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Biomedical subjects

B Schmid

Publications and source records attributed to B Schmid.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Effectiveness and tolerance of standardized willow bark extract in arthrosis patients. Randomized, placebo controlled double-blind study].

OBJECTIVE: To assess the clinical efficacy of a chemically standardized willow bark extract in the treatment of osteoarthritis. METHODS: Willow bark extract, in a dose corresponding to 240 mg salicin/day, was compared to placebo in a 2-week, double-blind, randomized controlled trial. The primary outcome measure was the pain dimension of the WOMAC Osteoarthritis Index. Secondary outcome measures included the stiffness and physical function dimensions of the WOMAC, daily visual analogue scales (VAS) on pain and physical function, and final overall assessment by both patients and investigators. RESULTS: 78 patients (39 willow bark extract, 39 placebo) participated in the trial. A statistically significant difference between active treatment and placebo group was observed in the WOMAC pain dimension (d = 6.5 mm, 95% C.I. = 0.2-12.7 mm, p = 0.047); the WOMAC pain score was reduced by 14% from baseline level after two weeks of active treatment, compared to an increase of 2% in the placebo group. Patient diary VAS confirmed this result, and likewise the final overall assessments showed superiority of willow bark extract over placebo (patients assessment, p = 0.0002; investigators assessment, p = 0.0073). CONCLUSION: Willow bark extract shows a moderate analgesic effect in osteoarthritis.

Activities of Daily Living↗
PubMed2000

Nitroglycerin application during cesarean delivery: plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns.

OBJECTIVE: We sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery. STUDY DESIGN: At the time of the uterine puncture incision, either 0. 25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1, 5, and 10 minutes after birth. RESULTS: Sixty-two patients were included in the pharmacokinetic study. Median maternal plasma levels 1 and 5 minutes after injection of 0.5 mg nitroglycerin were 80 and 3.2 ng/mL, respectively; median maternal plasma levels 1 and 5 minutes after injection of 0.25 mg nitroglycerin were 38 and 1.2 ng/mL, respectively. In the umbilical vein 1 minute after application of 0. 5 mg or 0.25 mg nitroglycerin, the plasma levels were 0.41 and 0.09 ng/mL, respectively, and in the umbilical artery they were 0.03 and 0.008 ng/mL, respectively. Circulatory parameters and Apgar scores in the neonates did not differ significantly from those found in the placebo group. CONCLUSION: The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates.

Adolescent↗
PubMed2000

Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation.

A bone morphogenetic protein (BMP) signaling pathway acts in the establishment of the dorsoventral axis of the vertebrate embryo. Here we demonstrate the genetic requirement for two different Bmp ligand subclass genes for dorsoventral pattern formation of the zebrafish embryo. From the relative efficiencies observed in Bmp ligand rescue experiments, conserved chromosomal synteny, and isolation of the zebrafish bmp7 gene, we determined that the strongly dorsalized snailhouse mutant phenotype is caused by a mutation in the bmp7 gene. We show that the original snailhouse allele is a hypomorphic mutation and we identify a snailhouse/bmp7 null mutant. We demonstrate that the snailhouse/bmp7 null mutant phenotype is identical to the presumptive null mutant phenotype of the strongest dorsalized zebrafish mutant swirl/bmp2b, revealing equivalent genetic roles for these two Bmp ligands. Double mutant snailhouse/bmp7; swirl/bmp2b embryos do not exhibit additional or stronger dorsalized phenotypes, indicating that these Bmp ligands do not function redundantly in early embryonic development. Furthermore, overexpression experiments reveal that Bmp2b and Bmp7 synergize in the ventralization of wild-type embryos through a cell-autonomous mechanism, suggesting that Bmp2b/Bmp7 heterodimers may act in vivo to specify ventral cell fates in the zebrafish embryo.

