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Biomedical subjects

K Schmid

Publications and source records attributed to K Schmid.

At least 73 records · Page 4Linked to original sources

[The importance of formic acid excretion in the urine for environmental and occupational medicine questions].

The suitability of the formic acid excretion in the urine as a parameter for the biological monitoring of inhalational exposure to formaldehyde is discussed controversially. We investigated persons not occupationally exposed to formaldehyde (n = 70) to determine possible influencing factors on the physiological excretion of formic acid. Following this we carried out a study on medical students (n = 30), who during an anatomical dissection course were exposed to a short but intensive inhalational exposure to formaldehyde, as well as investigations on employees of a pathological-anatomical laboratory (n = 8) in order to observe the course of the formic acid excretion in the urine during a working week with a continuous exposure to formaldehyde below or within the range of the MAK value (0.5 ppm). It was seen that the formic acid excretion in the urine with non-exposed persons is subject to considerable inter and intraindividual fluctuations (at a maximum by a factor of 30). In addition to differences in the endogenous formation of formates an important influencing factor is probably the uptake of food containing formic acid or its precursors. A value of 23 mg formic acid/g creatinine is given as the upper norm level (95th percentile) of adults. In the groups who were exposed to formaldehyde, in some cases considerably above the MAK value, we were able to detect no significant increase in the formic acid concentration in the urine. After a short but intensive exposure to formaldehyde (0.32-3.48 ppm) the formic acid concentration in the urine did not change significantly with an average formic acid concentration in the urine before exposure of 6.5 mg/g creatinine (central 50% range: 3.5-14.2 mg/g creat.) and after exposure of 6.0 mg/g creatinine (central 50% range: 4.4-10.9 mg/g creat.). There was no significant relationship between the individual change in the formic acid concentration in the urine (in mg/g creatinine) and the inhalational exposure to formaldehyde determined through personal air sampling (r = 0.079). In the course of a working week with a continuous exposure to formaldehyde (0.03-0.83 ppm) there was after relating the values to creatinine a continuous increase in the median to 22.3 mg/g creat. with a starting value of 8.7 mg/g creat. The change proved, however, for the number of cases investigated not to be significant. In particular there was no linear correlation detectable between the individual changes in the formic acid excretion in the urine and the formaldehyde concentrations in the breathing zone determined by personal air sampling.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗

Beta-endorphin and adrenocorticotropic hormone production during marathon and incremental exercise.

To evaluate the increases in concentration of beta-endorphin and adrenocorticotropic hormone (ACTH) 16 healthy athletes, well-trained for endurance exercise, volunteered for an exhausting incremental graded treadmill exercise and a marathon run. Maximum oxygen uptake was determined during the treadmill exercise. Venous blood samples were drawn before and after exercise, and at 30, 60 and 120 min during the recovery phase. For the marathon race venous blood was collected before, after 1 and 2 h of running and at the end, as well as at 0.5, 1, 2 and 24 h during the recovery phase. Lactate concentration, heart rate and perceived exertion were also determined at all points of blood collection. Both types of exercise led to significant increases in concentration of beta-endorphin and ACTH of similar magnitude, with beta-endorphin tending to be higher after the marathon run. The decrease of both was slower during the recovery from the marathon than after the incremental test. Concentrations of both hormones increased exponentially during the marathon run. Positive correlations between beta-endorphin and ACTH concentrations were determined at the end of both runs. It was found that incremental exhausting and prolonged exhausting endurance exercise such as marathon running induced an increase of similar magnitude in both beta-endorphin and ACTH concentration.

Adrenocorticotropic Hormone↗

Contralateral projections of thoracic respiratory interneurones in the cat.

