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Biomedical subjects

W Fuchs

Publications and source records attributed to W Fuchs.

At least 19 recordsLinked to original sources
PubMed2006

A novel processing method for injection-molded polyether-urethane scaffolds. Part 1: processing.

A large-scale scaffold processing method with injection molding has been successfully developed. Water was used as afoaming agent for the new technique. NaCl was used as a porogen to achieve an open-cell structure. Organic solvents, which are common foaming agents for polyurethane, where not used. Toxic remains in the polymer were therefore prevented. Pore size and porosity was adjustable through process parameters. A parameter study showed that an increase in injection pressure, plasticize speed, cylinder, and mold temperature raised the mean pore diameter. The porosity also could be mended by the cylinder and mold temperature, in addition to NaCl concentration. It was possible to produce scaffolds with a porosity of 64 +/- 3%, a pore size distribution from 30-450 microm, and a mean pore diameter of 270 +/- 90 microm. The interconnective pores were found to lie between 5 and 58 microm.

Biocompatible Materials↗
PubMed2005

[Rapidity of pain relief, medication requirement and patient satisfaction with reflux treatment in the physician's office].

Treatment of gastroesophageal reflux disease (GERD) with proton pump inhibitors was investigated in three controlled prospective, randomized open studies. Lansoprazole, omeprazole MUPS and esomeprazole were compared under doctor's office conditions. The outcomes of interest were the rapidity of pain relief achieved with a single dose, effectiveness and patient satisfaction with on demand therapy. In the first study, 180 patients with chronic and prolonged episodes of reflux were investigated. Time to pain relief following a single dose was 1.1 +/- 0.8 hours with 30 mg lansoprazole, 3.0 +/- 2.5 hours with 20 mgomeprazole MUPS and 2.1 +/- 1.2 hours with 40 mg esomeprazole. Studies 2 and 3 were designed as cross-over studies intended to investigate drug consumption. In study 2, the amount of lansoprazole consumed was approximately 50% less than that of omeprazole, and this translated to 81% patient satisfaction with lansoprazole compared with only 9.5% for omeprazole. In study 3 comparing lansoprazole and esomeprazole, consumption of the former was 85% that of the latter. 58% of the patients opted to continuetreatment with lansoprazole, compared with only 25% in the case of esomeprazole. The appreciably greater patient satisfaction with lansoprazole was due tothe faster pain relief achieved with this drug.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Influence of operational conditions on the performance of a mesh filter activated sludge process.

Recently, a new type of wastewater treatment system became the focus of scientific research, the mesh filter activated sludge system. It is a modification of the membrane bioreactor where a membrane filtration process serves to separate the sludge from the purified effluent. The difference is that a mesh filter is used instead of the membrane. Due to the much larger pore size of the mesh, the effluent is not of the same excellent quality as with membrane bioreactors. Nevertheless, it still resembles the quality of the now most widely used standard treatment system, where settling tanks are used to retain the activated sludge. At the same time, the new system features all the other advantages of membrane bioreactors including elevated sludge concentrations resulting in decreased volumina of basins and complete substitution of the settling tank. Therefore, this process presents a potential future alternative where a small footprint of the plant is required. However, so far only a few preliminary studies on this innovative process type have been done. In this paper, the effects of suspended solids concentration, flux rate as well as aeration rate on the effluent quality are discussed. Furthermore, the characteristic of the sludge floc was identified as a factor of vital importance. Therefore, another influencing parameter, the food to microorganism (F/M) ratio, which is known to have a significant effect on floc characteristics, was studied. The main result demonstrated that the process was very effective under most of the operation conditions. The suspended solids concentration in the effluent was below 12 mg l(-1), the average COD in the effluent was between 24 and 45 mg l(-1) and the BOD(5) was lower than 5 mg l(-1). High flux rates of up to 150 l m(-2)h(-1) were also achieved.

Bioreactors↗
PubMed2004

Effect of ozone, chlorine and hydrogen peroxide on the elimination of colour in treated textile wastewater by MBR.

