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Biomedical subjects

K Schmid

Publications and source records attributed to K Schmid.

At least 127 records · Page 7Linked to original sources
PubMed1987

Three forms of BRP-2 (bone resorptive proteins) from human cancer ascites fluid and their relationship to human serum alpha-2 HS-glycoprotein.

Two new forms of BRP-2, a previously described bone resorptive protein, were purified from ascites fluids obtained from patients with hypercalcemia and metastatic bone cancer. The apparent molecular weights of BRP-2 and of these two proteins were 52,000, 48,000, and 46,000, respectively, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The three proteins have essentially the same amino acid compositions but differ with respect to their carbohydrate moieties. The amino-terminal amino acid sequences of the three glycoproteins were identical to each other as well as to human serum alpha 2HS-(human serum) glycoprotein. The relationship of the three forms of BRP-2 to alpha 2HS was also established immunochemically. The ascites proteins, as well as alpha 2HS, on a molar basis, were approximately one-tenth as potent as bovine parathyroid hormone fragment (1-34) in their abilities to stimulate calcium release from bone in vitro. This study describes for the first time a possible function for human serum alpha 2HS.

Amino Acid Sequence↗
PubMed1987

Reference master: a microcomputer-based storage and retrieval system for bibliographic references.

A complete system for housekeeping and retrieval of bibliographic references managing individual reprint collections is described. By the use of special hardware and individual data base software even large reprint collections in the range up to 65,000 papers are handled economically. A fast 8-bit microprocessor (HD 64180) in combination with a Winchester hard disk drive serves as the basis for rapid access to the desired information. An efficient string search algorithm written in assembly language guarantees a fast operation with a search speed of more than 6,000 entries/minute. The system cannot only prepare reference lists and reference files, but also incorporates an editor and maintains the control whether reprints are already on file or requested. The implementation of back-up schemes assure against data losses. Using a state of the art design single board computer and the most recent mass storage device technology, the system is as well small and cost effective, and thus suitable for personal use. In addition, some general questions and pitfalls concerning the management of scientific literature collections are touched upon.

Bibliographies as Topic↗
PubMed1987

Cholinergic effects on spike-density and burst-duration of medullary respiration-related neurones in the rabbit: an iontophoretic study.

Cholinoceptive properties of 180 medullary respiration-related neurones (RRN) were studied in urethane-anaesthetized rabbits. Acetylcholine (ACh) and agonists, as well as antagonists of muscarinic receptors and nicotinic receptors, were administered iontophoretically. Respiration-related neurons were classified with respect to the correlation of their activity with the activity of the phrenic nerve: phase-bound inspiratory (I) and expiratory (E) neurones and phase-spanning expiratory-inspiratory and inspiratory-expiratory neurones were discriminated. Acetylcholine altered the activity of 170 respiration-related neurones. In 49 cells the discharge-rate (f) alone was affected. In 44 respiration-related neurones the burst-duration (tbd) only was altered. In 77 respiration-related neurones the discharge rate and burst duration were affected simultaneously. Inhibitory actions of ACh prevailed over excitatory actions on inspiratory neurones. In expiratory neurones the discharge rate was increased or decreased in about the same number of cases. In most phase-spanning neurones the discharge rate was increased. Cholinergic inhibition of burst duration was observed in most respiration-related neurones. In all phase-types of respiration-related neurones muscarinic as well as nicotinic actions of ACh were demonstrated. In inspiratory and expiratory-inspiratory neurones muscarinic effects on the discharge rate prevailed over nicotinic effects. More nicotinic than muscarinic effects on discharge rate were observed in expiratory and inspiratory-expiratory neurones. Cholinergic effects on burst duration in about the same number of respiration-related neurones were mediated by muscarinic or by nicotinic receptors, respectively. Various types of cholinoceptors may be involved in these effects. The results suggest that cholinergic mechanisms play an important role in the control of the central regulation of respiratory movements. The functional significance of cholinergic effects on respiration-related neurones is discussed with special emphasis of effects on burst duration.

Acetylcholine↗
PubMed1987

A device for spike train sampling with built-in memory.