1. Retrograde neuronal transport following small iontophoretic injections of horseradish peroxidase was used to investigate the location of neurones projecting to the thoracic ventral horn of the cat. 2. A concentration of labelled neurones was seen in the contralateral medial ventral horn at the immediately opposite rostrocaudal position. 3. The participation of respiratory interneurones in the projection was investigated by means of spike-triggered averaging, as follows. 4. Spike trains of single interneurones whose firing patterns were related to the central respiratory cycle were recorded extracellularly in the thoracic ventral horn of anaesthetized, paralysed cats. Firing patterns were defined by the construction of cycle-triggered histograms. 5. Spike-triggered averaging of the signal from an extracellular tungsten microelectrode in the opposite ventral horn was performed to test for the presence of axonal, terminal or focal synaptic potentials. 6. At least one of these types of potential was found for 34/55 units. Terminal potentials were found for thirty-one units, accompanied by focal synaptic potentials for twenty-seven units. Potentials were found for units with all types of firing patterns. Units whose activity elicited these potentials were generally located in the medial half of the ventral horn. 7. We conclude that at least 60% of the respiratory interneurones project to the immediately opposite ventral horn.

Action Potentials↗

Functional identities of thoracic respiratory interneurones in the cat.

1. Spike-triggered averaging was used to reveal focal synaptic potentials (FSPs) in the thoracic ventral horn resulting from impulses in individual respiratory interneurones situated in the contralateral ventral horn of the same segment (T6 or T7) in anaesthetized paralysed cats. 2. FSPs were of two types, negative-going or positive-going, and were of the same sign at each of several sites for each unit. These two types were interpreted as indicating excitatory or inhibitory actions respectively. 3. The positive-going FSPs were almost all the result of activity in the most strongly modulated, phasic respiratory interneurones, whereas most of the negative-going ones were derived from neurones with a continuous tonic component in their firing patterns. 4. Positive-going FSPs (particularly those from inspiratory neurones) were generally found at more ventral sites in the ventral horn than negative-going ones. 5. It is suggested that an important role for the phasically active interneurones is to provide phasic inhibition, which is combined with largely tonic excitation to produce strong respiratory modulation in the activity of other neurones in the thoracic spinal cord, particularly in motoneurones. However, some groups of respiratory interneurones, such as a group of tonic inspiratory ones which are located more dorsally than the phasic inspiratory ones, may not receive such phasic inhibition.

Action Potentials↗

Alpha 1-acid glycoprotein and peripheral nerve injury, studied with a wound chamber.

BACKGROUND: The aim of the present study is to demonstrate the distribution and quantitative changes of alpha 1-acid glycoprotein (AGP) in rat sciatic nerve subsequent to mechanical injury. AGP is a serum protein, whose level rises after injury; hence the term "acute phase reactant." AGP is synthesized mainly by hepatocytes and the production is stimulated by cytokines released by inflammatory cells. The biologic role of AGP is not known except that it has in vitro nerve growth promoting property. EXPERIMENTAL DESIGN: Impermeable silicone tubes, 10 mm long and 1.4 mm in internal diameter, were sutured to the ends of transected rat sciatic nerve. On the 1st to 21st postoperative days, the wound fluid in the tube and the rat sera were collected for protein analysis and quantitative determination of AGP. The sciatic nerves were removed and immunostained with a monoclonal antibody against rat AGP. RESULTS: The protein content in the wound fluid was 1/5 that of the serum, the proteins of the wound fluid and the serum had similar electrophoretic patterns on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. There was a parallel rise of AGP levels in serum and in wound fluid beginning 1 day after the operation reaching the highest level on the 5th day. Immunohistochemical study showed deposits of extravasated AGP in fibrin cable connecting the ends of the transected nerve, in endoneurium, perineurium, perivascular mononuclear, and mesenchymal cells of epineurium at the wound and diffusely in the entire distal nerve segment. CONCLUSIONS: Increased vascular permeability with exudation of leukocytes and plasma proteins are basic pathophysiologic reactions to injury. The wound chamber method employed in the present study may provide a useful model for investigations dealing with the roles of circulating plasma proteins and other molecules as well as local cellular products involved in wound healing and nerve regeneration.

Acute-Phase Proteins↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

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↗