Biomedical subjects

K Schmid

Publications and source records attributed to K Schmid.

At least 19 recordsLinked to original sources

PubMed1992

Structure of the N- and O-glycans of the A-chain of human plasma alpha 2HS-glycoprotein as deduced from the chemical compositions of the derivatives prepared by stepwise degradation with exoglycosidases.

The structure of the glycans of the A-chain of human plasma alpha 2HS-glycoprotein was established from the chemical compositions of its derivatives prepared by sequential enzymatic degradation of the carbohydrate moiety, from the determination of the kind and amount of the monosaccharides liberated after each step of the enzymatic digestion, and from the distinct specificity of the highly purified exoglycosidases. The exoglycosidases were three sialidases (Vibrio cholerae, fowl plague virus, and Arthrobacter ureafaciens), two beta-galactosidases (Streptococcus pneumoniae and bovine testis), one alpha-N-acetylgalactosaminidase, one beta-N-acetylglucosaminidase, and one alpha-mannosidase. Utilizing sialidases with different cleavage specificities, the number of alpha 2-3- and alpha 2-6-linked sialic acid residues could be separately determined. As to the beta-galactosidases, the enzyme isolated from S. pneumoniae cleaves only beta 1-4-linked galactose residues, whereas the bovine testes enzyme acts on both the beta 1-4- and beta 1-3-linked galactose residues. Jack bean beta-N-acetylglucosaminidase cleaves beta 1-2, beta 1-4, and beta 1-6 GlcNAc with higher activity for the beta 1-2. Jack bean alpha-mannosidase cleaves alpha 1-2, alpha 1-6, and alpha 1-3 Man with greater activity for alpha 1-2 and alpha 1-6. Bovine liver alpha-N-acetylgalactosaminidase cleaves O-linked GalNAc. On the basis of these results, the A-chain of alpha 2 HS-glycoprotein was found to possess two biantennary N-glycans and two O-linked trisaccharides.

Blood Proteins↗

PubMed1992

The glycosaminoglycan composition of the lung with acute and chronic pathology and in senescence.

The content and distribution of GAGs in the anatomic structures of pathological (pneumoconiosis, pneumonia, pulmonary embolism) and senescent lungs have been measured. The total GAG content of the lung structures, except central bronchi is generally lower than normal in the pathological lungs. The GAG distribution in the pleura (DS predominant), central bronchi (C6S predominant), arteries, veins and 'total lung' is similar to the corresponding normal distribution. The other notable observations are: the concentration of HA in peripheral bronchi and alveoli is increased possibly in response to the high local concentration of coal dust; an age related GAG switch from DS in the arteries of the young to C6S in the arteries of the mature lung is confirmed; the arterial GAG content generally increases with age up to age 103 in the male; the arteries of a female smoker display the mature male pattern of GAG composition. The data suggest that gender, smoking and age, more than acute pathology, determine the GAG composition of the anatomic structures of the lung.

Adolescent↗

PubMed1992

Amino acid sequence of human plasma galactoglycoprotein: identity with the extracellular region of CD43 (sialophorin).

The amino acid sequence of galactoglycoprotein purified from human plasma was elucidated to 75% completeness by using chemical degradation of peptides and glycopeptides derived from digests of the protein with seven specific proteases. This sequence represents a polypeptide chain of approximately 220 amino acid residues including a high content of serine, threonine, alanine, and proline with one N-linked and multiple O-linked glycans. Comparison of peptide sequences from the native galactoglycoprotein and the deglycosylated derivative demonstrated the locations of 25 sites of O-glycosylation and three serine sites that are not glycosylated. The homogeneous N terminus was established as serine. C-terminal analysis revealed multiple C-terminal residues, suggesting that galactoglycoprotein molecules are of varying lengths. A search of a protein data base revealed that the galactoglycoprotein polypeptide is identical to the N-terminal (extracellular) polypeptide region of the blood-cell surface molecule CD43 (sialophorin, leukosialin). Further support of the relatedness of these molecules was obtained by immunoprecipitation of 125I-labeled galactoglycoprotein by monoclonal anti-CD43 antibodies. The composition and properties of the molecules together with the known structure of the gene encoding CD43 suggest that galactoprotein is derived by proteolytic cleavage from transmembrane "hexasaccharide CD43," known to be expressed on neutrophils, activated T lymphocytes, and platelets.

Amino Acid Sequence↗

PubMed1992

Primary squamous cell carcinoma of the stomach in a seventeen-year-old boy.

