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Biomedical subjects

J Schmid

Publications and source records attributed to J Schmid.

At least 19 recordsLinked to original sources

Volatile organic compounds in the exhaled breath of young patients with cystic fibrosis.

Inflammatory mediators in the exhaled breath are receiving growing medical interest as noninvasive disease markers. Volatile organic compounds have been investigated in this context, but clinical information and methodological standards are limited. The levels of ethane, propane, n-pentane, methanol, ethanol, 2-propanol, acetone, isoprene, benzene, toluene, dimethyl sulphide (DMS) and limonene were measured in repeated breath samples from 20 cystic fibrosis patients and 20 healthy controls (aged 8-29 yrs). Three end-exhaled and one ambient air sample were collected per person and analysed on a customised gas chromatography system. Intra-subject coefficients of variation ranged between 9 and 34%, and hydrocarbon breath levels were influenced by their inspired concentrations. The alveolar gradient for pentane was higher in cystic fibrosis patients than in healthy controls (0.36 versus 0.21 ppb) and inversely proportional to forced expiratory volume in one second; highest values were observed in patients with pulmonary exacerbations (0.73 versus 0.24 ppb). Cystic fibrosis patients also exhibited a lower output of DMS (3.9 versus 7.6 ppb). Group differences were not significant for ethane and the remaining substances. It was concluded that chemical breath analysis for volatile organic compounds is feasible and may hold potential for the noninvasive diagnosis and follow-up of inflammatory processes in cystic fibrosis lung disease.

2-Propanol↗

Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.

A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing propargylic ether P1' groups, was explored. In particular, compound 5h has excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-alpha production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA.

ADAM Proteins↗

Selecting representative model micro-organisms.

BACKGROUND: Micro-biological research relies on the use of model organisms that act as representatives of their species or subspecies, these are frequently well-characterized laboratory strains. However, it has often become apparent that the model strain initially chosen does not represent important features of the species. For micro-organisms, the diversity of their genomes is such that even the best possible choice of initial strain for sequencing may not assure that the genome obtained adequately represents the species. To acquire information about a species' genome as efficiently as possible, we require a method to choose strains for analysis on the basis of how well they represent the species. RESULTS: We develop the Best Total Coverage (BTC) method for selecting one or more representative model organisms from a group of interest, given that rough genetic distances between the members of the group are known. Software implementing a "greedy" version of the method can be used with large data sets, its effectiveness is tested using both constructed and biological data sets. CONCLUSION: In both the simulated and biological examples the greedy-BTC method outperformed random selection of model organisms, and for two biological examples it outperformed selection of model strains based on phylogenetic structure. Although the method was designed with microbial species in mind, and is tested here on three microbial data sets, it will also be applicable to other types of organism.

Bacteria↗

Feline uropathogenic Escherichia coli from Great Britain and New Zealand have dissimilar virulence factor genotypes.

We investigated the prevalence of 30 known virulence factor genes (VFGs) in uropathogenic E. coli (UPEC) from two geographically distinct feline populations, using a PCR-based approach. E. coli isolates were also subjected to macrorestriction analysis to assess their phylogenetic relationships. VFG profiles differed considerably according to the geographic origin of the isolates, enabling discriminant analysis to correctly predict population membership for 15/15 NZ isolates and 18/22 UK isolates. The prevalence of gene markers for P-fimbriae (PapA, PapC, PapEF, and PapG III), colicin V (CvaC), increased serum survival factor (Iss), complement resistance factor (TraT), pathogenicity-associated island (MalX), iron-regulated siderophore receptor (IreA) and haemolysin (HlyD) differed significantly between UK and NZ isolates. Significant phylogenetic differences between the two populations were also identified, but VFG profiles could not be predicted on the basis of phylogenetic relationships. Consequently, a geographically uneven distribution of certain virulence genes, independent of phylogeny, is the likely cause of VFG differences between populations. We cannot rule out that subtle differences in patient disease status may have contributed to the dissimilarity of VFG profiles.

Animals↗

Axial skeletal and Hox expression domain alterations induced by retinoic acid, valproic acid, and bromoxynil during murine development.