Amino Acid Sequence↗
PubMed2000

Persistence patterns of Porphyromonas gingivalis, Prevotella intermedia/nigrescens, and Actinobacillus actinomyetemcomitans after mechanical therapy of periodontal disease.

BACKGROUND: The aim of this study was to determine the distribution patterns of Porphyromonas gingivalis, Prevotella intermedia/nigrescens, and Actinobacillus actinomycetemcomitans in periodontitis patients after standard mechanical periodontal therapy, and to determine factors increasing the odds to detect these target organisms in treated sites. METHODS: Eight hundred fifty-two (852) separate subgingival microbial samples were taken from the mesial and distal aspects of every tooth in 17 patients. Target organisms were identified culturally. RESULTS: The 3 microorganisms showed different persistence patterns: P. gingivalis was detected in a high percentage of subjects (59%), but in a low proportion of sites (5.4%). P. intermedia/nigrescens was detected in all subjects except one, and in 40.6% of the tested sites. Only 5 subjects were A. actinomycetemcomitans positive, but 2 of them showed a very high number of positive sites (44% and 75%, respectively). A highly significant relationship was found between a subject's tendency to bleed upon sampling and the number of P. intermedia/nigrescens-positive sites. A significant portion of the variation in frequency of persisting P. gingivalis could be explained by the frequency of persisting pockets deeper than 4 mm. No similar relationship could be established between clinical parameters and A. actinomycetemcomitans. On a site level, the odds of detecting P. gingivalis increased by a factor of 2.47 (P= 0.0001) for every millimeter of residual probing depth; the odds of detecting P. intermedia/nigrescens increased by a factor of 1.84 (P= 0.0001). CONCLUSIONS: If, after standard mechanical periodontal therapy, a large number of sites continue to bleed, one may expect an increased number of sites positive for P. intermedia/ nigrescens. If many deep pockets persist, a greater number of P. gingivalis-positive sites can be expected.

Adult↗
PubMed2000

RAPD variation among and within small and large populations of the rare clonal plant Ranunculus reptans (Ranunculaceae).

In the pre-alpine region of Europe numbers and sizes of populations of the clonal lake shore plant Ranunculus reptans have declined because of the regulation of lake water levels. We investigated genetic variation among and within 17 populations of different size (cover 1-10 000 m) in R. reptans with RAPD (random amplified polymorphic DNA) profiles. We sampled 127 rosettes in 14 populations at Lake Constance and three populations at or near Lake Como. There was significant genetic variation between plants from the two lake regions (5.9%, analysis of molecular variance [AMOVA], P < 0.001), among populations within lake regions (20.4%, P < 0.001), and within populations (73.7%, P < 0.001). Under the assumptions of Wright's island model the variation among populations corresponds to a gene flow of N(e)m = 0.70. Within the 14 Lake Constance populations we detected significant genetic variation among subpopulations separated by only a few metres (4.0% of the within-population variation; P < 0.05). Molecular variance was 24% smaller in small populations covering <100 m area than in larger ones (P < 0.03), indicating that samples from large populations were genetically more variable than samples representing comparable areas of smaller populations. We conclude that gene flow among populations is very limited and that genetic drift has caused reduced genetic variability of smaller populations. Conservation of genetic variability in R. reptans requires persistence of large and also of small populations (because of population differentiation), and it could be enhanced by increasing the size of small populations (to counter genetic drift).

Journal Article↗
PubMed2000

Costs of plasticity in foraging characteristics of the clonal plant Ranunculus reptans.

