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Biomedical subjects

P Hahn

Publications and source records attributed to P Hahn.

At least 163 records · Page 9Linked to original sources

The "second messenger" system in brown adipose tissue of developing rats. Its molecular composition and mechanism of function.

Our studies of the hormonal receptor system and of the sequence of enzymatic events interconnecting the initial hormonal stimulus to the brown adipocyte with its final subcellular effect are summarized here. The hormone-mediated regulatory pathway consists of the adenyl cyclase and the protein kinase systems; the former is composed of the receptor and catalytic sites, the latter of regulatory and catalytic subunits. Emphasis is given currently to the diversity and characteristics of the individual components of the protein kinase system, since it seems to carry out the ultimate unifying mechanism involved in a variety of hormone-mediated functions, i.e. the phosphorylation of a protein molecule.

Adenylyl Cyclases↗

Effect of fasting on free and esterified carnitine levels in human serum and urine: correlation with serum levels of free fatty acids and beta-hydroxybutyrate.

Serum levels of free L-carnitine, acylcarnitines, creatinine, beta-hydroxybutyrate, free fatty acids, cholesterol, triglycerides, and glucose were determined in healthy volunteers during a 24-36-hr fast. The effect of oral administration of free L-carnitine (1 g/person) on these parameters was studied. Urinary excretion of carnitine and creatinine was monitored throughout. Serum and urine levels of free carnitine and its renal clearance decreased during the fast. However, the serum concentration and urinary excretion of acylcarnitines increased during the same interval. Following the ingestion of free L-carnitine, both serum and urinary levels of free L-carnitine rose. Within 6 hr of ingestion, 10% of the administered dose could be accounted for by urinary excretion. No significant effect on the other serum constituents under study was seen following the oral L-carnitine dose. A significant negative correlation was found between serum levels of free L-carnitine and beta-hydroxybutyrate and free fatty acids (r equal -0.567, p less than 0.001 and r equal -0.607, p less than 0.001, respectively) during the fast.

Acetylcarnitine↗

Regulation of phosphoenolpyruvate carboxykinase and fatty acid synthetase in brown fat of suckling rats.

Infant rats were injected with prednisolone (0.5-5 mg/100 g wt). This caused phosphoenolpyruvate carboxykinase (PEPCK) activity to rise in liver and to decrease in brown fat. Fatty acid synthetase (FAS) activity remained unchanged in liver but increased in brown fat. A single injection of prednisolone caused hepatic PEPCK activity to remain elevated for at least 7 days. Brown fat FAS also remained high for that period. However, brown fat PEPK activity returned to normal on the third day after the injection. A single injection of prednisolone or cortisone to 5-day-old rats caused a transient elevation of the blood level of insulin and a prolonged decrease in that of growth hormone. No effect on the level of glucagon was noted. Injections of insulin had effects similar to those of prednisolone, i.e. a rise in hepatic and a fall in brown fat PEPCK. Using antibodies prepared to hepatic PEPCK it was shown that the observed changes were due to changes in the rate of synthesis of the enzyme. Using actinomycin D indirect evidence was obtained that changes in FAS activity of brown fat were also due to changes in the synthetic rate.

Adipose Tissue, Brown↗

Acute skin reactions in postoperative breast cancer patients receiving radiotherapy plus adjuvant chemotherapy.

A group of 26 patients with operable carcinoma of the breast received postoperative radiotherapy plus adjuvant chemotherapy. Acute skin reactions were studied by clinical observation. There was a statistically significant difference (P less than .01) in the acute skin reactions in the chest wall area in those who received chemotherapy (81%) compared to the controls who received only radiotherapy (33%). Acute skin reactions began at the completion of postoperative radiotherapy and reached maximum severity 1-2 weeks later. They usually subsided after 4-6 weeks. No skin reactions were observed in the parasternal, supraclavicular fossa, or axillary regions. On the basis of these findings, postoperative radiotherapy combined with adjuvant chemotherapy is probably beneficial.