Retinoic acid (RA) alters the developmental fate of the axial skeletal anlagen. "Anteriorizations" or "posteriorizations," the assumption of characteristics of embryonic areas normally anterior or posterior to the affected tissues, are correlated with altered embryonal expression domains of Hox genes after in utero RA treatment. These "homeotic" changes have been hypothesized to result from alterations of a "Hox cod" which imparts positional identity in the axial skeleton. To investigate whether such developmental alterations were specific to RA, or were a more general response to xenobiotic exposure, CD-1 pregnant mice were exposed to RA, valproic acid (VA), or bromoxynil (Br) during organogenesis. Additionally, the expression domains of two Hox genes, Hoxa7 and Hoxa10, were examined in gestation day (GD) 12.5 embryos obtained from control, RA, VA, or Br, treated gravid dams exposed on GD 6, 7, or 8. The anterior expression boundary of Hoxa7 is at the level of the C7/T1 vertebrae and that of Hoxa10 is at L6/S1. Compound-induced changes in the incidence of skeletal variants were observed. These included supernumerary cervical ribs (CSNR) lateral to C7, 8 vertebrosternal ribs, supernumerary lumbar ribs (LSNR) lateral to L1, extra presacral vertebrae, and the induction of vertebral and/or rib malformations. RA and VA administration on GD 6 caused posteriorization in the cervico-thoracic region (CSNR) while GD 8 exposure to any of the three compounds resulted in anteriorizations in the thoraco-lumbar area (LSNR and an increase in the number of presacral vertebrae). These effects occurred across regions of the axial skeleton. Analysis of gene expression demonstrated changes in the anterior boundaries of Hoxa7 expression domains in embryos treated on GD 6 and 8 with RA. VA and Br did not induce any statistically significant alterations in Hoxa7 and none of the compounds caused alterations in Hoxa10 expression domains. The studies indicate that RA GD 6 treatment-induced Hoxa7 shifts were rostral (posteriorization) while the RA-induced GD 8 anterior expression boundary shift was caudal (anteriorization), correlating with the axial skeletal changes noted. These data suggest that xenobiotic compounds such as VA and Br may induce similar axial skeletal changes by affecting different components of the developmental processes involved in the patterning of the axial skeleton.

Abnormalities, Drug-Induced↗

The impact of the weight status on subjective symptomatology of the Polycystic Ovary Syndrome: a cross-cultural comparison between Brazilian and Austrian women.

Group differences in symptomatology and symptom perception of young women ageing between 18 and 32 years suffering from polycystic ovarian syndrome (PCOS) were tested according to cultural background and weight status. In detail 31 Austrian women, living in Carinthia, Austria, and 102 Brazilian women, living in São Paulo, Brazil, were enrolled in the present study. All participants suffered from diagnosed PCOS. The prevalence of hirsutism, infertility, menstrual disturbances and overweight/obesity and their individual impact on health related quality of life were analysed. Furthermore the impact of weight status (BMI) on symptom perception was tested. It turned out, that the Brazilian sample exhibited higher prevalence of PCOS symptoms and these symptoms had a more negative impact on quality of life. The only exception was body weight. Although significantly leaner, the Austrian women showed a higher Cronin score of body weight than their Brazilian counterparts. The results of the present study may indicate that in western industrialized societies the fear of overweight is much more prevalent than in a developing country such as Brazil and thus it has more influence on the quality of life than all the other symptoms.

Adolescent↗

A DNA polymorphism specific to Candida albicans strains exceptionally successful as human pathogens.

A large proportion of infection-causing isolates of the yeast Candida albicans belong to a general-purpose genotype, identifiable by fingerprinting with the moderately repetitive sequence Ca3. The high prevalence of this group -- up to 70% in some patient categories -- suggests that its members possess genetic determinants, which enhance their success as pathogens compared to other strains. To find such determinants we are comparing the genomes of representatives of the general-purpose genotype cluster with the genomes of other strains. In this paper we describe the identification of a 985 bp HpaII fragment (MU13-4) specific to general-purpose genotype strains. The fragment was present in 90% of these strains, but only in 10% of other strains. The fragment did not hybridize with probe Ca3, used to define the general-purpose cluster. It contains elevated levels of repetitive DNA. Sequences homologous to MU13-4 are dispersed throughout the chromosomes of general-purpose strains but are rarer or absent in other strains, as judged by Southern hybridization. Using the Stanford C. albicans genome database, we have placed the MU13-4 fragment next to a CARE-1 element. We also found 79 significant homologies between parts of MU13-4 and 19 other contigs. Attempts to amplify the region surrounding the polymorphic fragment in non-general-purpose genotype strains suggest, as do the hybridization data, that the polymorphism is created by a deletion in non-cluster strains. These results show that it is possible to identify polymorphisms specific to general-purpose genotype strains. Primers against the fragment will allow PCR-based discrimination between general-purpose genotype strains and other strains, facilitating investigations aimed at determining morbidity and mortality caused by general-purpose genotype strains compared to other strains.

