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Biomedical subjects

K Hempel

Publications and source records attributed to K Hempel.

At least 109 records · Page 6Linked to original sources

[III. Continued education in surgery. A. Prospective studies, methods for determination of therapy results. Topics on and results of prospective studies in surgery].

Since the first clinical prospective trial of J. Lind in 1753, the controlled study has proved to be an essential instrument in clinical research. Possible topics include: pharmacologic prophylaxis of complications such as stress ulcer, thrombosis, etc., indications for operation, preoperative preparation, choice of surgical procedure, and techniques or postoperative treatment. Examples for each topic are given.

Clinical Trials as Topic↗

Increased histidine and histamine content in the brain of chronic uremic rats. Cause of enhanced cerebral cyclic adenosine monophosphate in uremia?

In rats with experimental chronic renal insufficiency (90% nephrectomy) the histidine content in brain was increased (+ 35%) in spite of normal plasma values and decreased concentrations in the striated muscle (-23%). The finding of a raised histidine level in the brain seems to be a uremia specific disorder, probably cuased by a local disturbance in histidine metabolism. In addition an increase of the histidine decarboxylation product histamine could be observed in the brain of rats with chronic renal insufficiency, as compared to pair-fed controls. This increase was directly related to the severity of azotemia. In the pathogenesis of the histamine alteration the increased histidine content in the brain of uremic rats must be considered, since the specific histidine decarboxylase is not saturated by the normal endogenous level of the amino acid precursor. Probably the increased histamine contributes to the raised cerebral cyclic AMP in the brain of uremic rats.

Animals↗

Monitoring of the specific radioactivity of S-adenosylmethionine in kidney in vivo.

The specific radioactivity of S-adenosylmethionine was followed in the cat kidney during the infusion of L-[Me-3H]methionine into the corresponding renal artery. For this purpose 14C-labelled 4-(2-aminoethyl)pyrocatechol([14C]dopamine) as methyl acceptor was injected locally every 15 min and the 3H and 14C activity of the methylation product homovanillic acid, isolated from urine, was measured. Approximately 5% of the 14C label is excreted during the first renal passage as [14C]homovanillic acid. The specific activity of S-adenosy[Me-3H]methionine in the kidney was calculated from the known specific radioactivity of [14C]dopamine injected and the measured radioactivity ratio, 3H: 14C, of homovanillic acid isolated from urine. The specific activity of S-adenosyl[Me-3H]methionine reaches a constant value in kidney about 30-60 min after the beginning of the L-[Me-3H]methionine infusion. This plateau value was 28% +/- 14% (n = 5) lower than the specific activity of L-[Me-3H]methionine in the venous blood from the corresponding kidney. The difference between the specific radioactivity of S-adenosyl[Me-3H]methionine in kidney and of free methionine in plasma is explained by the existence of a methionine source of minor specific activity in the kidney. The average life span of S-adenosylmethionine in the kidney is 19.5 +/- 8.7 min (n = 5).

Animals↗

Conformational changes induced by ionic strength and pH in two bovine myelin basic proteins.

The structures of two biologically different myelin proteins, A1 from the central nervous system and P2 from the peripheral nervous system, were investigated. Both proteins were isolated from nerve tissues. Conformational changes in the homogeneous proteins were examined in aqueous solutions by means of circular dichroism measurements. The secondary structures of both proteins proved to be very stable between pH 2.5 and pH 11.7. Unlike the P2 protein, the A1 protein is stable up to pH 13 without detectable conformational changes. The stereochemistry of the polypeptide chains of both proteins is markedly different in the presence of urea. While the value of theta222 for the A1 protein changes linearly with increasing urea concentration, a sigmoidal curve was obtained for the P2 protein. The observed differences in the dichroic properties of the basic myelin proteins A1 and P2 indicate the possibility of further structure - function correlations.

Animals↗

Synthesis of the glomerular basement membrane in the rat kidney. Autoradiographic studies with the light and electron microscope.

To study the origin and the formation of the glomerular basement membrane, autoradiographic investigations with 3H-proline and 3H-leucine have been performed in ultrathin with semithin sections of the glomeruli of 42 male rats. The results of this study indicate that, of the three cell types of the glomerulus, the epithelial cells (=podocytes) synthesize the proline-rich scleroproteins of the glomerular basement membrane. Our autoradiographic studies have yielded no evidence for participation of the endothelial or mesangial cells in the formation of the basement membrane. The mesangial cells appear to be responsible for the synthesis of the mesangial matrix only.

Animals↗

Inactivation and excretion of dopamine by the cat kidney in vivo.

14C-Dopamine at a dose between 0.16 and 400 nmol per kg body weight was injected locally into the renal artery and urinary excretion of the label was followed for a period of up to 75 min. During the first renal passage the injected kidney excreted 28.2+/-8.3% (n = 8) of the activity applied. As shown by column chromatography the 14C-activity in urine was mainly present as 3,4-dihydroxyphenyl acetic acid (40%), homovanillic acid (15%) and dopamine (app. 20%). Excretion rate and the pattern of dopamine metabolites in urine was independent of the administered dose. Thus, the excretion of dopamine by the cat kidney is linked to an inactivation by the kidney enzymes MAO and COMT. From the literature it is known that in dog and chicken kidney catecholamines are not metabolized to such a large extent during renal excretion.

Animals↗

[Ureteral lesions after abdomino-perineal resection of the rectum].

