desire for ongoing evaluation during the training period.Service responsibilities were generally regarded as too heavy.Despite the criticism of both training and examination, most residents felt that their training had provided them with the experience and background they needed to practise as specialists.     

Anomalous behavior of goldfish IgM heavy chain in sodium dodecylsulfate polyacrylamide gel electrophoresis

By sodium dodecylsulfate polyacrylamide gel electrophoresis, the heavy chain of the serum immunoglobulin (IgM) of the goldfish (Carassius auratus) differs not only from other studied vertebrate serum IgM heavy chains, but also from other vertebrate lymphocyte membrane IgM heavy chains including those from the goldfish itself. This difference, an increase in apparent Mr of approximately 5000, was investigated by assessing in comparison with the IgM heavy chain of human and rainbow trout (Salmo gairdneri) the following properties: (1) molecular size by gel filtration in denaturing buffers; (2) carbohydrate content, by direct analysis; (3) intrinsic net charge, by isoelectric focusing; (4) net hydrophobicity, deduced from amino acid analysis; and (5) sodium dodecylsulfate binding by direct measurement. Results indicate that goldfish IgM heavy chain is indistinguishable from other IgM heavy chains in terms of (a) its gel-filtration behavior in denaturing conditions, (b) its carbohydrate content (which is similar to trout IgM heavy chain) and (c) its intrinsic net charge and hydrophobicity. However, goldfish IgM does differ from the other proteins studied in its detergent-binding ability and it is this behavior that is concluded to be the cause of its unusual mobility in sodium dodecylsulfate polyacrylamide gel electrophoresis.     

Changes in enzyme specific activity and isoenzyme distribution patterns of L cells as a function of growth conditions

Summary The parent and two subclones of the L-M cell line were grown in shake, spinner, and monolayer culture in the presence or absence of 10% bovine serum and assayed to determine the effect of different cultural conditions upon enzyme activity. The assay variability itself was 5 to 13%. Growth of duplicate cultures and independent processing increased the over-all variability to 13 to 48%, depending upon which enzyme was being assayed. Lactic dehydrogenase activity was 2-fold greater and malic dehydrogenase activity was 3-fold greater in spinner culture than in shake culture. Zymograms from serum-free spinner cultures showed the characteristic clonal differences reported previously (6); however, no differences were observed among the cells grown in monolayer or shake culture. The presence of 10% bovine serum markedly lowered the generation time of shake cultures and also lowered the specific activities of three enzymes. This lowering of enzyme specific activity was moderated depending upon the method of cell culture. The physical and nutritional environment of the cell greatly affects its enzyme activity.     

A Pilot Study of Applications to the Four Ontario Medical Schools for Admission to the First Professional Year

In the fall of 1964, newspaper accounts of the medical school applicant situation in Canada reported that hundreds of fully qualified applicants were being turned away because of shortage of places. Such reports precipitated a pilot study of the applications received by the four Ontario medical schools for the first professional year of medicine and it was found, first of all, that the total of 1352 applications represented only 880 individuals. Nearly 32% of these applicants were American and 18% were citizens of Commonwealth or other countries. While a majority of the applicants met the minimal requirements of the schools, very few of the rejected applicants had academic records that justified admission when the informal standards of the schools were applied. It was concluded that it is erroneous to speak of a surplus of well-qualified applicants at the present time and that the need for recruiting programs still remains.