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Biomedical subjects

J Schmid

Publications and source records attributed to J Schmid.

At least 91 records · Page 5Linked to original sources

Evidence for nosocomial transmission of Candida albicans obtained by Ca3 fingerprinting.

The moderately repetitive sequence Ca3 was used to fingerprint Candida albicans isolates from 32 patients hospitalized for more than 3 days, 17 recent admissions or outpatients, and 8 recently readmitted patients and 10 commensal isolates from the community in Wellington, New Zealand, plus isolates from 21 hospitalized patients, 26 outpatients or recent admissions, 4 recently readmitted patients, and 10 healthy individuals in the community in Auckland, New Zealand. In Wellington, isolates from patients hospitalized in Wellington Hospital for more than 3 days were genetically significantly less diverse than were isolates from outpatients or recent admissions or isolates from healthy individuals in the community. In addition, two clusters of genetically similar strains were isolated from hospitalized patients significantly more often than from other individuals. These observations provide evidence (albeit indirectly) for nosocomial transmission of hospital-specific C. albicans strains. In contrast, no indication of hospital-specific transmission of C. albicans was found in Auckland Hospital. Since these results were obtained under conditions in which no candidiasis outbreak occurred in either hospital, they also suggest that Ca3 fingerprinting may be a useful tool in preventive nosocomial infection control programs, allowing assessment of the extent of C. albicans transmission occurring in a hospital.

Adolescent↗

Meloxicam: metabolic profile and biotransformation products in the rat.

1. The metabolic fate of 14C-labelled meloxicam was investigated in the urine and bile of rat following oral and intraduodenal administration. Structural elucidation of metabolites was performed by nuclear magnetic resonance, mass spectrometry (electron impact and fast atom bombardment). 2. A mean total of 76.3% 14C-radioactivity was recovered in urine over 96 h, with the remainder in the faeces. The metabolic pattern in the excreta was independent of dose (1 versus 10 mg/kg) and collection period (0-8 versus 24-48 h). In bile one of the main metabolites was absent. 3. Meloxicam underwent extensive metabolism with only small amounts of unchanged drug recovered in the urine (< 0.5%) or bile (4.5%). Principal routes of biotransformation were: oxidation of the 5-methyl group of the N-heteroaryl-carbamoyl side chain to yield the 5'-hydroxymethyl derivative (33% of metabolites in urine, 22% in bile) and the 5'-carboxy derivative (16% in urine, 49% in bile). Oxidative cleavage of the benzothiazine-ring yielded an oxamic acid metabolite in urine (23.5%), which was not present in bile. 4. The introduction of a methyl-group into the N-heteroaryl-carbamoyl side chain increased lipophilicity and facilitated metabolic excretion compared with structurally related compounds.

Animals↗

Metabolism of pimobendan in long-term human hepatocyte culture: in vivo-in vitro comparison.

The aim of this study was to investigate further the potential of a new hepatocyte culture based on the hypothesis that liver cells in an appropriate in vitro environment (immobilizing gel technique) maintain high metabolic activity comparable with that in vivo. Pimobendan (UD-CG 115), a pyridazinone derivative, is a cardiotonic vasodilator that increases myocardial contractility through calcium sensitization and relaxation of vascular smooth muscle, probably due to phosphodiesterase inhibition. In man, pimobendan is O-demethylated to UD-CG 212. This latter is metabolized to O- and N-glucuronides. Pimobendan itself is also glucuronidated to a N-glucuronide. Human hepatocytes immobilized in collagen gel were incubated with pimobendan to investigate their metabolic activity in the long-term and to compare the results to the data from clinical trials. 14C-labelled pimobendan was incubated at two concentrations (10 and 100 microM) at day 3, 11 and 22 of culture, and samples were analysed after 4, 24 and 48-h incubation. Metabolic patterns were evaluated by hplc with radioactivity-, diode array-, and mass spectral-detection. In vitro, pimobendan was O-demethylated and subsequently O-glucuronidated. The rate of metabolism of pimobendan could be maintained in this culture system for > 3 weeks. However, the relative amount of a putative N-glucuronide under in vitro conditions was lower than in vivo.

Biotransformation↗

Telemicroscopy stations for telepathology based on broadband and ISDN connections.

Telemicroscopy equipment is a key tool to perform Telepathology successfully. It allows the local separation of the microscope with the tissue samples from the investigating pathologist. The Telemicroscopy stations presented provide the user with a full access to the functions such as scanning stage, focus, illumination and magnification selection of a remote microscope. One system applies as communication link a broadband video conference net of the German Telekom with full realtime capabilities and color TV-image quality. As this network provides adequate interfaces for video and computer net signals, it is well suited to establish within a short time interval a very comfortable Telemicroscopy connection without the development of additional equipment. As the broadband network is expensive the application is economically restricted to special applications. The other system relies on the narrow band connections of the ISDN telephone network. This design is inexpensive with respect to data transmission and is available nearly worldwide everywhere. But on the other hand this strategy is limited concerning realtime capabilities. To reduce these limitations to an acceptable level intelligent coding and operation concepts of the stations have to be developed.