In treating textile wastewater, the application of membrane bioreactor (MBR) technology showed high efficiency in COD and BOD5 removal. However, insufficient colour removal was achieved for possible reuse. The aim of the work presented in this paper was to test the performance of chemical advanced oxidation on the elimination of the colour downstream of an MBR. To improve the quality of the membrane bioreactor effluent three different oxidation treatments were tested at lab-scale: ozonation, chlorination and hydrogen peroxide oxidation. Colour, COD and BOD5 were controlled in order to assess the effectiveness of each process. For chlorination, even with 250 mg/L (active chlorine) only 80% colour removal (SACin = 14; SACout = 2.8) was achieved which is considered unsatisfactory. For hydrogen peroxide, the colour removal was even poorer; it was just 10% at a concentration of 250 mg/L. In contrast, good results were obtained by ozonation. By using only 38 mg/L within 20 minutes, it was possible to achieve the reuse recommendation with a satisfactory colour removal of 93% (SACin = 14; SACout = 0.98). The results showed that ozonation was the most promising method.

Bioreactors↗
PubMed2003

Helicobacter pylori eradication is beneficial in the treatment of functional dyspepsia.

AIM: To assess whether the eradication of Helicobacter pylori leads to long-term relief of symptoms in functional dyspepsia. METHODS: Eight hundred patients with functional dyspepsia were randomized to receive double-blind treatment with twice-daily 30 mg lansoprazole, 1000 mg amoxicillin and 500 mg clarithromycin for 7 days (L30AC), twice-daily 15 mg lansoprazole, 1000 mg amoxicillin and 500 mg clarithromycin for 7 days (L15AC), or once-daily 15 mg lansoprazole for 14 days (LP). Dyspepsia and reflux symptoms were monitored for 12 months. RESULTS: In intention-to-treat analysis, the non-ulcer dyspepsia sum score showed a statistically significant benefit in terms of symptom relief in the L30AC group (P = 0.0068) compared with the LP group, but there was no significant difference between the L15AC and LP groups (P = 0.2). When all patients in the two eradication therapy arms were considered together, successful eradication had a significant benefit with regard to the complete absence of symptoms (P < 0.04). H. pylori eradication did not lead to an increase in reflux symptoms. CONCLUSION: This study suggests that H. pylori infection causes dyspeptic symptoms in a subset of patients with functional dyspepsia, and that these patients may obtain long-term symptomatic benefit following H. pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Anaerobic treatment of wastewater with high organic content using a stirred tank reactor coupled with a membrane filtration unit.

Using a cross-flow membrane bioreactor, high anaerobic conversion rates of three different types of wastewater with varying organic content were achieved. Loading rates obtained were as follows: 20 g CODL(-1) x d(-1) for artificial wastewater, approximately 8 g CODL(-1) x d(-1) from vegetable processing industry (sauerkraut brine) and 6-8 g CODL(-1) x d(-1) for wastewater from an animal slaughterhouse. At stable conditions, COD-removal rates in all three wastewaters were higher than 90%. Methane yields from the treatment of artificial wastewater, sauerkraut brine, and animal slaughterhouse wastewater were in the range of 0.17-0.30, 0.20-0.34, and 0.12-0.32 L(n) x g(-1) COD(-1) fed, respectively. The complete retention of biomass and suspended solids is a unique feature of this treatment process, which combines a high loading capacity and at the same time, high COD removal rates even for complex wastewater containing high concentrations of particulate matter.

Abattoirs↗
PubMed2001

Protection of chickens from lethal avian influenza A virus infection by live-virus vaccination with infectious laryngotracheitis virus recombinants expressing the hemagglutinin (H5) gene.