The described interface to a digital computer measures interspike interval durations with a resolution of 10 microseconds. A built-in first-in first-out (FIFO) memory relieves the host computer from frequent I/O intensive tasks. The internal FIFO buffer can store up to 512 data words (wordlength is 16 bit) and works on the dual-port principle. This way the acquisition of a neuronal spike train is completely independent of the computer's simultaneously ongoing data access. A simple handshake protocol between the interface and the computer prevents any overhead communication. The buffer architecture of the instrument releases the host computer from high speed I/O handling schemes like real-time, clock-controlled, polling or interrupt procedures, that would request assembly language support. The body of two software, driver routines in the BASIC and the PASCAL language is presented. A complete and detailed schematic diagram of the circuitry is included.

Computer Literacy↗
PubMed1987

A stepper motor-driven microelectrode positioner.

The mechanical elements and the electronic control system from a stepper motor-driven microelectrode positioner is described. The unit embodies a high-precision small step angle hybrid motor. The compact, rugged and totally concentric design of the mechanic, by a spindle mechanism achieves the necessary precision by translating the stepwise rotations of the motor into steps of linear movement. The system takes advantage of commercially available low friction parts such as ball bearings, ball bushings and axles with hardened surfaces. The related electronic control unit is designed around the most recent integrated circuitry which is both sophisticated and economical. Though the described system is designed to be built in an average departmental workshop it compares favorably with more expensive commercial units and in some aspects outperforms them.

Electrophysiology↗
PubMed1987

Beta-microseminoprotein (beta-MSP) is not an inhibin.

Beta-microseminoprotein (beta-MSP), a sperm-coating antigen isolated from human seminal plasma, has apparent structural identity with "beta-inhibin" isolated from the same source. Publication of the amino acid sequence of beta-MSP revealed a greater than 96% homology with "beta-inhibin," with only a proline-threonine substitution at positions 39 and 40, and the omission of a glycine at position 93. Due to the nearly identical sequences of "beta-inhibin" and beta-MSP, we examined the ability of beta-MSP and its tryptic peptides to inhibit basal follicle-stimulating hormone (FSH) secretion from rat pituitary cells in culture, the inhibin bioassay. Whole pituitaries collected from 250- to 300-g male rats were dispersed enzymatically and plated onto 24-well culture dishes for 3 days. beta-MSP and its tryptic peptides were dissolved in cell culture medium, applied to the pituitary monolayer cell cultures, and incubated for an additional 3 days. FSH levels in the medium were determined by radioimmunoassay. A partially purified preparation of inhibin and our in-house inhibin standard, both prepared from porcine follicular fluid (pFFl), were included in the same assay. Whereas the partially purified inhibin from pFFl showed a dose-dependent inhibition of FSH secretion, with a 50% inhibitory dose (ID50) of 50 ng, which paralleled that of the standard, beta-MSP and its tryptic peptides failed to depress FSH levels in the medium at any of the doses tested (10-10,000 ng/ml). We conclude that beta-MSP is not an inhibin under our assay conditions.

Animals↗
PubMed1987

Induction of microsomal enzymes in rat liver by oxcarbazepine, 10,11-dihydro-10-hydroxy-carbamazepine and carbamazepine.

1. The effects of the new anti-epileptic drug, oxcarbazepine, its major metabolite in man, 10,11-dihydro-10-hydroxy-carbamazepine, and carbamazepine, on hepatic microsomal enzyme activities have been studied in rats after repeated administration of equimolar doses. 2. All three compounds caused a qualitatively similar induction of the mono-oxygenase system, the greatest increase being observed in the activity of 4-nitroanisole O-demethylase. Oxcarbazepine is as potent as carbamazepine, while 10,11-dihydro-10-hydroxy-carbamazepine is a weak inducer. 3. The observation that oxcarbazepine is a potent inducer in rats but not in man is explained by the species differences in its metabolism.

Animals↗
PubMed1987

Metabolism of hydralazine in man. Part II: Investigation of features relevant to drug safety.