Primary squamous cell carcinoma (SCC) of the stomach is extremely rare and thought to arise from ectopic squamous epithelium, which in turn could either result from the squamous metaplasia of the gastric mucosa or be congenital in origin. We report herein a case of SCC of the stomach in a 17-year-old male, who died 1 year after undergoing a gastrectomy. To our knowledge, this is the youngest case of primary SCC of the stomach reported in the literature. Further speculative possibilities of the development of primary gastric SCC are discussed following the presentation of this case.

Adolescent↗

PubMed1992

[Effectiveness and tolerance of genetically engineered vaccines for hepatitis B--a comparative study].

The two hepatitis B vaccines produced by gene technology that are presently available in Germany, were compared in respect of efficacy and tolerance in 80 nurses (female and male) who were under training. Both vaccines proved to be highly effective and well tolerated. In respect of the achieved anti-HBs titer, however, the two vaccines differed significantly from each other. Using the 20 micrograms HBs antigen, the antibody titers obtained were higher by a factor of 1.8. The article gives update recommendations in respect of hepatitis B vaccination as a preventive measure in risk groups.

Adolescent↗

PubMed1992

Sodium fluoride-induced gastric mucosal lesions: comparison with sodium monofluorophosphate.

In a randomized double-blind study with two parallel groups of 10 male healthy volunteers each the response of gastric mucosa after a 7 days ingestion of sodium fluoride tablets (NaF) or sodium monofluorophosphate tablets (MFP) was compared. Gastroscopic evaluations were performed before treatment, day 1 and day 7. Simultaneously blood samples were collected for determination of laboratory data and serum fluoride values. In the MFP-group no severe gastric lesions were observed, whereas in the NaF-group in 7 of the 10 subjects significant gastric mucosal lesions including acute hemorrhages and free blood in the gastric lumen were found. The differences of the lesions scores in both groups were statistically significant (p = 0.0015). The serum fluoride content was comparable in both treatment groups. Possible adverse drug reactions were reported in 4 subjects with NaF and in 1 subject with MFP. In summary, under the experimental conditions used MFP is well tolerated by the stomach while NaF produces significant gastric mucosal lesions.

Adult↗

PubMed1991

Evidence for an involvement of NMDA and non-NMDA receptors in synaptic excitation of phrenic motoneurons in the rabbit.

The action of endogenous excitatory amino acids on phrenic motoneurons was studied in anesthetized, vagotomized, paralyzed and artificially ventilated rabbits. The NMDA receptor antagonists APV and ketamine, as well as the non-NMDA receptor antagonists GAMS and DNQX were administered by microinjection into the ventral horn of the spinal segments C3-C5. Injection of each antagonist resulted in a reversible reduction of the phrenic nerve activity. Results suggest an important function of endogenous excitatory amino acids in the excitation of phrenic motoneurons. NMDA as well as non-NMDA receptors are involved. The functional role of both receptor types in bulbospinal neurotransmission is discussed.

2-Amino-5-phosphonovalerate↗

PubMed1991

The effect of the carbohydrate moiety upon the size and conformation of human plasma galactoglycoprotein as judged by electron microscopy and circular dichroism. Structural studies of a glycoprotein after stepwise enzymic carbohydrate removal.

Galactoglycoprotein is a unique human plasma protein [76% carbohydrate (23% N-acetylneuraminic acid, 20% galactose, 3% mannose, 1% fucose and 29% N-acetylgalactosamine plus N-acetylglucosamine) and 24% polypeptide, a single polypeptide chain of about 200 amino acid residues that is high in serine and threonine content] [Schmid, Mao, Kimura, Hayashi & Binette (1980) J. Biol. Chem. 255, 3221-3226]. Highly purified exoglycosidases with well-defined specificities were used to prepare five derivatives of galactoglycoprotein in which sequential residues of N-acetylneuraminic acid, galactose, N-acetylglucosamine, a second galactose and N-acetylgalactosamine were removed with 83% of the total carbohydrate cleaved. C.d. shows that native galactoglycoprotein and all derivatives in aqueous buffer are predominantly random coil, suggesting that removal of a large number of electrostatic net charges, as well as the major portion of the carbohydrate moiety, does not alter the secondary structure of the polypeptide chain. Examination of the size and conformation of tungsten-shadowed galactoglycoprotein and asialo and agalacto derivatives by electron microscopy shows the size and conformation of all three preparations to be similar, with only minor differences in particle length and width.