The H5 hemagglutinin (HA) gene of a highly pathogenic avian influenza virus (AIV) isolate (A/chicken/Italy/8/98) was cloned and sequenced, and inserted at the non-essential UL50 (dUTPase) gene locus of a virulent strain of infectious laryngotracheitis virus (ILTV). Northern and Western blot analyses of the obtained ILTV recombinants demonstrated stable expression of the HA gene under control of the human cytomegalovirus immediate-early gene promoter. In vitro replication of the HA-expressing ILTV mutants was not affected, and infection of chickens revealed a reduced but still considerable virulence, similar to that of a UL50 gene deletion mutant without foreign gene insertion. The immunized animals produced specific antibodies against ILTV and AIV HA, and were protected against challenge infections with either virulent ILTV, or two different highly pathogenic AIV strains (A/chicken/Italy/8/98, A/chicken/Scotland/59). After challenge, no ILTV could be reisolated from protected animals, and shedding of AIV was considerably reduced. Thus, although attenuation remains to be improved, genetically engineered ILTV live-virus vaccines might be used as vectors to protect chickens also against other pathogens.

Animals↗
PubMed2001

Egress of alphaherpesviruses: comparative ultrastructural study.

Egress of four important alphaherpesviruses, equine herpesvirus 1 (EHV-1), herpes simplex virus type 1 (HSV-1), infectious laryngotracheitis virus (ILTV), and pseudorabies virus (PrV), was investigated by electron microscopy of infected cell lines of different origins. In all virus-cell systems analyzed, similar observations were made concerning the different stages of virion morphogenesis. After intranuclear assembly, nucleocapsids bud at the inner leaflet of the nuclear membrane, resulting in enveloped particles in the perinuclear space that contain a sharply bordered rim of tegument and a smooth envelope surface. Egress from the perinuclear cisterna primarily occurs by fusion of the primary envelope with the outer leaflet of the nuclear membrane, which has been visualized for HSV-1 and EHV-1 for the first time. The resulting intracytoplasmic naked nucleocapsids are enveloped at membranes of the trans-Golgi network (TGN), as shown by immunogold labeling with a TGN-specific antiserum. Virions containing their final envelope differ in morphology from particles within the perinuclear cisterna by visible surface projections and a diffuse tegument. Particularly striking was the addition of a large amount of tegument material to ILTV capsids in the cytoplasm. Extracellular virions were morphologically identical to virions within Golgi-derived vesicles, but distinct from virions in the perinuclear space. Studies with gB- and gH-deleted PrV mutants indicated that these two glycoproteins, which are essential for virus entry and direct cell-to-cell spread, are dispensable for egress. Taken together, our studies indicate that the deenvelopment-reenvelopment process of herpesvirus maturation also occurs in EHV-1, HSV-1, and ILTV and that membrane fusion processes occurring during egress are substantially different from those during entry and direct viral cell-to-cell spread.

Alphaherpesvirinae↗
PubMed2000

A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: high-resolution mapping and genomic structure.

We have recently mapped the genetic defect underlying pseudoxanthoma elasticum (PXE), an inherited disorder characterized by progressive calcification of elastic fibers in skin, eye, and cardiovascular system, to chromosome 16p 13.1. Here we report further data on the fine-mapping and genomic structure of this locus. Haplotype analysis of informative PXE families narrowed the locus to an interval of less than 500 kb located between markers D16B9621 and D16S764. Three overlapping YAC clones were found to cover this region through YAC-STS content mapping. An overlapping BAC contig was then constructed to cover this interval and the surrounding region. About 80% of this chromosomal region has been fully sequenced using the BAC shotgun technique. Gene content and sequence analysis predicted four genes (MRP1, MRP6, PM5, and a novel transcript) and two pseudogenes (ARA and PKDI) within this interval. By screening a somatic cell hybrid panel we were able to precision-map the breakpoint of Cy185 and the starting point of a chromosomal duplication within 20 kb of BAC A962B4. The present data further refine the localization of PXE, provide additional physical cloning resources, and will aid in the eventual identification of the genetic defect causing PXE.

Adult↗
PubMed2000

Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum.

We recently published the precise chromosomal localization on chromosome 16p13.1 of the genetic defect underlying pseudoxanthoma elasticum (PXE), an inherited disorder characterized by progressive calcification of elastic fibers in skin, eye, and the cardiovascular system. Here we report the identification of mutations in the gene encoding the transmembrane transporter protein, ABC-C6 (also known as MRP-6), one of the four genes located in the region of linkage, as cause of the disease. Sequence analysis in four independent consanguineous families from Switzerland, Mexico, and South Africa and in one non-consanguineous family from the United States demonstrated several different mis-sense mutations to cosegregate with the disease phenotype. These findings are consistent with the conclusion that PXE is a recessive disorder that displays allelic heterogeneity, which may explain the considerable phenotypic variance characteristic of the disorder.