The metabolism of hydralazine (1-hydrazinophthalazine hydrochloride, Apresoline) was investigated in 17 hypertensive patients of known acetylator status who were chronically treated with oral doses of 50 mg b.i.d. or 100 mg b.i.d. hydralazine. The acetylator status was assessed either by the monoacetyldapsone/dapsone ratio or by the isoniazide plasma half-life. In each patient the tests were performed on two different days of treatment and they included the analyses of four hydralazine metabolites (NAc-HPZ, 3OH-MTP, MTP and TP), as well as apparent hydrazine in urine and also the determination of plasma concentrations of apparent hydralazine. All data of the two experiments performed within an interval of at least five days were in good agreement, thus indicating that the patients were in pharmacokinetic steady states. No correlation was detectable between any of the determined amounts of metabolites of hydralazine and the assigned acetylator status of the patients. On the other hand the rank order of the urinary yields of the two main metabolites NAc-HPZ and 3OH-MTP suggest to be a representative scale for the patients' status in respect to the biotransformation of the drug itself. The urinary yield of apparent hydrazine is dependent on the pH applied during the analyses and is not correlated with any of the other data recorded. The findings of the present study support the assumption that measuring a relevant prominent metabolite of the drug itself may lead to a more reliable assessment of the particular metabolic status of the patients than by classification through a non treatment related foreign compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1987

Ultrastructure, carbohydrate, and amino acid analysis of two preparations of the cercarial glycocalyx of Schistosoma mansoni.

This study determined the amino acid and carbohydrate composition of 2 cercarial glycocalyx preparations obtained after phenol-water extraction and subsequent gel chromatography. Labeled cercariae were subjected to 85% phenol, thereby dissociating the glycocalyx into the aqueous phase, which was dialyzed and chromatographed on Sepharose CL-2B or -4B in either 4 M guanidine hydrochloride (GuHCl) or 0.1% sodium dodecyl sulfate (SDS). The label eluted primarily in the void volume and was antigenic as tested with rabbit polyclonal antibodies by immunoblotting. Approximately 6 micrograms of protein and 28 micrograms of carbohydrate were obtained from 10(5) cercariae in the antigenic void volume fraction after SDS chromatography. Threonine, serine, and glutamic acid comprised 44% of the amino acid residues of the protein. The predominant sugar was fucose. Galactosamine, glucosamine, galactose, and mannose were also detected. After GuHCl chromatography, free amino acids, predominantly glycine and serine, comprised 17% of the total protein. The carbohydrate composition was similar to that of SDS-chromatographed extracts. Phenol-water extracts eluting in the void volume of Sepharose CL-2B were compared by negative staining and scanning electron microscopy with material obtained from medium in which cercariae shed glycocalyx during transformation to schistosomula. Both the isolated material and the transformation medium contained particles 20-50 nm in diameter, with subunits of 15-20 nm. These studies show that the cercarial glycocalyx is particulate, contains mainly carbohydrate and some protein, and is solubilized by phenol-water extraction.

Amino Acids↗
PubMed1986

Myocardial chondroitin sulfates D and E in a case of acute carbon monoxide poisoning.

The glycosaminoglycans of the myocardium of an individual who died of acute carbon monoxide poisoning were quantified by two-dimensional electrophoresis on cellulose acetate membranes. The total glycosaminoglycan content was found to be approximately twice the normal value. In contrast to the content of each glycosaminoglycan of the normal heart, the level of the chondroitin sulfates of this patient's myocardium was found to be markedly increased whereas that of hyaluronic acid was decreased and dermatan sulfate could not be detected. Further, this tissue contained significant amounts of keratan sulfate and an oversulfated dermatan sulfate, glycosaminoglycans not found in normal myocardium. Of particular interest was the presence of two unusual oversulfated chondroitin sulfates (chondroitin sulfates D and E).

Adult↗
PubMed1986

The complete amino acid sequence of the A-chain of human plasma alpha 2HS-glycoprotein.