Computer Communication Networks↗

Pharmacokinetics and metabolic pattern after intravenous infusion and oral administration to healthy subjects.

Meloxicam [4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H- 1,2-benzothiazine-3-carboxamide-1,1-dioxide] is a new nonsteroidal antiinflammatory drug belonging to the enolic acid group. In a crossover study, 30 mg 14C-labeled meloxicam was administered to four male healthy volunteers as a short-term infusion and as an oral solution. The objectives of the study were to determine the mode of elimination, the excretion balance, the in vivo binding characteristics to serum proteins, and to investigate the metabolic pattern in plasma, urine, and feces. A comparison of plasma concentration measurements of unchanged drug by a specific HPLC assay and total radioactivity by liquid scintillation counting revealed a very close conformity. Over 90% of the plasma radioactivity was represented by unchanged drug. Its terminal and dominant half-life of elimination from plasma, as determined from plasma and urinary data in this study, ranged from 12 to 17 hr in the volunteers. The serum protein binding of the radioactivity from in vivo samples was very high (99.1-99.7%). The excretion balance was complete after 6 days. Average urinary excretion of 14C-radioactivity accounted for 43% of the dose, with the remainder appearing with the feces. Meloxicam was extensively metabolized, with only traces of the drug appearing unchanged in urine and feces. The main metabolites were formed by hydroxylation and further oxidation of the methyl group of the thiazolyl moiety. In addition, two further metabolites were found, particularly in urine. Altogether, > 95% of the dose excreted could be accounted for by the metabolites identified or the parent compound itself.

Administration, Oral↗

Structural and catalytic properties of the four phenylalanine ammonia-lyase isoenzymes from parsley (Petroselinum crispum Nym.).

Near-full-length cDNAs for the four phenylalanine ammonia-lyase (PAL) isoenzymes in parsley (Petroselium crispum Nym.) were cloned and the complete amino acid sequences deduced. Fusion proteins with glutathione S-transferase were expressed in Escherichia coli, purified and cleaved. All of the resulting phenylalanine ammonia-lyase proteins, as well as the fusion proteins, were catalytically active. The turnover number of one selected isoenzyme, PAL-1, was estimated to be around 22 s-1 for each active site. In contrast to a certain degree of differential expression in various parts of parsley plants, the four phenylalanine ammonia-lyase isoenzymes exhibited very similar apparent Km values for L-phenylalanine (15-24.5 microM) as well as identical temperature (58 degrees C) and pH (8.5) optima. All of them were competitively inhibited by (E)-cinnamate with similar efficiency (Ki values: 9.1-21.5 microM), lacked cooperative behaviour, and accepted L-tyrosine as a substrate with low affinity (Km values: 2.6-7.8 mM). These results suggest that the occurrence of multiple gene copies has a function other than encoding isoenzymes with different enzyme kinetic properties.

Amino Acid Sequence↗

Assay of zatebradine in plasma by fully automated sample clean-up, capillary gas chromatography and ammonia chemical ionisation mass spectrometry.

A method has been developed for the measurement of zatebradine (UL-FS 49), a heart-rate lowering drug, suitable for the treatment of stable angina pectoris. The method comprises a fully automated liquid-solid extraction using a Zymark Benchmate, a capillary gas chromatography and ammonia chemical ionisation (CI) mass spectrometry using hexadeuterated zatebradine for the internal standard. The assay has a mean between-batch imprecision of 4.9% and a mean inaccuracy of 1.5%. The calibration curve covers the range of 1-30 ng/ml. About 60 samples can be handled per day. The assay has been successfully applied to human pharmacokinetic studies.

Ammonia↗

Abundance of transcripts specific for genes encoding enzymes of the prechorismate pathway in different organs of tomato (Lycopersicon esculentum L.) plants.

The abundance of transcripts specific for several tomato (Lycopersicon esculentum L.) genes encoding enzymes of the prechorismate pathway was analyzed in different organs of mature plants utilizing a dot-blot assay which was developed for this purpose. The transcript levels were determined for two 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (EC 4.1.2.15), one shikimate kinase (EC 2.7.1.71), one 5-enolpyruvylshikimate 3-phosphate synthase (EC 2.5.1.19), and two chorismate synthase (EC 4.6.1.4) genes in leaves, cotyledons, stems, roots, and flowers. These organ-specific expression patterns were compared with that of the phenylalanine ammonia-lyase (EC 4.3.1.5) gene family of tomato.

Base Sequence↗

Membrane permeability is unnecessary for guided generation of new bone. An experimental study in the rabbit.

The aim of this investigation was to test the hypothesis that membrane permeability is necessary in bone formation using the principle of guided tissue regeneration. On the forehead of 8 rabbits, titanium test cylinders were anchored in the calvaria. These cylinders were either covered by an expanded polytetrafluoroethylene (ePTFE) membrane generating a chamber for bone formation or they were sealed off by cast titanium. The implanted cylinders were covered by resuturing the periosteum and the cutaneous flap. After 8 months of healing, new bone had formed in all cylinders in all animals irrespective of whether the chamber for bone formation was sealed off by cast titanium or the ePTFE membrane. Based on these results, we conclude that permeability of the membrane is not necessary in the guided generation of new bone.

