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Biomedical subjects

I Karlberg

Publications and source records attributed to I Karlberg.

86 records · Page 5Linked to original sources

Unicellular or multicellular origin of human T-lymphocyte colonies in soft agar?

Human peripheral lymphocytes were cultivated in soft agar or agarose, containing 3H-thymidine or bromodeoxyuridine (BrdU), which is an analogue of thymidine readily incorporated into deoxyribonucleic acid by lymphocytes. Colonies were isolated and analysed by autoradiography or stained with the fluorescence-plus-Giemsa technique, which identifies cells that have passed one, two, three, or more replication cycles with incorporation of BrdU. Colonies contained cells in their first and second division cycle together with later generations. The labelling index was very high. Consequently, it was concluded that, at least without special precautions being taken, lymphocyte colonies in semi-liquid medium are likely to grow through recruitment of mobile cells as well as through divisions within the colonies. Thus, T-cell growth in gels seems to be a matter of recognition between activated blast cells rather than monoclonal growth.

Agar↗

Role of aerobic conditions in the control of cell proliferation.

Our experiments demonstrate that proliferation of human lymphocytes as well as fibroblasts is inhibited by oxygen. It is not a toxic effect and it has been possible to find an intermediary link in intracellular glycolysis, oxidate metabolism, or macromolecule synthesis. Accessory cells may reduce the inhibitory action of oxygen, thereby exerting an influence on the growth rate. In view of recent hypotheses on the mediation of hormone effects via a membrane dehydrogenase system our results may indicate that also the mitotic activation is dependent on the redox state of the membrane for the function of a proton gradient across the plasma membrane itself, delivering energy for glucose and amino acid transport.

Aerobiosis↗

Evaluation of anorexia as the cause of altered protein synthesis in skeletal muscles from nongrowing mice with sarcoma.

The importance of decreased food intake as the mechanism behind altered protein metabolism in skeletal muscle in cancer was evaluated. A methylcholanthrene-induced sarcoma (MCG 101) transplanted in weight-stable and nongrowing mice (C57BL/6J) was used as the tumor-animal model. Three study groups with appropriate control groups were used: sarcoma-bearing mice; pair-fed mice; and starved mice. The synthesis of myofibrillar and sarcoplasmic proteins was decreased in sarcoma-bearing mice. This was correlated to decreased content of RNA in the muscles and caused a net loss of muscle tissue was measured by dry weight of skeletal muscles. The incorporation rate of amino acids into myofibrillar and sarcoplasmic proteins was decreased to the same extent in the pair-fed mice as that in the sarcoma-bearing mice. This probably reflected decreased protein synthesis, since the radioactivity (dpm/mg) did not differ significantly in the crude transfer RNA fraction between the groups. Separation of soluble proteins from muscle tissue by means of ion-exchange chromatography showed that the pattern of decreased protein synthesis was not tumor specific when compared to muscle affected by starvation. The decrease in protein synthesis was more or less selective, since the synthesis of basic proteins was considerably decreased and was influenced more than were neutral and acidic proteins in both cancer and starvation. Anorexia of a tumor-bearing host is a sufficient trigger to induce decreased protein synthesis in skeletal muscles, but other factors may also be of quantitative importance.

Animals↗

Acute alcoholic cholestasis. Report of a case with in vitro studies of hepatic protein synthesis.

A patient is reported who developed acute cholestasis after alcohol abuse. Extrahepatic cholestasis was excluded at laparotomy. Liver microscopy showed cholestasis with slight parenchymal damage but was otherwise normal. In vitro measurements of hepatic protein synthesis indicated increased synthesizing capacity. This is the fourth reported case of so-called acute alcoholic cholestasis.

Acute Disease↗

Metabolism in peripheral tissues in cancer patients.

Cancer patients have increased insulin resistance in skeletal muscles and probably also in the liver. The insulin production in response to a glucose challenge is decreased. This is associated with decreased glucose uptake in peripheral tissues and increased gluconeogenesis from amino acids, lactate, and glycerol. The correlation between the insulin response to a glucose challenge and the activities of glycolytic and oxidative rate-limiting enzymes in muscle tissue suggests a common denominator for these metabolic alterations. The most prominent feature in alteration of lipid metabolism is a reduction of body fat, probably dependent on increased lipolysis. The released fatty acids are oxidized outside the tumor mass. Species characteristics may be important for the degree of hyperlipidemia. Wasting of the skeletal muscle mass is caused by decreased protein synthesis and probably increased degradation. Anorexia can induce but not entirely explain this altered protein metabolism. Decreased physical activity may be another important factor for the depressed protein synthesis. Total parenteral nutrition (TPN) improves the muscle protein synthesis. The mechanism behind increased fractional degradation of muscle proteins in vitro is not clear, but it may be coupled to increased cathepsin D activity.

