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Biomedical subjects

K Schmid

Publications and source records attributed to K Schmid.

At least 109 records · Page 6Linked to original sources
PubMed1989

Spectral composition of synchronized discharge of phrenic nerve activity in the rabbit and effects of pulmonary afferents.

In anaesthetized rabbits synchronization of efferent phrenic nerve discharge activity (PNA) was investigated by spectrum analysis. During hypercapnia (6-8% end-tidal CO2) in almost all animals the spectrum analysis of PNA during inspiration revealed a bimodal distribution. A broad peak was present at 45.9 +/- 7.7 Hz (MFO peak) whereas a usually well-defined peak with smaller band width was located at 100.3 +/- 17.1 Hz (HFO peak). Increase of hypercapnia promoted the peak amplitude of HFO but had no consistent effect on the amplitude of MFO. Synchronization in the HFO band gradually increased with the progress of inspiration but declined during the last third of inspiration. HFO could be demonstrated to be also present in postinspiratory activity. The amplitude of MFO slowly increased during inspiration becoming strongest at the end of inspiration. The effect of afferent inputs from pulmonary stretch receptors on synchronization of PNA was found to be very weak. Neither withholding inflation during inspiration nor bilateral vagotomy produced substantial changes of MFO and HFO. Tracheal occlusions, however, during inspiration resulted in a slight increase of the power of MFO and HFO, which mainly was due to an overall increase of power. Augmented breaths resulted in a strong shift of the HFO peak to higher frequencies which was accompanied by a dramatic increase of the peak amplitude and a decrease of the peak band width. The presumptive role of the different types of phrenic motoneurons conveying HFO is addressed.

Animals↗
PubMed1989

Nucleotide sequences and operon structure of plasmid-borne genes mediating uptake and utilization of raffinose in Escherichia coli.

The plasmid-borne raf operon encodes functions required for inducible uptake and utilization of raffinose by Escherichia coli. Raf functions include active transport (Raf permease), alpha-galactosidase, and sucrose hydrolase, which are negatively controlled by the Raf repressor. We have defined the order and extent of the three structural genes, rafA, rafB, and rafD; these are contained in a 5,284-base-pair nucleotide sequence. By comparisons of derived primary structures with known subunit molecular weights and an N-terminal peptide sequence, rafA was assigned to alpha-galactosidase (708 amino acids), rafB was assigned to Raf permease (425 amino acids), and rafD was assigned to sucrose hydrolase (476 amino acids). Transcription was shown to initiate 13 nucleotides upstream of rafA; a putative promoter, a ribosome-binding site, and a transcription termination signal were identified. Striking similarities between Raf permease and lacY-encoded lactose permease, revealed by high sequence conservation (76%), overlapping substrate specificities, and similar transport kinetics, suggest a common origin of these transport systems. alpha-Galactosidase and sucrose hydrolase are not related to host enzymes but have their counterparts in other species. We propose a modular origin of the raf operon and discuss selective forces that favored the given gene organization also found in the E. coli lac operon.

Amino Acid Sequence↗
PubMed1989

Unusually high concentrations of Zn alpha 2-glycoprotein and the lack of alpha 2HS-glycoprotein in human ejaculates.

Ejaculates of 132 nonvasectomized and 129 vasectomized men were assayed for their Zn alpha 2- and alpha 2HS-glycoprotein contents by radial immunodiffusion. The respective mean concentrations of Zn alpha 2-glycoprotein were 319 and 309 mg/L, respectively, but these fluids were devoid of alpha 2HS-glycoprotein. In comparison, the concentration of these two proteins in serum of normal men were 62 and 617 mg/L for Zn alpha 2- and alpha 2HS-glycoprotein, respectively. Because albumin in the ejaculates is 100-fold less concentrated than in serum, the fivefold increase in the concentration of Zn alpha 2-glycoprotein of the ejaculates represents about a 500-fold enrichment of this protein in the ejaculates over the concentration expected by comparison with albumin.

Adult↗
PubMed1989

Disposition of [14C]-benazepril hydrochloride in rat, dog and baboon. Absorption, distribution, kinetics, biotransformation and excretion.

