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Biomedical subjects

A Schwab

Publications and source records attributed to A Schwab.

70 records · Page 4Linked to original sources

[Cancer of the large intestine--a sequela of ureterosigmoidostomy].

Carcinoma or polyps of the colon as a late complication of ureterosigmoidostomia (USS) have been reported with increasing frequency. Three patients are presented, two of them developed a signet-ring cell carcinoma after USS; one patient showed, 6 years after rediversion of the ureter, a carcinoma at the anastomotic site. Changes in the secretion patterns of sialo- and sulphomucines of the tumor and mucosa are histochemically demonstrated and, together with an appraisal of etiologic factors, discussed. We suggest a careful follow-up of patients with USS, particularly of those performed many years ago.

Adenocarcinoma, Mucinous↗

Relationship between luminal Na+/H+ exchange and luminal K+ conductance in diluting segment of frog kidney.

Experiments were performed in the isolated perfused kidney of K+ adapted Rana pipiens to investigate the relationship between luminal K+ conductance and H+ transport in cells of the diluting segment. Inhibition of luminal Na+/H+ exchange by amiloride or by omission of luminal Na+ blocked luminal K+ conductance. Acidification of the kidney perfusate by elevation of pCO2 also reduced luminal K+ conductance. This effect could be prevented by furosemide. Since the steepest transcellular Na+ potential difference, directed from the lumen into the cell, is found when luminal Na+/Cl-/K+ cotransport is inhibited by furosemide, we conclude that luminal Na+/H+ exchange is most efficient at these conditions and thus could attenuate intracellular acidification.

Amiloride↗

Angiotensin-converting enzyme inhibitors. New orally active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives.

A variety of N-substituted (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives was synthesized and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) was examined in vitro and in vivo. The acylthio derivatives prepared are assumed to act as prodrugs since they are much less active than the corresponding free SH compounds in vitro and can be expected to act in vivo only after conversion to the free sulfhydryl compounds. A number of these compounds are potent ACE inhibitors that lowered blood pressure in Na-deficient, conscious spontaneously hypertensive rats (SHR), a high renin model. One of the most active members of the series was (S)-N-cyclopentyl-N-[3-[(2,2-dimethyl-1-oxopropyl)thio]-2-methyl-1 -oxopropyl]glycine (REV 3659-(S), pivopril). Structure-activity relationships are discussed.

Administration, Oral↗

Angiotensin converting enzyme inhibitors. (Mercaptoaroyl)amino acids.

A series of (mercaptoaroyl)amino acids and related compounds was synthesized and tested for ability to inhibit angiotensin converting enzyme (ACE). The most active compound was N-(3-chloro-2-mercaptobenzoyl)-N-cyclopentylglycine, having an in vitro I50 = 0.28 microM. Substitution of the aromatic 3-position by small polar groups enhanced ACE inhibitory activity, whereas bulky groups diminished it. Alteration of the beta relationship between the mercaptan and amide carbonyl or masking of the thiol by acylation reduced activity. Replacement of the thiol by nitro, hydroxy, or carboxy gave compounds lacking ACE inhibitory activity.

Amino Acids↗

Inhibition of angiotensin-converting enzyme by dipeptide analogs.

Several dipeptide analogs containing an acyclic teritary amide group are effective angiotensin-converting enzyme (ACE) inhibitors with I50 values comparable to those of the best natural dipeptide inhibitors (e.g. Val-Trp). The most potent inhibitors studied feature a p-tolyl or norbornyl substituent on the amide nitrogen atom and a methyl or butylamino substituent on the carbon atom alpha to the amide group. REV 5277-R, alanyl-N-exo-norbornyl-glycine, is a competitive inhibitor of rabbit lung ACE with a Ki value of 9 microM.

Angiotensin-Converting Enzyme Inhibitors↗

Effect of neurotensin on exocrine pancreatic secretion in dogs.

The effects of various doses of synthetic neurotensin on exocrine pancreatic secretion were investigated in dogs prepared with pancreatic fistulae. Increasing doses of neurotensin infused intravenously caused a dose-dependent stimulation of exocrine pancreatic secretion. Plasma neurotensin levels determined with a radioimmunoassay kit for neurotensin were significantly correlated to the amount of neurotensin infused. Significant stimulation of exocrine pancreatic secretion was observed when 2.5 pmol kg-1 min-1 neurotensin were infused. This dose resulted in neurotensin plasma levels comparable to those observed after a meal. Combined infusions of neurotensin and the cholecystokinin analogue cerulein had synergistic effects on pancreatic bicarbonate output and raised the HCO-3:protein ratio. These observations suggest that neurotensin may play a role in the early phase of postprandial stimulation of exocrine pancreatic function.