Animals↗

High oxygen pressure inhibits DNA synthesis in mitogen-activated lymphocytes.

Peripheral sheep lymphocytes, exposed to the mitogenic lectin phytohemagglutinin do not incorporate radiolabelled thymidine in cultures with a gas phase high in oxygen. Cells kept under nitrogen incorporate thymidine to the same extent or better than cells grown under air. The inhibition is proportional to the oxygen content of the gas phase. The inhibition is relieved if oxygen is replaced by air after some time but the onset of DNA synthesis is delayed correspondingly. It is suggested that oxygen may have a regulatory function on the onset of DNA synthesis.

Animals↗

Protein synthesis in liver tissue under the influence of a methylcholanthrene-induced sarcoma in mice.

Amino acids are incorporated at increased rates into hepatic proteins in tumor-bearing humans and animals. In this study, we hoped to elucidate whether this is an expression of increased hepatic protein synthesis or altered isotope dilution in the precursor pool(s). Liver tissue from sarcoma-bearing mice (MCG 101) showed increased specific activities of arginine and leucine in hepatic proteins after i.p. injection of these precursors. The specific radioactivity of leucine in the free amino acid incorporation rate into proteins was also found in incubated liver slices and in a cell-free system of incubated free and membrane-attached polysomes. The increased amino acid incorporation was the net result of increased as well as decreased relative turnover of various hepatic proteins. The hepatic content of RNA was increased, but hepatic DNA and protein content was unchanged in tumor-influenced livers. Increased amino acid incorporation into hepatic proteins in tumor-bearing animals and also probably in cancer patients is due to a net increased hepatic protein synthesis, probably not confined to acute-phase reactants only.

Animals↗

A comparative study of the influence of malignant tumor on host metabolism in mice and man: evaluation of an experimental model.

Metabolic alterations in skeletal muscles and liver tissue from cancer patients were compared with corresponding alterations in mice (C-57) with sarcoma (MCG-101). In tumor-bearing man and mice similar changes in enzyme activities and in protein turnover were found. Glycolytic and oxidative enzyme activities were decreased in skeletal muscle tissue. Tumor-associated increase in lysosomal enzyme activities was found in both species. Leucine was incorporated into skeletal muscle proteins at a lower rate and into hepatic proteins at a higher rate in both species with malignant tumor. In tumor-bearing mice ribosome profiles from skeletal muscle, heart muscle and liver showed a preponderance of slowly sedimenting units of polyribosomes suggesting that initiation of protein synthesis may be a rate limiting step. The metabolic host reactions in tumor-bearing mice were similar to those in cancer patients implying that experimental tumors are relevant to use for analysis of mechanisms behind the development of cancer cachexia in man.

Adult↗

Hydronephrosis. Assessment of late results after treatment of pelvi-ureteric junction obstruction.

Hydronephrosis is probably caused by a muscular anomaly at the pelvi-ureteric junction. A pyeloplasty technique involving the resection of this anomalous portion has been generally recommended. However, this study shows that procedures which preserve the anatomical continuity might also lead to excellent late results. The immediate postoperative complications were few and minor, and the low incidence of complications was partly the result of the splinting technique, which is therefore recommended. A scheme for evaluation of late results is suggested.

Adolescent↗

Trace element changes in serum and skeletal muscle compared to tumour tissue in sarcoma-bearing rats.

Cancer cachexia is characterized by wasting of the lean tissue and profound changes in the body composition of the tumour host. These changes are partly explained by an inefficient energy production but other factors may also be important, such as deficiency of essential nutritional components. In the present study the changes of trace elements in serum and skeletal muscle were compared to those in tumour tissue during tumour progression in sarcoma--bearing rats. Trace element analysis was performed directly on serum specimens and frozen sections from skeletal muscle and tumour tissue. The samples were analysed by energy dispersive X-ray fluorescence spectrometry (EDXRF) without any other pre-treatment such as homogenization and extraction. In skeletal muscle an increased content of zinc was found during tumour progression. The iron concentration was unchanged, but since muscle wasting is part of the cachexia this means that iron was transferred to other compartments. Thus the iron content of serum was doubled and tumour tissue had a high concentration of iron. Selenium was below detection limits in skeletal muscle but well detectable in tumour tissue and it increased during tumour growth. Rubidium and potassium content correlated in all tissues (R:0.98) as did bromine and sodium (R:0.98). Copper behaved differently from the other trace elements and showed large variability. This was also true when tissue copper was individually correlated to all other trace elements in the same tissue.

Animals↗