Antigens, CD↗

PubMed1991

[Tumor recurrence at the neck in papillary thyroid gland cancer. A statistical analysis of the recurrence probability after radical surgery].

308 cases of papillary thyroid carcinoma (82.6% of our patients operated on between 1952 and 1987) who had undergone potentially curative surgery were analysed postoperatively. The follow-up ranges from 1 month to 29.4 years (median 4.58 years). In 32 cases (10.4%) a cervical tumour recurrence (local recurrence and/or cervical lymph nodes) was found. 8 of these are not free of tumour at the end of the follow-up, 6 had died of thyroid carcinoma (case fatality rate 18.8%, mortality rate 66.7%, in the entire material 2.9% and 29.0% respectively). The cumulative recurrence rate is 9.98% after 5 years and 16.98% after 10 years. A statistical analysis of the probability of recurrence was carried out only for patients who could be followed at least 5 years or those who died within 5 years. Age, sex, stage of tumour and histological criteria were taken into account as statistical variables. The state of cervical lymph nodes, the differentiation of the tumour and the patients' sex turned out to be determining factors for tumour recurrence after 5 years. In order to improve the recurrence rate a differentiated surgical radicality, depending on the above mentioned variables, is recommended.

Adolescent↗

PubMed1991

Fractionation of jelly substance of the sea urchin egg and biological activities to induce acrosome reaction and agglutination of spermatozoa.

Jelly coat substance surrounding the egg of the sea urchin, Hemicentrotus pulcherrimus, was fractionated by gel filtration and three fractions designated A, B, and C were obtained which mainly consisted of fucose sulfate, sialic acid, and protein, respectively. The biological activities of the fractions were examined for induction of acrosome reaction (AR) and agglutination of spermatozoa. Only fraction A, a fucose-rich glycoprotein fraction, had activities for both AR and agglutination. Fraction A was found to lose activity for AR but to retain activity for agglutination after pronase digestion. Pronase-digested fraction A was further fractionated by the same gel filtration and three fractions designated P1, P2, and P3 were obtained, which contained mainly fucose sulfate, sialic acid, and proteinous material, respectively. These fractions had no activity for AR but activity for agglutination resided in fraction P1, a fucose sulfate fraction. Furthermore, beta-elimination of the jelly substance was carried out to separate protein and fucose sulfate polysaccharide and three fractions designated E1, E2, and E3 were obtained by gel filtration, of which the fucose-rich fraction (E1) exhibited activities for both AR and agglutination, and the sialoprotein fraction (E2) retained activity only for AR. However, the activity for AR of both fractions was destroyed by pronase digestion. These results suggest that activity to induce AR resides in the protein moiety of fucose-rich glycoprotein and activity for agglutination resides in the fucose sulfate polysaccharide moiety of the same glycoprotein of the jelly substance.

Acrosome↗

PubMed1991

Endogenous activation of NMDA and non-NMDA glutamate receptors on respiratory neurones in cat medulla.

The aim of this study was to evaluate the involvement of dicarboxylic amino acid neurotransmission in the periodic discharges of respiratory neurones. Respiratory neurones of the ventral and dorsal respiratory groups in the medulla of the cat were subjected to iontophoretic applications of (1) N-methyl-D-aspartate (NMDA) and a blocker of the NMDA subtype of glutamate receptor, D-2-amino-7-phosphonoheptanoic acid (AP7) and (2) an agonist and an antagonist of the non-NMDA subtypes of receptor: quisqualate and 6,7-dinitroquinoxaline-2,3-dione (DNQX), respectively. All five main types of respiratory neurones (all-, early- and late-inspiratory, transitional "off-switch", late expiratory) were excited by NMDA and quisqualate. Both agonists increased the peak firing rate but exerted different effects on the discharge pattern of respiratory neurones, within the respiratory cycle. Quisqualate induced discharges in the "silent" period of the neurone more readily than did NMDA which, in turn had a more pronounced effect during the burst period of the neurone. The effects of quisqualate and NMDA were suppressed by prior application of their selective antagonists, AP7 and DNQX. These antagonists decreased the spontaneous neuronal discharge of all cell types, throughout the entire firing phase, by a maximum of 24-63% with AP7 and by 30-50% with DNQX. The non-selective antagonist, gamma-D-glutamyl-glycine and the selective NMDA antagonists, CPP and MK-801, were also effective. It is concluded that respiratory neurones, of all types, within the medullary respiratory network are subjected to endogenous glutamate-like excitations, which may possibly shape the respiratory train of action potentials through the sequential activation of non-NMDA and NMDA subtypes of receptor.