Normal human plasma alpha 2HS-glycoprotein has earlier been shown to be comprised of two polypeptide chains. Recently, the amino acid and carbohydrate sequences of the short chain were elucidated (Gejyo, F., Chang, J.-L., Bürgi, W., Schmid, K., Offner, G. D., Troxler, R.F., van Halbeck, H., Dorland, L., Gerwig, G. J., and Vliegenthart, J.F.G. (1983) J. Biol. Chem. 258, 4966-4971). In the present study, the amino acid sequence of the long chain of this protein, designated A-chain, was determined and found to consist of 282 amino acid residues. Twenty-four amino acid doublets were found; the most abundant of these are Pro-Pro and Ala-Ala which each occur five times. Of particular interest is the presence of three Gly-X-Pro and one Gly-Pro-X sequences that are characteristic of the repeating sequences of collagens. Chou-Fasman evaluation of the secondary structure suggested that the A-chain contains 29% alpha-helix, 24% beta-pleated sheet, and 26% reverse turns and, thus, approximately 80% of the polypeptide chain may display ordered structure. Four glycosylation sites were identified. The two N-glycosidic oligosaccharides were found in the center region (residues 138 and 158), whereas the two O-glycosidic heterosaccharides, both linked to threonine (residues 238 and 252), occur within the carboxyl-terminal region. The N-glycans are linked to Asn residues in beta-turns, while the O-glycans are located in short random segments. Comparison of the sequence of the amino- and carboxyl-terminal 30 residues with protein sequences in a data bank demonstrated that the A-chain is not significantly related to any known proteins. However, the proline-rich carboxyl-terminal region of the A-chain displays some sequence similarity to collagens and the collagen-like domains of complement subcomponent C1q.

Amino Acid Sequence↗
PubMed1986

Dopaminergic control of respiration as shown by effects of 4-aminopyridine.

The dopaminergic control of respiration in conscious and urethane-anaesthetized rabbits, was studied by comparing the respiratory effects of 4-aminopyridine alone (4-AP; 1 mg/kg i.v.) and those after the administration of dopamine antagonists (domperidone and haloperidol; 1 mg/kg each). The respiratory rate in conscious rabbits was increased by 4-AP. After domperidone this increase was reduced and preceded by a transient decrease. In spontaneously breathing, anesthetized rabbits there was a transient reduction after which the respiratory rate was increased by 4-AP; tidal volume was affected in an inverse manner. After domperidone, the excitatory effect of 4-AP on respiratory rate and the inhibitory effect on tidal volume were blocked. The effects of 4-AP on respiratory rate were prevented by vagotomy. In anesthetized, vagotomized, paralyzed and artificially ventilated rabbits (VPV animals) the peak amplitude of the integrated phrenic nerve activity ("phrenic activity') was increased by 4-AP. After pretreatment with haloperidol this effect of 4-AP on phrenic activity was reduced while the respiratory rate was now increased. In VPV animals with denervated carotid bodies the excitatory effect of 4-AP on phrenic activity was strongly enhanced and respiratory rate was increased. These effects were slightly reduced but not blocked by haloperidol. It is concluded that endogenous dopamine is involved in the control of respiration through effects on peripheral mechanisms (inhibition of inspiratory activity and enhancement of respiratory rate) as well as on central mechanisms (stimulation of inspiratory activity and reduction of respiratory rate).

4-Aminopyridine↗
PubMed1986

The structure of sugar chains of Japanese quail ovomucoid. The occurrence of oligosaccharides not expected from the classical biosynthetic pathway for N-glycans; a method for the assessment of the structure of glycans present in picomolar amounts.

While the structure of the major oligosaccharide of Japanese quail ovomucoid was reported earlier (Hase, S. et al. (1982) J. Biochem. 91, 735-737), the structures of the minor oligosaccharide units were investigated for the first time in the present studies. For this purpose, the glycans of the protein were liberated from the polypeptide chain by hydrazinolysis. After N-acetylation, the reducing ends of the oligosaccharides obtained were coupled with 2-aminopyridine, and then the resulting fluorescent derivatives were purified by Bio-Gel P-2 column chromatography and reversed-phase HPLC. The chemical structures of two minor oligosaccharide units were determined with the aid of exoglycosidases, and by methylation analysis and Smith degradation. The results demonstrated that the ovomucoid contains the following two monoantennary glycans: Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc and Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc. The latter structure was not predicted by the classical metabolic pathway for the N-glycans to be formed. The structures of three additional minor heterosaccharides were deduced from their elution positions on HPLC together with the results of determination of their molecular sizes and the HPLC elution positions of their enzymatic degradation products. It is noteworthy that for the latter procedure for the estimation of the structures of oligosaccharides only minute quantities of glycans (several hundreds pmol) are required.