In clonal plants, evolution of plastic foraging by increased lengths of leaves and internodes under unfavourable conditions may be constrained by costs and limits of plasticity. We studied costs and limits of plasticity in foraging characteristics in 102 genotypes of the stoloniferous herb Ranunculus reptans. We grew three replicates of each genotype with and three without competition by the naturally co-occuring grass Agrostis stolonifera. We used regression and correlation analyses to investigate potential costs of plasticity in lengths of leaves and stolon internodes, developmental instability costs of these traits, and a developmental range limit of these traits. We used randomization procedures to control for spurious correlations between parameters calculated from the same data. Under competition the number of rosettes, rooted rosettes, and flowers was 58%, 40%, and 61% lower, respectively, than in the absence of competition. Under competition lengths of leaves and stolon internodes were 14% and 6% smaller, respectively, than in the absence of competition. We detected significant costs of plasticity in stolon internode length in the presence of competition when fitness was measured in terms of the number of rosettes and the number of flowers (selection gradients against plasticity were 0.250 and 0.214, respectively). Within-environment variation (SD) in both foraging traits was not positively correlated with the corresponding plasticity, which indicates that there were no developmental instability costs. More plastic genotypes did not have less extreme trait values than less plastic genotypes for both foraging traits, which indicates that there was no developmental range limit. We conclude that in R. reptans costs of plasticity more strongly constrain evolution of foraging in the horizontal plane (i.e., stolon internode length) than in the vertical plane (i.e., leaf length).

Adaptation, Physiological↗
PubMed1999

Plant diversity and productivity experiments in european grasslands

At eight European field sites, the impact of loss of plant diversity on primary productivity was simulated by synthesizing grassland communities with different numbers of plant species. Results differed in detail at each location, but there was an overall log-linear reduction of average aboveground biomass with loss of species. For a given number of species, communities with fewer functional groups were less productive. These diversity effects occurred along with differences associated with species composition and geographic location. Niche complementarity and positive species interactions appear to play a role in generating diversity-productivity relationships within sites in addition to sampling from the species pool.

Journal Article↗
PubMed1999

Interaction between the endophytic fungus Epichloe bromicola and the grass bromus erectus: effects of endophyte infection, fungal concentration and environment on grass growth and flowering

Epichloe bromicola is an endophytic fungal species that systemically and perennially colonizes intercellular spaces of leaf blades, leaf sheaths and culms of Bromus grass species. E. bromicola causes choke disease in B. erectus, suppressing maturation of most, if not all, host inflorescences. In an investigation of the interaction between fungus and host, we used a quantitative polymerase chain reaction technique to estimate the amount of fungal DNA, and thereby fungal concentration, in host plants. Fungal concentration was directly correlated with vegetative vigour of the plant, as measured by longest leaf length, number of tillers and vegetative above-ground biomass, suggesting that, during vegetative growth, the endophytic fungus is most beneficial for the plant when present in high concentrations. In contrast, the reproduction of the plant, as measured by the number of functional inflorescences, was inversely correlated with fungal concentration: the majority of infected plants, and all that were associated with high concentrations of fungi, were diseased. Thus, the benefit of endophyte infection for the plant is coupled with the disadvantages of infertility. Fungal concentration was shown to be at least in part genetically determined because fungal concentration differed significantly in different plant-endophyte genotype combinations (symbiotum). In a field experiment with normal and CO2-enriched environments, elevated CO2 levels favoured fungal reproductive vigour over host reproductive vigour, suggesting that these plant endophytes would be at a selective advantage in a corresponding environmental-change scenario. We conclude that a dynamic and complex relationship between fungal endophyte infection, fungal concentration, genotype and environment affects growth and fecundity of B. erectus and should contribute to the evolution of these plant-fungal interactions.

Journal Article↗
PubMed1998

Ventral and lateral regions of the zebrafish gastrula, including the neural crest progenitors, are established by a bmp2b/swirl pathway of genes.