Breast Neoplasms↗

Control of blood cholesterol levels in suckling and weanling rats.

The high blood cholesterol and glucagon levels of suckling rats can be rapidly decreased within 24 hours by prematurely weaning rats to a high carbohydrate diet on day 18. The fall in the cholesterol level is much smaller if rats are starved for 24 hours. This decrease can partly be inhibited by injections of glucagon. The only factor so far found to decrease blood cholesterol levels in suckling rats was starvation. Insulin, which slightly but significantly, depressed the level in 40 day old rats, increased it in suckling ones, as does prednisolone. It is concluded that blood cholesterol levels are more easily manipulated in suckling rats than in older rats, and that this is probably related to a different hormonal balance.

Animals↗

Fructose-1,6-diphosphatase activity in brown adipose tissue of the developing rat.

An enzyme activity capable of converting fructose-1,6-diphosphate to fructose-6-phosphate was demonstrated to present in crude tissue extracts from brown adipose tissue of the rat. Mg2+ was essential for the expression of activity. EDTA (0.5 mM) increased the activity by 30%. Fructose-1,6-diphosphate in concentrations of 1 and 10 mM inhibits activity by 30% and 60% respectively. A 65% inhibition was observed in the presence of 0.2 micrometer 5' AMP. The activity of the enzyme was measured in rat brown adipose tissue at different stages of development. It rises sharply between day 2 and day 6 and continues to increase reaching a maximum between 6 and 11 days. Thereafter the activity gradually declines to values observed prenatally. The normal developmental rise in activity could be prevented by chemical sympathectomy on day 2. This procedure had no effect when carried out on day 9. There was a significant increase in enzyme activity after cold adaptation. The possible physiological significance of this enzyme in brown adipose tissue is discussed.

Adaptation, Physiological↗

Effect of 6-hydroxydopamine and alpha-methyltyrosine on brown adipose tissue of infant rats.

A single-dose administration of 6-hydroxydopamine (50 mg/kg body weight, sc) to infant rats resulted in an enlargement, higher fresh weight, markedly elevated lipid content, and higher total protein content of their interscapular and cervical brown adipose tissue. The protein kinase (EC 2.7.1.37) activation ratio in the tissue was decreased as was the phosphoenolpyruvate carboxykinase (EC 4.1.1.32) activity. Fatty acid synthetase, on the other hand, showed an increased activity. These changes commenced as soon as 24 h after the administration of the drug, were fully developed 2-4 days later, and persisted for at least 14 days. The results are in line with the assumption that 6-hydroxydopamine administration causes chemical sympathectomy of brown adipose tissue. This is further supported by the fact that treatment with alpha-methyltyrosine, which is known to competively inhibit norepinephrine systhesis, results in similar changes in brown fat of infant rats. Hence it seems that 6-hydroxydopamine administration offers a simple and inexpensive experimental model for studies of the role norepinephrine-mediated sympathetic nervous system in brown tissue function and development.

Adipose Tissue, Brown↗

Effect of premature weaning to different diets on the subsequent response to a dietary change.

Rats were weaned prematurely (day 18 postnatally) to a high-fat, high-carbohydrate or Purina Chow diet until aged 30 days. They were then fed the Purina Chow diet until aged 43 or 68 days. For a further 2 days they then received a high-fat diet. They were compared with rats weaned on day 30 to the Purina Chow diet. Adipose tissue of rats weaned prematurely to the high-carbohydrate diet or Purina Chow showed higher activities of phosphoenolpyruvate carboxykinase, malic enzyme and fatty acid synthetase than the same tissue from normally weaned rats or rats fed the high-fat diet from 18 to day 30. Prematurely weaned rats also have a higher level of blood cholesterol on day 45 after 2 days on the high-fat diet.

Adipose Tissue↗

Carnitine content of blood and amniotic fluid.