Base Sequence↗

Human visual function in the North Carolina clinical study on possible estuary-associated syndrome.

The U.S. Environmental Protection Agency assisted the North Carolina Department of Health and Human Services in conducting a study to investigate the potential for an association between fish kills in the North Carolina estuary system and the risk for persistent health effects. Impetus for the study was recent evidence suggesting that estuarine dinoflagellates, including members of the toxic Pfiesteria complex (TPC), P. piscicida and P. schumwayae, may release a toxin(s) that kills fish and adversely affects human health. This report describes one component of the study in which visual system function was assessed. Participants working primarily in estuaries inhabited by TPC or in off-shore waters thought not to contain TPC were studied. The potentially exposed estuary (n = 22) and unexposed offshore (n = 20) workers were matched for age, gender, and education. Visual acuity did not differ significantly between the cohorts, but visual contrast sensitivity (VCS), an indicator of visual pattern-detection ability for stimuli of various sizes, was significantly reduced by about 30% in the estuary relative to the offshore cohort. A further analysis that excluded participants having a history possibly predictive of neuropsychological impairment showed a similar VCS reduction. Additional analyses indicated that differences between the cohorts in age, education, smoking, alcohol consumption, and total time spent on any water did not account for the difference in VCS. Exploratory analyses suggested a possible association between the magnitude of VCS reduction and hours spent in contact with a fish kill. The profile of VCS deficit across stimulus sizes resembled that seen in organic solvent-exposed workers, but an assessment of occupational solvent, and other neurotoxicant, exposures did not indicate differences between the cohorts. These results suggest that factor(s) associated with the North Carolina estuaries, including the possibility of exposure to TPC toxin(s), may impair visual system function.

Analysis of Variance↗

Selective spinal anesthesia for outpatient laparoscopy. III: sufentanil vs lidocaine-sufentanil.

PURPOSE: The efficacy of low dose intrathecal lidocaine-sufentanil was compared with intrathecal sufentanil for short duration outpatient gynecological laparoscopy. METHODS: Thirteen ASA I and II patients undergoing gynecological laparoscopy were studied in a randomized double-blind trial. Patients received either intrathecal 10 mg lidocaine plus 10 microg sufentanil (Group LS) or intrathecal 20 microg sufentanil (Group S), each diluted to 3 mL with sterile water through a 27g Whitacre needle in the sitting position. Sensory and motor recovery were assessed with pinprick and a modified Bromage scale. RESULTS: One of seven Group LS patients and two of five Group S patients required conversion to general anesthesia for failed skin test with forceps. Two of the remaining three Group S patients felt sharpness with skin incision. The study was terminated early because of inadequate anesthesia in Group S. The small sample size (n = 9) made statistical analysis uninformative. CONCLUSION: Intrathecal 20 microg sufentanil is unsuitable as a sole agent for gynecological laparoscopy.

Adult↗

Temporal and local appearance of alkaline phosphatase activity in early stages of guided bone regeneration. A descriptive histochemical study in humans.

Alkaline phosphatase (ALP) catalyzes the hydrolysis of phosphate esters and it seems to be a prerequisite for normal skeletal mineralization. Also, ALP is the most widely recognized marker of osteoblast phenotypes. By a tissue regenerative technique called Guided Bone Regeneration (GBR), it is possible nowadays to regenerate small bony defects. The aim of the present study was to investigate early events in bone healing and neogenesis by studying histochemically the temporal and local appearance of the marker Alkaline Phosphatase (ALP) in a GBR model system. Nine healthy volunteers (5 males, 4 females, mean age 31.7 years) participated in the experiment. After raising a mucoperiosteal flap from the mandibular second molar to the retromolar area in each volunteer, a hollow titanium test cylinder was placed into a congruent bony bed and the coronal end of the cylinder was closed with an ePTFE-membrane. Then the flap was adapted and sutured to obtain primary wound closure. After 2, 7 and 12 weeks, the regenerated tissue within the cylinders was harvested. Histologically, ALP activity was observed associated with the osteoid seams in the very basal part of the regenerate where new bone trabeculae were in the process of being formed. More coronally, large round cells seemed to secrete an ALP-positive substance since in the center of such cell clusters strong ALP activity located extracellularly was detected. In the present experiment, ALP seemed to have been an early sign of osteoblast secretion of a matrix which subsequently was determined to become osteoid. ALP activity was never seen isolated within connective tissue and away from bone. This is an indication that its source is linked to existing bone. The present study has documented for the first time the appearance of ALP activity in guided bone regenerations in humans. It has revealed that: 1) Osteogenesis in guided bone regeneration is preceded by localized, marked expression of ALP in an organized connective tissue environment. 2) Bone neogenesis is an early event in this experimental setup and may be detected already 2 weeks after wounding. 3) Expression of ALP and subsequent bone neogenesis is originating from and topographically linked to pre-existing bone structures.