2-Amino-5-phosphonovalerate↗

PubMed1991

Glycine receptor-mediated fast synaptic inhibition in the brainstem respiratory system.

The involvement of glycinergic neurotransmission in the central regulation of respiration was investigated by administration of specific receptor agonists and antagonists into the 4th cerebral ventricle of the rabbit. Central respiratory activity was assessed by cycle-triggered averaging of phrenic nerve activity (PNA). Glycine reduced the peak amplitude of PNA and increased the duration of the respiratory phases. Conversely, strychnine decreased the duration of both phases, being more effective in expiration. Strychnine converted inspiratory ramp activity to a decrescendo type of pattern, with the highest discharge activity present at the onset of the inspiratory phase. Strychnine induced tonic PNA lasting throughout expiration with a decrescendo type of activity. In many cases strychnine induce apneusis with tonic PNA being at a level of about 2/3 of its maximum value during control. We conclude that glycinergic neurotransmission is important for the maintenance of the respiratory rhythm as well as the generation of normal respiratory pattern. Glycine could be involved in phasic as well as tonic inhibitory neurotransmission within the central respiratory system.

Animals↗

PubMed1991

Focal blockade of single unit synaptic transmission by iontophoresis of antagonists.

We have assessed the use of iontophoresis for investigating the pharmacology of synaptic transmission from individual presynaptic neurones in-vivo, by modifying extracellular focal synaptic potentials (FSPs) recorded by spike-triggered averaging. FSPs from two types of excitatory neurone (muscle spindle primary afferents and expiratory bulbospinal neurones) and from one inhibitory interneurone were studied in the thoracic ventral horn of anaesthetized cats. The antagonist of excitatory amino acids at non-NMDA receptors, DNQX, blocked the FSPs from the first two, as did bicuculline for the third. Thus the FSPs were generated by excitatory amino acids acting via non-NMDA receptors and GABA, respectively. The postsynaptic neurones were probably motoneurones. Merits and limitations of the method are discussed.

Animals↗

PubMed1991

A sugar-specific porin, ScrY, is involved in sucrose uptake in enteric bacteria.

During the molecular analysis of a plasmid-coded sucrose metabolic pathway of enteric bacteria, a gene, scrY, was found whose product, ScrY, had all the properties of a bacterial porin (Schmid et al., 1988). Loss of this protein (Mr 58 kDa), localized in the outer membrane, led, as shown here, to an increase in the apparent Km for sucrose transport in whole cells from 10 microM in wild-type cells to 300 microM in mutant cells. This contrasts with the Km for sucrose phosphorylation as measured in membrane vesicles from mutant and wild-type cells, which remained unchanged at about 10 microM, and reflects the activity of the sucrose-specific Enzymell of the phosphoenolpyruvate-dependent carbohydrate:phosphotransferase system (PTS) responsible for uptake through the inner membrane. Furthermore, the presence of ScrY restored growth on maltodextrins in cells devoid of LamB, thus complementing the lack of this maltoporin. The amino acid sequence deduced from the DNA sequence was determined for the plasmid-coded and the ScrY porin coded in the chromosome of Klebsiella pneumoniae. Both show high identity (86%) to each other, and to the channel domain of LamB, further corroborating the conclusion that they constitute porins.

Amino Acid Sequence↗

PubMed1991

Molecular analysis of two fructokinases involved in sucrose metabolism of enteric bacteria.

Sucrose-positive derivatives of Escherichia coli K-12, containing the plasmid pUR400, and of Klebsiella pneumoniae hydrolyse intracellular sucrose 6-phosphate by means of an invertase into D-glucose 6-phosphate and free D-fructose. The latter is phosphorylated by an ATP-dependent fructokinase (gene scrK of an scr regulon) to D-fructose 6-phosphate. The lack of ScrK does not cause any visible phenotype in wild-type strains of both organisms. Using genes and enzymes normally involved in D-arabinitol metabolism from E. coli C and K. pneumoniae, derivatives of E. coli K-12 were constructed which allowed the identification of scrK mutations on conventional indicator plates. Cloning and sequencing of scrK from sucrose plasmid pUR400 and from the chromosome of K. pneumoniae revealed an open reading frame of 924 bp in both cases--the equivalent of a peptide containing 307 amino acid residues (Mr 39 and 34 kDa, respectively, on sodium dodecyl sulphate gels). The sequences showed overall identity among each other (69% identical residues) and to a kinase from Vibrio alginolyticus (57%) also involved in sucrose metabolism, lower overall identity (39%) to a D-ribose-kinase from E. coli, and local similarity to prokaryotic, and eukaryotic phosphofructokinases at the putative ATP-binding sites.