Animals↗

Carbon-14 tracer studies in rat-liver perfusion experiments under conditions of gluconeogenesis from lactate and pyruvate.

The intracellular events in the metabolic pathway of gluconeogenesis from lactate and pyruvate in liver tissue were assumed to be understood. Nevertheless the results of several 14C-tracer experiments gave rise to the postulation of still unknown intracellular interactions under this condition. We have tried to contribute to the solution of this problem by using different 14C labeled tracers such as [1-14C]lactate or pyruvate and [2-14C]lactate or pyruvate, [14C]bicarbonate and [1-14C]octanoate in perfusion experiments with livers from rats under conditions of gluconeogenesis from lactate and pyruvate. The 14C labeling patterns of intracellular metabolites as malate, citrate, phosphoenolpyruvate, phosphoglycerate and newly synthesized glucose were analysed under different conditions. A comparison with values calculated by using metabolic models, based on the generally accepted concepts of intracellular interactions, showed some fundamental discrepancies, which justify the postulation of still unknown intracellular interactions in the pathway of gluconeogenesis from lactate and pyruvate.

Acetoacetates↗

Extracellular detection of K+ release during migration of transformed Madin-Darby canine kidney cells.

Madin Darby canine kidney cells transformed by alkaline stress (MDCK-F cells) constitutively migrate at a rate of about 1 microm.min-1. Migration depends on the intermittent activity of a Ca2+-stimulated, 53-pS K+ channel (KCa channel) that is inhibitable by charybdotoxin. In the present study we examined whether this intermittent KCa channel activity results in a significant K+ loss across the plasma membrane. K+ efflux from MDCK-F cells should result in a transient increase of extracellular K+ ([K+]e) in the close vicinity of a migrating cell. However, due to the rapid diffusion of K+ ions into the virtually infinite extracellular space, such a transient increase in [K+]e was too small to be detected by conventional K+-selective electrodes. Therefore, we developed a "shielded ion-sensitive microelectrode" (SIM) that limited diffusion to a small compartment, formed by a shielding pipette which surrounded the tip of the K+-sensitive microelectrode. The SIM improved the signal to noise ratio by a factor of at least three, thus transient increases of [K+]e in the vicinity of MDCK-F cells became detectable. They occurred at a rate of 1.3 min-1. The cell releases 40 fmol K+ during each burst of intermittent KCa channel activity, which corresponds to about 15% of the total cellular K+ content. Since transmembrane K+ loss must be accompanied by anion loss and therefore leads to a decrease of cell volume, these findings support the hypothesis that intermittent volume changes are a prerequisite for the migration of MDCK-F cells.

Animals↗

Role of the Na/H exchanger NHE1 in cell migration.

Cell migration plays a basic role in many physiological and pathophysiological processes such as embryogenesis, immune defence, wound healing or metastasis. The activity of the ubiquitously expressed NHE1 isoform of the plasma membrane Na+/H+ exchanger is one of the requirements for directed locomotion of migrating cells and also contributes to cell adhesion. The mechanisms by which NHE1 is involved in cell migration are multiple. NHE1 contributes to cell migration by affecting the cell volume, by regulating the intracellular pH and thereby the assembly and activity of cytoskeletal elements, by anchoring the cytoskeleton to the plasma membrane, by signalling, by regulating gene expression and by controlling cell adhesion. The present article gives a review of the different ways in which NHE1 is involved in and contributes to cell migration. These different mechanisms complement one another forming an intricate, integrative process.

Animals↗

[Antistreptolysin-o latex test. A simple screening method for the determination of antistreptolysin-o antibodies].

Experiences with a rapid latex slide test to distinguish elevated fron normal antistreptolysin-O titers are reported. A series of 1000 randomly selected sera were tested in parallel with the ASO latex test and the classical antistreptolysin-O titration test. All sera with an ASO titer of more than 200 I.U. produced a positive agglutination with the ASO latex test. No false negative results were recorded. 6,2% of the sera with a positive ASO latex test exhibited less than 200 I.U. in the titration test. A further advantage of the ASO latex test, apart from its easy practicability, is that it is not inhibited by serum lipids like the hemolytic titration test. The dextransulphate precipitation method combined with the ASO titration showed no advantaged when compared with the ASO latex test combined with the ASO titration without dextransulphate. When patients in our series with ASO TITERS OF 500 AND MORE I.U. were considered in relation to their clinical diagnosis it as found that infections with beta-hemolytic streptococci would not be overlooked, when the ASO latex test is used as a screening procedure. The ASO latex test therefore all s a considerable reduction of personnel and working time. It is however, essential that industry should keep the quality of latex reagents strictly standardized.

Antibodies↗