Adult↗

[Endoscopic multi-color deglutition study].

BACKGROUND: The complexity of the diagnostic/therapeutic problem in ENT-specific as well as in neurogenic dysphagia requires that test foods be offered in a variety of consistencies (viscosities), at different temperatures, and with various tastes. The swallowing assessment is undertaken with different head and trunk postures, using different swallowing techniques. METHODS: A series of test foods of varied viscosities is prepared with different food colorings. It is given to the patient according to an individually-tailored viscosity plan, but usually in the same (repeatable) color sequence of blue-yellow or blue-yellow-black, an order which offers optimal color contrasts. RESULTS, CONCLUSIONS: During repeated swallowing assessments, the "multicolor technique" is more useful for endoscopic observation of the pharyngolaryngeal route of the food bolus than the "methylene blue swallow". Food coloring is cheap and it changes neither the taste nor the pH of the food.

Deglutition↗

Expression of AhR and ARNT mRNA in cultured human endometrial explants exposed to TCDD.

Endometriosis is a debilitating disease found in 10-15% of reproductive-age women and is characterized by the presence of endometrial tissue outside of the uterus. The present study characterizes the expression of AhR and ARNT mRNA in a human endometrial explant culture model in the absence and presence of TCDD exposure. In a parallel, companion study using this model, TCDD exposure was shown to induce CYP1A1 mRNA, CYP1B1 mRNA, EROD (7-ethoxyresorufin-O-deethylase) activity, and CYP1B1 protein in human endometrial explants. Explants were prepared from specimens obtained at laparoscopy or laparotomy from women undergoing surgery for tubal ligation, endometriosis, or pelvic pain unrelated to endometriosis. These specimens were a subset of the specimens used in the parallel study. The explants were cultured in medium containing 10 nM estradiol (E(2)) or 1 nM estradiol plus 500 nM progesterone (E(2) + P(4)) with or without TCDD (first 24 h). After culture, AhR and ARNT mRNA expression were quantified by RT-PCR. TCDD treatment significantly increased the expression of AhR mRNA, but not ARNT mRNA. The expression of both genes was similar for all individual explants and the ratio of AhR:ARNT mRNA expression across all samples was 1.7 to 1.8. Constitutive AhR mRNA expression was donor age dependent (increasing with age), while ARNT mRNA expression was donor age and tissue phase dependent (increased in older and proliferative phase specimens). Similar to results in the parallel study on expression of CYP1A1 mRNA, CYP1B1 mRNA, EROD activity, and CYP1B1 protein, the presence of endometriosis did not affect the expression of AhR or ARNT mRNA, either constitutively or following TCDD exposure. However, the detection of disease-specific change was limited by small sample size and variability in tissue cycle phase. The human endometrial explant culture model will be useful for future studies of the effects of dioxin-like compounds on human endometrium in relationship to cycle phase, hormonal exposure, and donor age.

Aryl Hydrocarbon Hydroxylases↗

Molecular characterization of tomato 3-dehydroquinate dehydratase-shikimate:NADP oxidoreductase.

Analysis of cDNAs encoding the bifunctional 3-dehydroquinate dehydratase-shikimate:NADP oxidoreductase (DHQase-SORase) from tomato (Lycopersicon esculentum) revealed two classes of cDNAs that differed by 57 bp within the coding regions, but were otherwise identical. Comparison of these cDNA sequences with the sequence of the corresponding single gene unequivocally proved that the primary transcript is differentially spliced, potentially giving rise to two polypeptides that differ by 19 amino acids. Quantitative real-time polymerase chain reaction revealed that the longer transcript constitutes at most 1% to 2% of DHQase-SORase transcripts. Expression of the respective polypeptides in Escherichia coli mutants lacking the DHQase or the SORase activity gave functional complementation only in case of the shorter polypeptide, indicating that skipping of a potential exon is a prerequisite for the production of an enzymatically active protein. The deduced amino acid sequence revealed that the DHQase-SORase is most likely synthesized as a precursor with a very short (13-amino acid) plastid-specific transit peptide. Like other genes encoding enzymes of the prechorismate pathway in tomato, this gene is elicitor-inducible. Tissue-specific expression resembles the patterns obtained for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase 2 and dehydroquinate synthase genes. This work completes our studies of the prechorismate pathway in that cDNAs for all seven enzymes (including isozymes) of the prechorismate pathway from tomato have now been characterized.