Three ureter lesions in abdominoperineal rectum amputations are described. The surgical literature on this subject is discussed. Particularly dangerous points in the procedure of abdominoperineal rectum amputation concerning injuries of the ureter are accentuated. Possibilities of avoiding and recognizing early ureter injuries are indicated. More attention should be given to intraoperative lesions of the ureter.

Abdomen↗

[Raised cAMP content of striated muscle in experimental chronic renal failure (author's transl)].

3', 5'-Adenosine monophosphate (cAMP) levels were determined in skeletal and heart muscle tissue of rats in chronic renal failure. Compared to normal animals no alteration in cAMP concentration was observed in heart muscle, whereas the cAMP levels in skeletal muscle were increased by 34%. This cAMP rise may be caused by the elevated plasma catecholamines, glucagon or parathyroid hormone levels in uraemia. The results suggest that the increased cAMP levels in skeletal muscle of rats in chronic renal failure contribute to the raised cAMP levels in the plasma.

Animals↗

[Increased cAMP concentration in parotid secretion in arterial hypertension: relationship to plasma-renin activity (author's transl)].

Hypertensives with normal and increased plasma-renin activity have an increased salivary excretion of cyclic adenosine monophosphate (cAMP) such as can be obtained in normal persons by stimulation of beta-adrenergic fibres. Propanolol, as a beta-receptor blocker, reduces such increased cAMP levels in hypertensives to minimal levels. The results suggest that beta-receptors are stimulated in hypertensives with normal or increased renin activity.

Cyclic AMP↗

Kinetics of histone methylation in vivo and its relation to the cell cycle in Ehrlich ascites tumor cells.

The appearance of methylated lysines in newly synthesized histones from Ehrlich ascites tumor cells was measured during one generation time. Newly synthesized histones were pulse-labeled in vivo by L-[3H]lysine, and the time course of the uptake of label into monomethyl, dimethyl and trimethyllysine from gel-electrophoretically isolated histones F2a1 (H4) and F3 (H3) was followed. Methylation starts immediately after histone biosynthesis. It proceeds, however, more slowly than histone synthesis. Both the rate of methylation and the mechanism of methylation in F3 and F2a1 histones differ. F3 methylation can be described by a first-order reaction, i.e. the reaction rate depends only on the concentration of free methylation sites available. Rate constants of approximately 0.21 h-1 were found for all three methylation steps. Methylation in the F2a1 histone proceeds more slowly than in F3. The dimethylation step in this fraction can be described by a zero-order reaction with a rate constant which is the reciprocal of the duration of the DNA synthesis phase. Alternatively this step could be correlated with the transition of the cells from the S phase into the G2 phase. By the end of one generation time all methylation sites in all F2a1 and F3 molecules are occupied by methyl groups at a ratio of about 1:3:1 for monomethyl, dimethyl and trimethyllysine in the F3 histone. In the F2a1 molecule the methyllysines consist mainly of dimethyllysine.

Amino Acids↗

Diagnostic meaning of the urinary output of Nepsilon-methylated lysines. Investigation of healthy individuals and patients with malignant diseases, myopathies or renal failure.

In the urine of 36 healthy persons the excretion of the three Nepsilon-methylated lysines and some other basic amino acids was determined. The following average values, related to 1 g creatinine, were found: Lys(Me) 16.2 mumol, Lys(Me2) 31.2 mumol, Lys(Me3) 40.5 mumol. The 24-hour excretion in 6 adults related to 1 kg body weight, had the following average values: Lys(Me) 0.37 mumol, Lys(Me2) 0.88 mumol, Lys(Me3) 0.92 mumol. In patients with degenerative or inflammatory myopathies (6 cases) as well as with generalized tumors (7 cases) urinary output of methyllysines was not significantly altered. In a patient with extremely impaired renal function, it was found that the plasma level and the excretion pattern of the methylated lysines were unequivocally altered. Metabolic stability and renal excretion of 3H-labelled l-Lys(Me3) were investigated in man. During a 24 hour period 65 per cent of Lys(Me3) was excreted into the urine unmetabolized after intravenous injection but not more than 20 per cent after oral administration.

Adolescent↗

Differences in the incorporation of L- and DL-Amino acids into renal tubular cells. An autoradiographic study.

The cytoplasmic uptake of 3H-L-leucine and 3H-L-proline by hepatocytes and cells of the proximal and distal convoluted and of the collecting tubules of the kidney was compared with that of 3H-DL-leucine and 3H-DL-proline in an autoradiographic study. 34 male white Sprague-Dawley rats were killed 1, 2, 6, and 24 hours after the intraperitoneal injection of these amino acids. The rate of incorporation of 3H-L-leucine in the liver and in the renal tubules, as judged by the number of silver grains counted, was about twice that of 3H-L-proline. In the tubules of the kidney the intensity of labelling progressively declined from the proximal convoluted to the collecting tubules. When the two 3H-DL-amino acids were used, almost identical rates of incorporation were found in the liver as well as in the kidney. The only exception was the pars recta of the proximal tubule: Here there could be found an unusually high uptake of 3H-DL-proline. The values were not only higher than those found for the uptake of 3DL-leucine in this particular segment, but they also surpassed those due to 3H-DL-proline and 3DL-leucine in the other parts of the renal tubules, as well as in the liver. The conspicuously high labelling seen in the pars recta after the injection of 3H-DL-proline suggests that there is present in the cells of this segment a d-amino acid oxidase, which may be relatively specific for D-proline. The possibility is considered that this enzyme may participate in a detoxifying function of the pars recta.

Amino Acids↗