The compound 3-[(1-ethoxycarbonyl-3-phenyl-(1S)-propyl)-amino]-2,3,4,5- tetrahydro-2-oxo-1-(3S)-benzazepine-1-acetic acid hydrochloride (benazepril.HCl, CGS 14 824 A) is an ethyl ester prodrug of the angiotensin converting enzyme (ACE) inhibitor benazeprilat (CGS 14 831). The disposition of both compounds was studied in rat, dog and baboon after peroral and intravenous dosing of 14C-labelled preparations (2.5-3 mg/kg). Perorally dosed benazeprilat was poorly absorbed in rats, whereas benazepril.HCl was well absorbed in all species. Onset of absorption of benazepril.HCl was fast. Plasma concentrations of radioactivity indicated a prolonged absorption process. Upon intravenous benazepril.HCl, plasma levels declined rapidly in all species but showed a slow terminal elimination phase. Distribution to all organs and tissues occurred rapidly and was typical for an acid compound. Passage of the blood-brain barrier and of the placenta occurred to a minimal extent. No accumulation was observed after repeated dose. Radioactivity was rapidly and completely eliminated; biliary excretion was important. In the rat, benazepril was completely hydrolysed by first pass metabolism to the pharmacologically active benazeprilat. In dog and baboon hydrolysis was incomplete and additional hydrophilic metabolites were formed also.

Animals↗
PubMed1989

[The use of fenbendazole for controlling helminths in small zoo ruminants].

By means of coproscopical examination the anthelmintic efficacy of 5.0 mg fenbendazole/kg body weight and 0.714 mg/kg body weight, administered for seven consecutive days, was determined in three series of trials on small ruminants in the zoological gardens of Munich. Both doses proved to be highly effective against trichostrongylids; the egg output was reduced to an average of 100% and 80-100%, respectively. Despite of a partly lower efficiency after the multiple administration of a low level doses (7 x 0.714 mg fenbendazole/kg body weight) this is a sufficient and economical treatment for the control of the infestation with endoparasites in the - in this respect - difficult housing systems of zoological gardens.

Animals↗
PubMed1988

The carbohydrate composition of human serum amyloid P component.

The carbohydrate moiety of human serum amyloid P component was analyzed and found to consist of equal amounts of galactose and mannose (total 4.0%), of glucosamine and galactosamine in a ratio of 7:1 (total 2.7%) and sialic acid (3.9%). It should be noted that this is the first report on the separate quantification of the neutral hexoses and the demonstration of the presence of galactosamine. The contents of glucosamine and galactosamine suggest that this protein possesses both an N- and an O-glycan.

Carbohydrates↗
PubMed1988

The N- and O-linked carbohydrate chains of human, bovine and porcine plasminogen. Species specificity in relation to sialylation and fucosylation patterns.

The structures of the N- and O-glycans of human, bovine and porcine plasminogen were determined by 500-MHz 1H-NMR spectroscopy. The N-glycans of all three species proved to be of the N-acetyllactosamine type differing from one another with respect to the sialylation and fucosylation patterns. In the N-glycan of human plasminogen the two antennae are sialylated with N-acetylneuraminic acid (NeuAc), whereas in the bovine counterpart both branches carry significant amounts of N-glycolylneuraminic acid (NeuGc). In porcine plasminogen the sialic acid is mainly NeuAc; the Man alpha 1----6 branch, however, is only partially sialylated. In addition, the porcine N-glycan is fucosylated to about 80% in alpha 1----6 linkage to the GlcNAc-1 residue. The O-glycans of the three species possess an identical Gal beta 1----3GalNAc core which is alpha 2----3 sialylated with NeuAc at Gal. The disialylated form, which is also present in all three species, has an additional NeuAc residue in alpha 2----6 linkage to GalNAc. Mono- and disialylated forms occur in different molar ratios in the different plasminogens: 80:20 in human, 70:30 in bovine and 50:50 in porcine. This study on the carbohydrate moiety of these three plasminogens reveals species specificity in terms of various types of microheterogeneities.

Animals↗
PubMed1988

Determination of the angiotensin converting enzyme inhibitor benazeprilat in plasma and urine by an enzymic method.

An enzyme inhibition assay for the angiotensin-converting enzyme (ACE) inhibitor benazeprilat is described. Plasma and urine samples were diluted and endogenous ACE was inactivated by heating. After incubation of the plasma samples with hippuryl-histidyl-leucine as substrate and blank plasma as the source of ACE, released hippuric acid was measured by high-performance liquid chromatography. Urine samples were incubated with [3H] hippuryl-glycyl-glycine and with rabbit lung extract as the source of ACE. Released [3H] hippuric acid was quantified by liquid scintillation counting. Drug standards for the standard curve were prepared in the biological matrix. A cross-check with a gas chromatographic-mass spectrometric method showed good agreement, demonstrating that this enzymic method is suitable for assessing drug bioavailability and pharmacokinetics.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

In vitro nerve-growth-promoting activity of human plasma alpha 1-acid glycoprotein.