3' Untranslated Regions↗

In planta regulation of extension of an endophytic fungus and maintenance of high metabolic rates in its mycelium in the absence of apical extension.

The fungus Neotyphodium lolii is an endophytic symbiont. It grows in the intercellular spaces of the perennial ryegrass Lolium perenne, producing secondary metabolites which enhance the fitness of the association over that of uninfected L. perenne. We report that the average number of hyphal strands in a given section of a leaf remains constant during the life of a leaf, indicating synchrony of leaf and hyphal extension, including cessation of hyphal extension when leaf extension ceases. We used a constitutively expressed reporter gene as an indicator of the mycelium's metabolic activity during and after hyphal extension. Reporter gene activity decreased when the mycelium stopped extending in liquid culture but not in planta. This indicates that in planta endophyte hyphae remain metabolically highly active when extension has ceased and throughout the life of the leaf they are colonizing. The behavior of the fungus in planta indicates the existence of signaling pathways which (i) synchronize the extension of leaf and hypha by regulating hyphal extension, (ii) suppress hyphal branching, and (iii) stop apical extension of fungal hyphae, without reducing the mycelium's metabolic activity. These signals may be crucial for the symbiosis, by allowing the endophyte to switch the focus of its metabolic activity from extension to the production of secondary metabolites.

Ascomycota↗

Liquid chromatographic-tandem mass spectrometric method for the analysis of a neurokinin-1 antagonist and its metabolite using automated solid-phase sample preparation and automated data handling and reporting.

Pharmacokinetic studies play a vital role during the development of new pharmaceutical substances. Data presented demonstrate an accurate, precise and robust assay for a neurokinin-1 receptor antagonist and its metabolite with HPLC-MS-MS. Sample preparation is performed by solid-phase extraction (SPE) in the 96-well plate format. This process is fully automated with a Tecan Genesis pipetting system using its standard robotic manipulator arm (ROMA). All instruments are fully integrated in a study oriented laboratory information system (LIMS) with an Oracle database that communicates bi-directional with the analytical equipment. Finally, the results are reported by push button operation.

Automation↗

Absence of odd-even parity behavior for Kondo resonances in quantum dots.

Zero-bias anomalies in the conductance through quantum dots have recently been identified as Kondo resonances and explained in terms of the Anderson impurity model. The effect requires a degeneracy and it has been proposed that this should occur for odd electron numbers on the dot. In this paper we present data, obtained on a split-gate quantum dot with a small number of electrons, which are in disagreement with this expectation. The mapping of the Anderson model on the quantum dot is discussed in terms of an interacting N electron system demonstrating why this expectation can fail.

Journal Article↗

[Lassa fever].

UNLABELLED: A 22-year-old female German student was admitted with fever of unknown origin for 5 days to the hospital of her hometown immediately after returning from a 7-week journey under simple conditions through 4 West African countries. After exclusion of malaria and typhoid and nonrespondence to antibiosis, she was transferred on the 4th day to the Department of Tropical Medicine in Würzburg. After the clinical assumption of Lassa fever, the virus was confirmed by PCR within 3 hours (Bernhard Nocht Institute, Hamburg) on the 10th day of her illness. The assumption was based on travel history, continuous fever, cough, pharyngitis, thoracic pain, and exclusion of other acute infections. From the beginning, the patient was cared for with barrier nursing and after diagnosis under strict isolation in an intensive care unit reserved for her alone by a team of doctors and nurses specialized in tropical medicine and intensive care. The staff was protected through isolation suits with filters. Monitoring and therapy entailed all methods of intensive care and intravenous administration of ribavirin 16 mg/kg body weight = 900 mg every 6 hours. The patient died on the 14th day of her illness in a volume deficiency shock due to uncontrollable heavy hemorrhage from all organs including the skin, a so-called "leakage syndrome". CONCLUSION: Conclusions are drawn regarding training in tropical medicine, diagnostics of highly contagious infections, intensive care of patients affected with them under isolation, contact tracing, psychological crisis intervention for personnel, media information, care of the infectious corpse and disposal of infectious waste.

Adult↗