Amino Acid Sequence↗

PubMed1991

The sugar-specific outer membrane channel ScrY contains functional characteristics of general diffusion pores and substrate-specific porins.

Escherichia coli K-12 strain PS1-28-37 carries the multicopy plasmid pPSO28-37 containing a DNA fragment coding for two of the proteins that enable bacteria to utilize sucrose as sole carbon source. One of the different gene products of the plasmid is the outer membrane protein, ScrY. This protein was isolated and purified by chromatography across a gel filtration column. Reconstitution experiments with lipid bilayer membrane demonstrated that ScrY formed ion-permeable channels with properties very similar to those of general diffusion pores of enteric bacteria. The presence of sugars in the aqueous phase led to a dose-dependent block of ion transport through the channel, like the situation found with LamB (maltoporin) of Escherichia coli and Salmonella typhimurium. The binding constants of a variety of different sugars were determined. The stability constant for malto-oligosaccharide binding increased with increasing numbers of glucose residues. Disaccharides generally had a larger binding constant than monosaccharides. The binding of different sugars to ScrY and LamB of E. coli is discussed with respect to the kinetics of sugar movement through the channel.

Bacterial Outer Membrane Proteins↗

PubMed1991

GABAA receptor mediated fast synaptic inhibition in the rabbit brain-stem respiratory system.

The involvement of GABA mediated neurotransmission in the central control of respiration was investigated by administration of the specific GABAA receptor agonist muscimol and the specific GABAA receptor antagonist biculline into the fourth cerebral ventricle of the rabbit. Cycle-triggered averaging of the phrenic nerve activity (PNA) was used to quantify drug-induced changes of the central respiratory pattern. Muscimol reduced the peak amplitude of PNA and increased the duration of the respiratory phases. High amounts of muscimol led to a long-lasting but reversible central apnea. Bicuculline very effectively blocked the effects of externally applied muscimol. Blockade of intrinsically active GABAergic neurotransmission by bicuculline resulted in a multitude of effects. Peak amplitude of PNA increased whereas the duration of both inspiration and expiration decreased. In this respect, effects of bicuculline and muscimol were complementary. Bicuculline reduced the slope of the inspiratory ramp, increased postinspiratory activity and induced an augmenting type of discharge activity in the last part of expiration resulting in a smooth transition between expiration and inspiration. In some cases the respiratory modulation was completely lost and PNA became perfectly tonic. This 'apneustic' type of respiratory pattern could be transformed into rhythmic breathing by increasing the respiratory drive. We conclude that neurotransmission via GABAA receptors is important for the maintenance of respiratory rhythm as well as the generation of normal respiratory pattern.

Animals↗

PubMed1990

Concurrent fast and slow synchronized efferent phrenic activities in time and frequency domain.

In urethane-anesthetized or decerebrated vagotomized rabbits efferent multifiber activity of the phrenic nerve was investigated for synchronized activities both in time and frequency domains. When respiratory drive was steadily increased by either an elevation of end-tidal CO2 concentration or i.v. administration of 4-aminopyridine, medium-frequency oscillations (MFO) first increased, then decreased and finally became absent. The power of high-frequency oscillations (HFO) steadily rose with increasing respiratory drive. In contrast to HFO which revealed a unimodal spectral peak of mostly small bandwidth, the MFO spectrum in most cases consisted of a broad complex. This complex in some cases was composed of two distinct peaks, i.e. MFO were heterogenous. The low- and high-frequency fractions of the MFO complex were related predominantly to the first and last third of inspiration, respectively. Examination of the on-going multifiber activity of the phrenic nerve with an expanded time scale revealed that lower frequency MFO probably result from synchronized ramp-like wave activity during early and mid-inspiration. The duration of the observed ramps well matched the corresponding MFO frequency. We suggest that these ramps might result from propagated synchronized waves of high-threshold phrenic motoneurons. During the last part of inspiration, however, MFO, like HFO, resulted from burst-like synchronized discharge of phenic motoneurons. Thus HFO are superimposed on ramp-like and burst-like activity of the MFO. It is assumed that the decline of MFO at high respiratory drive may be due to the increasing strength of HFO bursts which interrupt ramp activity in the MFO range and thus let MFO appear 'invisible' to the recording electrode. Both MFO and HFO were visually detectable in postinspiration.

4-Aminopyridine↗