Human plasma alpha 1-acid glycoprotein or orosomucoid (OR), and its derivatives, prepared by sequential enzymatic cleavage of the carbohydrate units, were tested for their nerve-growth-promoting activities with explants of whole dorsal root ganglia from chick embryos. The results showed that the OR derivatives with terminal galactose, N-acetylglucosamine, or mannose have marked neurite-promoting activities. These preparations at a concentration of 100 micrograms/ml are equivalent to 5% fetal bovine serum (protein concentration 3,000 micrograms/ml) in their ability to elicit extensive neurite outgrowth and collateral branching. The asialo-OR, or ASOR, is the most potent form: its activity is estimated to be 20 times higher than that of transferrin and 100 times over that of fibronectin; it is approximately 1/1,500 that of NGF. The neurite-promoting activity of OR is independent of the non-neuronal cells and their products and can be blocked by a specific antiserum against OR. The mode of action of OR on the in vitro nerve growth is discussed and the pathophysiological significance of this plasma glycoprotein is considered in light of data from recent clinical and pathological studies.

Animals↗
PubMed1988

Influence of rubrospinal tract and the adjacent mesencephalic reticular formation on the activity of medullary respiratory neurons and the phrenic nerve discharge in the rabbit.

Suprapontine brain sites acting on the central respiratory system have been demonstrated to give rise to inspiratory as well as expiratory facilitatory effects. In the present study the inspiratory inhibitory effect which has been reported in the cat to be elicited consistently by electrical stimulation of the rubrospinal tract and the adjacent mesencephalic reticular formation was examined in the urethane-anaesthetized rabbit. Stimulation of these sites with single electrical shocks of moderate intensity induced a short latency (onset after 3.0 ms) transient (duration: 29 ms) inhibition of the phrenic nerve activity (PHR). Short volleys of stimuli applied in mid- to late-inspiration led to a premature off-switch of inspiration. The extracellularly recorded discharge activity of the different types of medullary respiration-related units (RRU) reflected these alterations, accordingly. Axonal connections of RRU with mesencephalic structures were evaluated. Examination of orthodromic responses of medullary RRU to stimulation of this pathway revealed that most bulbospinal inspiratory neurons (10 out of 13) were paucisynaptically inhibited after short latency (at least 1.2 ms). The conduction time from bulbospinal inspiratory neurons to the recording site of PHR was 1.6 ms. Thus, a disynaptic pathway--including bulbospinal inspiratory neurons--is suggested inducing inspiratory inhibition 3.0 ms after single shock midbrain stimulation. This inhibition results in disfacilitation of phrenic motoneurons. The fact that extensive electrolytic lesions of the pneumotaxic center in rostral pons did not abolish the observed inspiratory inhibitions excludes these structures from being involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

A method for the quantitative analysis of nerve growth in vitro.

A method is described for the quantitative analysis of the nerve-growth-promoting activity of biological molecules in tissue culture. The criteria used for the evaluation of this activity is based on the neurite length as well as the total number of neurites produced by the explant of whole dorsal root ganglia from 12-d-old chick embryos. A nerve growth index (NGI) is given to each ganglion during each of a 5-d culture period. The NGI is defined as the product of average neurite length in millimeters and the total number of neurites. We report that with increasing concentrations of fetal bovine serum, there was a proportional increase in NGI due to increased neurite density while the neurite length was not greatly affected. The NGI of several proteins with known nerve growth promoting activity, namely nerve growth factor, insulin, transferrin, and fibronectin were investigated for their activity and compared with that of fetal bovine serum.

Animals↗
PubMed1988

Glycosaminoglycan content in neonatal rat aortic smooth muscle cell cultures.

In the present study the biosynthesis of glycosaminoglycans (GAGs) by neonatal rat aortic smooth muscle cells in culture was studied. Heparan sulfate (HS) was the predominant GAG of the cell layer accounting for 32-49% of the total GAGs depending on the time in culture. The presence of low sulfated chondroitin sulfate (LSC) in aortic smooth muscle cell cultures is reported here for the first time. The effect of ascorbate on the synthesis and accumulation of these macromolecules resulted in a relative increase of C4S and DS in the cell layer. In contrast, the distribution of the GAGs which were secreted into the medium was not significantly effected by the addition of ascorbate. While HS was always found to be a minor component, the other GAGs were present in about equal concentrations. The total GAG accumulation in the medium was much greater (91-97%) than that of the cell layer (3-9%) indicating that the cells are synthesizing relatively large amounts of GAGs, although incorporation of these macromolecules into the extracellular matrix was consistently low.

Animals↗
PubMed1988

Plasmid-mediated sucrose metabolism in Escherichia coli K12: mapping of the scr genes of pUR400.