A bone morphogenetic protein (BMP) signaling pathway is implicated in dorsoventral patterning in Xenopus. Here we show that three genes in the zebrafish, swirl, snailhouse, and somitabun, function as critical components within a BMP pathway to pattern ventral regions of the embryo. The dorsalized mutant phenotypes of these genes can be rescued by overexpression of bmp4, bmp2b, an activated BMP type I receptor, and the downstream functioning Smad1 gene. Consistent with a function as a BMP ligand, swirl functions cell nonautonomously to specify ventral cell fates. Chromosomal mapping of swirl and cDNA sequence analysis demonstrate that swirl is a mutation in the zebrafish bmp2b gene. Interestingly, our analysis suggests that the previously described nonneural/neural ectodermal interaction specifying the neural crest occurs through a patterning function of swirl/bmp2b during gastrulation. We observe a loss in neural crest progenitors in swirl/bmp2b mutant embryos, while somitabun mutants display an opposite, dramatic expansion of the prospective neural crest. Examination of dorsally and ventrally restricted markers during gastrulation reveals a successive reduction and reciprocal expansion in nonneural and neural ectoderm, respectively, in snailhouse, somitabun, and swirl mutant embryos, with swirl/bmp2b mutants exhibiting almost no nonneural ectoderm. Based on the alterations in tissue-specific gene expression, we propose a model whereby swirl/bmp2b acts as a morphogen to specify different cell types along the dorsoventral axis.

Animals↗
PubMed1998

Synthesis and antitumor activity of [1,2-bis(4-fluorophenyl)ethylenediamine][dicarboxylato]platinum(II) complexes.

The synthesis of the diastereomeric [1,2-bis(4-fluorophenyl)-ethylenediamine][dicarboxylato]platinum(I I) complexes, rac- and meso-4F-Pt(X) [X: oxalato (Ox), malonato (Mal), hydroxymalonato (OHMal), phenylmalonato (PhMal), tetrahydro-4H-pyran-4,4-dicarboxylato (Thpdc)], the evaluation of their structure, water solubility, resistance against attack by nucleophiles, and growth inhibiting properties on the human MCF-7 breast cancer cell line are described [parent compounds: rac-4F-Pt(CBDC) and meso-4F-Pt(CBDC); reference complexes: carboplatin, cisplatin, rac- and meso-4F-PtCl2]. The most active 4F-Pt(X) complexes, rac-4F-Pt(Mal), rac-4F-Pt(OHMal) and rac-4F-Pt(Thpdc), equal the parent compound rac-4F-Pt(CBDC) as well as cisplatin and surpass carboplatin in their effect on the MCF-7 breast cancer cell line. Their water solubility, which is of importance for an application in the cancer chemotherapy, is higher than that of rac-4F-Pt(CBDC), especially in the case of rac-4F-Pt(OHMal) and rac-4F-Pt(Thpdc). In comparison to the dichloroplatinum(II) analogue (4F-PtCl2) the stability of the three compounds in the presence of the strong nucleophile iodide is markedly enhanced, which means a reduction of the protein bound drug fraction in the blood and tissue compartments accompanied by an increase of the active, free drug level. The found physiochemical properties of these compounds meet the requirements for the transferability of their promising breast cancer inhibiting effects detected in cell culture experiments to in vivo conditions.

Antineoplastic Agents↗
PubMed1998

Porin mutants with new channel properties.

The general diffusion porin from Rhodopseudomonas blastica was produced in large amounts in Escherichia coli inclusion bodies and (re)natured to the exact native structure. Here, we report on 13 mutants at the pore eyelet giving rise to new diffusion properties as measured in planar lipid bilayer experiments. The crystal structures of seven of these mutants were established. The effects of charge-modifying mutations at the pore eyelet are consistent with the known selectivity for cations. Deletions of 16 and 27 residues of the constriction loop L3 resulted in labile trimers and pores. The reduction of the eyelet cross section by introducing tryptophans gave rise to a closely correlated decrease of the conductivities. A mutant with six newly introduced tryptophans in the eyelet closed its pore in a defined manner within seconds under a voltage of 20 mV, suggesting the existence of two states. The results indicate that the pore can be engineered in a rational manner.

Amino Acid Substitution↗
PubMed1998

Ascaris suum: protein phosphotyrosine phosphatases in oocytes and developing stages.