Animals↗

[The introduction of paddocks in circus elephant husbandry].

The guidelines for the keeping, the education and the using of animals in circuses and similar institutions, which are made in connection with the law for prevention of cruelty to animals, claim to keep elephants daily one hour unshackled in the group in a paddock. This paper deals with the effect of the paddock to the social, the play, and the comfort behaviour, and the stereotyped movements of circus elephants. Basically for the behaviour of kept elephants are results of observations in nature. A pilot study with 29 elephants in four circuses showed that the paddock enabled the elephants to carry out social and comfort behaviour more frequently than in the shackled keeping. The stereotyped movements were nearly absent by keeping the elephants in the paddock. If they keep shackled, this behaviour anomaly will take up much time.

Animal Welfare↗

Cloning and expression in yeast of a higher plant chorismate mutase. Molecular cloning, sequencing of the cDNA and characterization of the Arabidopsis thaliana enzyme expressed in yeast.

Chorismate mutase (EC 5.4.99.5) catalyzes the first step in the branch of the shikimate pathway which leads to the aromatic amino acids, phenylalanine and tyrosine. We have isolated a cDNA for this enzyme from the higher plant, Arabidopsis thaliana, by complementing a yeast strain (aro7) with a cDNA library from A. thaliana. This is the first chorismate mutase cDNA isolated from a plant. It encodes a protein of 334 amino acids. The identity of the deduced amino acid sequence is 41% to the chorismate mutase sequence from Saccharomyces cerevisiae. The N-terminal portion of the deduced amino acid sequence has no homology to the S. cerevisiae sequence but resembles known plastid-specific transit peptides. The A. thaliana chorismate mutase expressed in yeast revealed allosteric control by the three aromatic amino acids, as previously described for plastidic chorismate mutase isozymes.

Amino Acid Sequence↗

Differential expression of tomato (Lycopersicon esculentum L.) genes encoding shikimate pathway isoenzymes. I. 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase.

Tomato (Lycopersicon esculentum L. cv. UC82b) was found to contain two distinct 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase genes that are differentially expressed. The corresponding cDNAs were isolated and characterized. Both genes code for putative plastidic DAHP synthase isoforms. The deduced amino acid sequences are 79% identical. A comparison of the known Solanaceae DAHP synthases indicates two distinct conserved isoforms. The steady-state levels of transcripts of the two tomato genes differ in all organs analysed.

3-Deoxy-7-Phosphoheptulonate Synthase↗

Differential expression of tomato (Lycopersicon esculentum L.) genes encoding shikimate pathway isoenzymes. II. Chorismate synthase.

In tomato (Lycopersicon esculentum L. cv. UC82b) two distinct genes (designated LeCS1 and LeCS2) code for chorismate synthase. The corresponding cDNAs have been isolated and characterized. The deduced amino acid sequences are 88% identical. Both genes encode chorismate synthases with putative plastid-specific N-terminal transit peptides. The two genes are predominantly expressed in flowers and roots and, to a lesser extent, in stems, leaves, and cotyledons, but the steady-state levels of LeCS1-specific transcripts are consistently higher than those of the LeCS2-specific transcripts.

Amino Acid Sequence↗

Monoclonal antibody uptake in B-cell lymphomas: experimental studies in nude mouse xenografts.

Accumulation of radiolabelled monoclonal antibodies (mAb) in human B-lymphoma xenografts was found to result in two distinct patterns. The basic elements leading to these patterns were elucidated by autoradiographic and immunohistological analysis applied to the nude mouse xenografts BJAB and OCI.LY1. With BJAB, accumulation occurred exclusively in peripheral cell layers of the lymphoma nodule, while central areas were not accessible irrespective of mAb dose. This feature was the consequence of an inefficient transport across intratumoral vessels together with peripheral mAb supply through a subcapsular pseudosinus. With OCI.LY1, intratumoral vessels showed generalized leakiness. Furthermore, interstitial transport was operative to a fair extent, such that in early images multiple sites of mAb extravasation were obvious, which coalesced during the course of prolonged uptake. The pattern of peripheral mAb uptake resulted in a low overall tumour uptake, while multifocal uptake yielded substantial accumulation values.

Animals↗

Genetic similarity of Candida albicans strains from vaginitis patients and their partners.

The moderately repetitive sequence Ca3 was used to fingerprint strains of Candida albicans isolated from vulvovaginal infections of 10 women and strains isolated from their male partners. The Dendron software package was then used to compare the DNA fingerprints of these strains with those of vaginal commensals from women from the same geographical locale, vaginal commensals from women from a different geographical locale, and commensals from male partners of asymptomatic women from the same geographical locale. The results demonstrate that, in the majority of cases (8 of 10), strains from symptomatic patients and their partners are either identical or more similar to each other than to other strains, infecting strains do not represent a group genetically distinguishable from vaginal commensal isolates from women from the same geographical locale, and both infecting strains and commensals from individuals in the test locale can be distinguished from commensals obtained in another geographical locale. The results also suggest that women with vaginal infections are responsible for strain replacement in their male partners.

Adult↗