The scr genes located on plasmid pUR400 and responsible for sucrose (Scr) metabolism of Escherichia coli K12 and other enteric bacteria have been cloned on a 9.3 kb DNA fragment. The different genes were mapped by transposon insertion mutagenesis, by restriction endonuclease and deletion mapping, and the corresponding gene products were identified. Besides the known structural genes scrA, coding for an EnzymeII(Scr) (45 kD) of the phosphoenolypyruvate-dependent phosphotransferase system (PTS), and scrB, coding for a sucrose 6-phosphate hydrolase (invertase) (55 kD), two new structural genes were discovered. Gene scrK apparently codes for an intracellular and ATP-dependent fructokinase (39 kD), while scrY seems to code for a sucrose porin (58 kD) in the outer cell membrane. No genes for an Enzyme III(Scr) of the PTS or for (a) glycosyltransferase(s) were detected. The four genes form an scr operon (gene order, scrK scrY scrA scrB, transcription from K to B), regulated by a repressor (gene scrR, 37 kD) and inducible by sucrose, fructose and fructose-containing oligosaccharides.

DNA Restriction Enzymes↗
PubMed1988

Human serum alpha 2HS-glycoprotein modulates in vitro bone resorption.

We previously isolated a family of bone-resorbing proteins from human cancer ascites fluid and established that the three purified bone-resorbing proteins were chemically and immunochemically related to each other and to alpha-2HS glycoprotein (alpha 2HS). After this finding we purified the normal human serum counterpart of these ascites proteins and studied its effects on bone resorption. The bone-resorbing properties of normal human serum alpha 2HS were examined in vitro over a wide dose range. This normal human serum glycoprotein had a biphasic effect on 45Ca2+ release from bone. More specifically, this protein stimulated bone resorption at the lower concentrations tested, with a maximum effect [treated over control ratio of 2.5 +/- 0.30 (+/- SE); P less than 0.01] at 40 micrograms/mL. In contrast, at doses above 40 micrograms/mL, a sharp decline in calcium mobilization occurred, with a return to baseline occurring above 80 micrograms/mL. These results suggest that serum alpha 2HS may participate in the regulation of bone metabolism in vivo.

Adult↗
PubMed1987

The structures of N- and O-glycosidic carbohydrate chains of a chondroitin sulfate proteoglycan isolated from the media of the human aorta.

A large Mr chondroitin sulfate proteoglycan was extracted from the media of human aorta under dissociative conditions and purified by density-gradient centrifugation, ion-exchange chromatography, and gel filtration chromatography. Removal of a contaminating dermatan sulfate proteoglycan was accomplished by reduction, alkylation and rechromatography on the gel filtration column. After chondroitinase ABC treatment, the proteoglycan core was separated from a residual heparan sulfate proteoglycan by a third gel filtration chromatography step. As assessed by radioimmunoassay, the isolated proteoglycan core was free of link protein, but possessed epitopes that were recognized by antisera against the hyaluronic acid binding region of bovine cartilage proteoglycan as well as those that were weakly recognized by anti-keratan sulfate antisera. Following beta-elimination of the protein core, the liberated low Mr oligosaccharides were partially resolved by Sephadex G-50 chromatography, and their primary structure was determined by 500-MHz1H NMR spectroscopy in combination with compositional sugar analysis. The N-glycosidic carbohydrate chains, which were obtained as glycopeptides, were all biantennary glycans containing NeuAc and Fuc; microheterogeneity in the NeuAc----Gal linkage was detected in one of the branches. The N-glycosidic glycans have the following overall structure: (Formula: see text). The majority of the O-glycosidic carbohydrate chains bound to the protein core were found to be of the mucin type. They were obtained as glycopeptides and oligosaccharide alditols, and possessed the following structures: NeuAc alpha(2----3)Gal beta(1----3)GalNAc-ol, [NeuAc alpha(2----3)Gal beta(1----3)[NeuAc alpha(2----6)]GalNAc-ol, and NeuAc alpha-(2----3) Gal beta(1----3)[NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)] GalNAc-ol. The remainder of the O-glycosidic carbohydrate chains bound to the isolated proteoglycan were the hexasaccharide link regions of the chondroitin sulfate chains that remained after chondroitinase ABC treatment of the native molecule. These latter glycans, which were obtained as oligosaccharide alditols, had the following structure (with GalNAc free of sulfate or containing sulfate bound at either C-4 or C-6): delta 4,5GlcUA beta(1----3)GalNAc beta(1----4)GlcUA beta(1----3)Gal beta(1----3)Gal beta(1----4)Xyl-ol.

Amino Acids↗