Free carnitine levels were determined in amniotic fluids between the 10th and 40th week of gestation. They were found to decrease significantly with gestational age. Blood levels of carnitine were lower in pregnant than in nonpregnant women. Levels were found to be higher in cord blood than in maternal blood and usually were higher in the umbilical artery than vein. Intra-arterial injection of L-carnitine into a pregnant ewe did not cause a rise in the fetal blood level of carnitine, which, in contrast to human fetal blood, contained less than half the level of carnitine in maternal blood.

Age Factors↗

[Psychosomatic aspects of cardiac and circulatory disorders (author's transl)].

Psychic stresses may cause cardiac reactions equal to those caused by physical strain. The intensity necessary for the psychic component to cause manifest clinical symptoms depends on the distinctness of the basic somatic cardiac disorder. Representing the group of functional cardiac and circulatory disorders the so-called phobic cardiac neurosis is discussed more in detail as well as the myocardial infarct as representatives of the group of coronary diseases. On the basis of tests (MMPI plus questionnaire) two groups may be differentiated. One group is characterized by pronounced dependance, sparing attitude, avoidance of situations and narrowing of environmental relations, the other by compensatory activity and physical engagement. The distinction is of relevance for therapeutic reasons and for reasons of somatic diagnosis. Among infarct patients we are presently trying to determine single psychic variables with respect to their importance as risk factors. Compulsiveness and rigidity or sociability and extraversion respectively appear to play a role.

Cardiovascular Diseases↗

Pyruvate dehydrogenase activity in liver and brown fat of the developing rat.

The total activity of pyruvate dehydrogenase (EC 1.2.4.1) and the fraction of the enzyme in the active form were assayed in brown fat and liver throughout the development of the rat. In brown adipose tissue, the total activity increased until the late suckling period. After weaning, a decrease was noted. The fraction of the enzyme in the active form did not increase until after 10 days of age, reached its highest level in the late suckling period and remained at this level after weaning. Pyruvate dehydrogenase in liver decreased in both total activity and percentage activity in the early neonatal period. Both parameters increased after this period, reaching their highest levels in the late suckling period. In both fetal liver and fetal brown fat, the total activity of pyruvate dehydrogenase was increased by in vitro incubation with insulin.

Adipose Tissue, Brown↗

Changes in tyrosine transaminase and phosphoenolpyruvate kinase activities during short term incubation of fetal liver.

Incubation of fetal rat liver homogenates at 37 degrees for 2-3 hr increased PEPK activity in the 100,000 X g supernatant 5-fold and TTA activity 10-fold. At the same time, activity in the 100,000 X g pellet decreaed and no change was observed in the whole homogenate. It is concluded that during incubation of fetal liver pieces or homogenates in vitro, a redistribution of enzymes occurs between cell particles and cell sap. It is suggested that release of enzyme into the cell sap may be the first stimulus for subsequent enzyme synthesis which occurs after birth.

Animals↗

Pulmonary radiation reaction in the treatment of carcinoma of the breast.

Chest roentgenograms were performed regularly before and a long time after radiotherapy in 157 patients with cancer of the breast. Radiation-induced parenchymal changes were demonstrated in 73 per cent of the patients and pleural effusions in about 10 percent. Total regression of the parenchymal changes were extremely rare, but a slight decrease in the volume of the affected lung was normal. The radiation-induced pleural effusion had no special characteristics, but, with one exception, it occurred simultaneously with radiation-induced parenchymal infiltrates, and it did not increase in quantity in any case.

Adult↗

Automated method for L-carnitine determination.

Because of renewed interest in a possible connection between carnitine, lipid disorders, and myopathy, an automated method of analysis is desirable. Deproteinization of serum by use of membrane filter cones and automated assay with a bichromatic analyzer (the ABA-100) substantially increases efficiency without sacrificing the specificity and accuracy of the original manual enzymatic method. The described procedure allows for analysis of 80 speciments a day and is thus suitable for screening of selected populations. Normal values found in blood sera of adults were in the range of 25.0-73.8 mu mol/liter and the method has sufficient sensitivity to accurately measure concentrations as small as 10 mu mol/liter.

Adult↗