Protein tyrosine phosphatases were analyzed in oocytes of Ascaris suum. Phosphatases dephosphorylating modified acidic lysozyme were present in high-molecular-weight form (M(r) > 600,000) and as a 50- to 55-kDa protein in the soluble fraction. The low-molecular-weight form of the phosphatase cross-reacted with an antiserum raised against human T-cell protein tyrosine phosphatase and was not distinguishable from the 50- to 55-kDa protein tyrosine phosphatase previously described in the muscular layer of the adult worms (B. Schmid et al. 1996, Molecular and Biochemical Parasitology 77, 183-192). The low-molecular-weight form was also present on immunoblots of high-molecular-weight protein tyrosine phosphatase preparations after denaturing electrophoresis. The same or a similar form of the tyrosine phosphatase was also found in detergent extracts from the pelletal fraction. In addition, another tyrosine phosphatase of 180 kDa molecular mass that dephosphorylated myelin basic protein was also found in extracts from the soluble compartment as well as in detergent extracts from the pelletal fraction. It showed no cross-reactivity with antisera raised against soluble mammalian phosphatases and was resistant to inhibition by vanadate. While the activities of the myelin basic protein-dephosphorylating protein phosphatase remained fairly constant during early development of the oocytes, the activity of the enzyme dephosphorylating modified lysozyme in the pelletal fraction decreased to less than 10% of the initial activity between days 3 and 28 of incubation. Immunocytochemical studies of unfertilized and developing Ascaris eggs revealed association of protein tyrosine kinase and protein tyrosine phosphatase with the egg shell, in addition to their presence in the neighborhood of mitochondria. The amount of enzyme changed with the stage of development. In the larval stage (21 days) protein tyrosine kinase had increased in the chitin layer of the shell and in the nuclei while the relative amount of tyrosine phosphatase decreased in accordance with the biochemical data.

Animals↗
PubMed1998

Stability and cellular studies of [rac-1,2-bis(4-fluorophenyl)-ethylenediamine][cyclobutane-1,1- dicarboxylato]platinum(II), a novel, highly active carboplatin derivative.

The synthesis of the diastereomeric [1,2-bis(4-fluorophenyl)ethylenediamine][cyclobutane-1, 1-dicarboxylato]platinum(II) complexes, rac- and meso-4F-Pt(CBDC), the evaluation of their structures, their tumor-inhibiting properties and their stability in physiological environment are described (reference complexes: the dichloro- and sulfatoplatinum(II) analogues, carboplatin and cisplatin). The most interesting diastereomer, rac-4F-Pt(CBDC), equals cisplatin and surpasses carboplatin in its effect on human breast cancer cell lines (MCF-7 and MDA-MB-231). Rac-4F-Pt(CBDC) is largely insensitive against attack of nucleophiles e.g. Cl-, a prerequisite for sufficient stability in vivo and for fewer side effects. In accordance with this, in vitro studies on the binding of rac-4F-Pt(CBDC) to albumin, the main plasma protein, show that the free, non-protein-bound fraction is relatively high, coming close to that of carboplatin. These properties are of importance for the transferability of the promising effects found in the cell culture experiments to in vivo conditions. The distinctly better anti-breast cancer activity of rac-4F-Pt(CBDC) than of carboplatin has been attributed to its ability to accumulate in the tumor cells. The human ovarian cancer cell line NIH-OVCAR-3 is also strongly inhibited by rac-4F-Pt(CBDC).

Breast Neoplasms↗
PubMed1998

Use of amoxicillin-clavulanate and resistance in Escherichia coli over a 4-year period.