Amino Acids↗
PubMed1986

Purification and partial characterization of a Mr 52,000 glycoprotein from human cancer ascites fluid which stimulates bone resorption in vitro.

A glycoprotein which stimulates bone resorption in vitro has been purified at least 375-fold from human cancer ascites fluid. Purification was accomplished utilizing fractionation with ammonium sulfate, anion exchange chromatography, high-performance size exclusion chromatography, adsorptive chromatography on hydroxylapatite, and high-performance anion exchange chromatography. The homogeneous bone-resorptive protein possesses an apparent molecular weight of 52,000 as calculated from electrophoresis in sodium dodecyl sulfate:polyacrylamide gels. On polyacrylamide gels at pH 8.9 in the absence of sodium dodecyl sulfate, the bone-resorptive protein migrates with the mobility of an alpha 2-globulin. The amino acid composition of this protein is marked by the absence of methionine and by a relatively high content of nonpolar amino acids. The protein possesses a single amino- and a single carboxyl-terminal amino acid, alanine, and leucine, respectively. The carbohydrate moiety, comprising 20% of the total weight, consists of neutral hexoses, galactosamine and glucosamine, and sialic acids. With respect to its biological activity, the ascites glycoprotein is one-fourth as potent as parathyroid hormone, on a molar basis, in its ability to stimulate calcium release from bone explants in vitro. Calcium release is significantly decreased on heating at 60 degrees C but is not inhibited by indomethacin.

Adult↗
PubMed1986

[Malignant hemangioendothelioma of the thyroid gland].

Between 1969-1984 (16 years) 17 patients with "malignant haemangioendothelioma" of the thyroid were admitted to our services. This type of cancer is usually found in patients with a long history of goiter and is a very aggressive tumor. Infiltration of surrounding tissues is mostly responsible for death by asphyxia or uncontrollable bleeding. Some patients die also from metastases, which were seen frequently in the lungs. A precise preoperative diagnosis of the disease can be achieved rarely, histological classification has improved using immunohistochemical assays of Factor-VIII antigen in tumor tissue. No "prescription" for therapy can be given: results of surgery, radiotherapy and chemotherapy do not show significant differences (also in a variety of combinations). If the diagnosis is properly established, palliation will be the only therapeutic goal.

Adult↗
PubMed1986

[The percutaneous absorption of diclofenac].

The percutaneous absorption of diclofenac diethylammonium 1.16% (w/w) in a combination of emulsion cream and gel (Voltaren Emulgel) and of diclofenac sodium 1% (w/w) in a cream formulation (Voltaren cream) was investigated in guinea-pig, rabbit and man. The percutaneous absorption of diclofenac sodium in guinea-pig was 3 to 6% of the dose when the cream formulation in doses of 320, 100 or 40 mg was applied on 10 cm2 of occluded skin and left in place for 6 h. The transdermal delivery of 14C-labelled diclofenac yielded plateau plasma concentrations of radiotracer from 1.5 h after application until removal of the residual cream. Subsequently the steady state drug depots in the skin and muscle tissue were depleted promptly. During daily administration the steady state levels in the muscle tissue in proximity to the application site were about 3 times higher than in distant muscle tissue. By topical application on knee joints of rabbits diclofenac penetrated into the patellar ligament, the adipose corpus and the synovial fluid. In man the percutaneous absorption was 6% of the dose when the Emulgel formulation was spread by 5 mg/cm2 and left for 12 h on non-occluded skin. The pattern of metabolites of diclofenac in human urine was the same after topical and oral administration. In man, upon daily topical administration of 3 times 2.5 g cream formulation (10 mg/cm2) the diclofenac steady state plasma levels were 20 to 40 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