OBJECTIVE: To reduce the use of amoxicillin-clavulanate after high-resistance rates in Escherichia coli were detected. DESIGN: Intervention study; the interventions were introduced successively over a 4-year period while closely monitoring the resistance patterns. SETTING: A 260-bed acute-care hospital in Switzerland. INTERVENTIONS: Introduction of therapeutic guidelines for specific departments or indications, which proposed alternative antibiotics to amoxicillin-clavulanate. The perioperative prophylactic use of amoxicillin-clavulanate was eliminated completely. RESULTS: The absolute amount of amoxicillin-clavulanate consumed decreased by 23%, from 24.8 g per 100 patient days in 1992 to 18.5 g per 100 patient days in 1995. The number of courses, a parameter that takes the prophylactic use into account, decreased by 62% from 2.3 per 100 patient days in 1992 to 0.9 per 100 patient days in 1995. The percentage of sensitive strains increased from 54.9% (n=512) in 1992 and 54.0% (n=506) in 1993 to 72.1% (n=546) in 1994 and 83.1% (n=668) in 1995. No major changes were detected for other antimicrobials, such as cotrimoxazole, tetracycline, or cefuroxime, used in this 4-year period. CONCLUSIONS: A decrease in the use of amoxicillin-clavulanate was followed by an increase in susceptibility of E coli to it. It was not possible to prove a causative relationship. Only a temporal association was discovered. The reduction of the use of amoxicillin-clavulanate was achieved through the implementation of treatment guidelines, facilitated through a close collaboration among the clinical pharmacists, the infection control practitioner, the microbiology laboratory, and the physicians in charge of the respective departments.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1997

A three-dimensional working model for a guide RNA from Trypanosoma brucei.

RNA editing in protozoan parasites is a mitochondrial RNA processing reaction in which exclusively uridylate residues are inserted into, and less frequently deleted from, pre-mRNAs. Molecules central to the process are so-called guide RNAs (gRNAs) which function as templates in the reaction. For a detailed molecular understanding of the mechanism of the editing process knowledge of structural features of gRNAs will be essential. Here we report on a computer-assisted molecular modelling approach to construct the first three-dimensional gRNA model for gND7-506, a ND7-specific gRNA from Trypanosoma brucei. The modelling process relied on chemical modification and enzymatic probing data and was validated by in vitro mutagenesis experiments. The model predicts a reasonably compact structure, where two stem/loop secondary structure elements are brought into close proximity by a triple A tertiary interaction, forming a core element within the centre of the molecule. The model further suggests that the surface of the gRNA is primarily made up of the sugar-phoshate backbone. On the basis of the model, footprinting experiments of gND7-506 in a complex with the gRNA binding protein gBP21 could successfully be interpreted and provide a first picture for the assembly of gRNAs within a ribonucleoprotein complex.

Animals↗
PubMed1997

Trypanosoma brucei gBP21. An arginine-rich mitochondrial protein that binds to guide RNA with high affinity.

RNA editing in Trypanosoma brucei is a mitochondrial RNA processing reaction that results in the insertion and deletion of uridylate residues into otherwise untranslatable mRNAs. The process is directed by guide RNAs which function to specify the edited sequence. RNA editing in vitro requires mitochondrial protein extracts and guide RNAs have been identified as part of high molecular weight ribonucleoprotein complexes. Within the complexes, the RNAs are in close contact with several mitochondrial proteins and here we describe the isolation and cloning of a gRNA-interacting polypeptide from Trypanosoma brucei. The protein was named gBP21 for guide RNA-binding protein of 21 kDa. gBP21 shows no homology to proteins in other organisms, it is arginine-rich and binds to gRNA molecules with a dissociation constant in the nanomolar range. The protein does not discriminate for differences in the primary structures of gRNAs and thus likely binds to higher order structural features common to all gRNA molecules. gBP21 binding does not perturb the overall structure of gRNAs but the gRNA/gBP21 ribonucleoprotein complex is more stable than naked guide RNAs. Although the protein is arginine-rich, the free amino acid or an arginine-rich peptide were not able to inhibit the association to the RNAs. In contrast, the gRNA-gBP21 complex formation was sensitive to potassium and ammonium cations, thus indicating a contribution of ionic contacts to the binding.

Amino Acid Sequence↗