ATP-Binding Cassette Transporters↗
PubMed2000

Initial potency of lansoprazole and omeprazole tablets on pentagastrin-stimulated gastric acid secretion-a placebo-controlled study in healthy volunteers.

BACKGROUND: The new tablet formulation of omeprazole (Losec MUPS), is thought to have a stronger acid inhibition than the previously marketed capsules. METHODS: The effects of the proton pump inhibitors lansoprazole and omeprazole tablets on pentagastrin-stimulated acid secretion were compared in Helicobacter pylori-negative healthy male volunteers (n=12). The study was placebo-controlled, crossover matched and double-blind for lansoprazole (Agopton) and placebo, and single-blind for omeprazole tablets. Gastric acid response to sub-maximal pentagastrin-stimulation (0.6 microg. h/kg b.w.) was determined from 12.5 to 14.5 h after the first and second dose of the test drugs. RESULTS: Lansoprazole 15 mg and 30 mg as well as omeprazole 20 mg tablets caused a marked decrease in gastric acid secretion, showing equipotency for 15 mg lansoprazole and 20 mg omeprazole tablets. Their efficacy, however, was lower than 30 mg lansoprazole. In addition, the inter-individual variation after omeprazole tablets was higher than following lansoprazole. Neither 7.5 mg lansoprazole nor 10 mg omeprazole tablets were clearly different from placebo on the first 2 days. The drugs were well-tolerated. No clinically relevant influence was found on either laboratory screen or cardiovascular parameters. CONCLUSION: Lansoprazole 15-30 mg shows a stronger acid inhibition and a lower inter-individual variability than the new omeprazole 20 mg tablets on days 1 and 2 of dosing.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

The non-essential UL50 gene of avian infectious laryngotracheitis virus encodes a functional dUTPase which is not a virulence factor.

The DNA sequence of the infectious laryngotracheitis virus (ILTV) UL50, UL51 and UL52 gene homologues was determined. Although the deduced UL50 protein lacks the first of five conserved domains of the corresponding proteins of mammalian alphaherpesviruses, the ILTV gene product was also shown to possess dUTPase activity. The generation of UL50-negative ILTV mutants was facilitated by recombination plasmids encoding green fluorescent protein (GFP), and expression constructs of predicted transactivator proteins of ILTV (alphaTIF, ICP4) were successfully used to increase the infectivity of viral genomic DNA. A GFP-expressing UL50-deletion mutant of ILTV showed reduced cell-to-cell spread in vitro, and was attenuated in vivo. A similar deletion mutant without the foreign gene, however, propagated like wild-type ILTV in cell culture and was pathogenic in chickens. We conclude that the viral dUTPase is not required for efficient replication of ILTV in the respiratory tract of infected animals. The replication defect of the GFP-expressing ILTV recombinant is most likely caused by toxic effects of the reporter gene product, since spontaneously occurring inactivation mutants exhibited wild-type-like growth.

Amino Acid Sequence↗
PubMed2000

Characterization of the replication origin (Ori(S)) and adjoining parts of the inverted repeat sequences of the pseudorabies virus genome.

The DNA sequence of a 2.4 kbp fragment located in the internal and terminal inverted repeat sequences of the pseudorabies virus genome determined in this study closes a gap between the previously described genes for the ICP4 and ICP22 homologues. The novel sequence contains no conserved herpesvirus open reading frames. Northern blot and cDNA analyses revealed a viral immediate-early transcript of 1.8 kb, which is spliced by the removal of two small introns close to its 5' end and which presumably represents the mRNA of the downstream open reading frame encoding the ICP22 homologue. Upstream of the transcribed region, an imperfect set of three directly repeated sequences was identified. Each of them contains a complementary pair of the alphaherpesvirus origin-binding protein recognition motif GTTCGCAC, spaced by AT-rich sequences. In vitro studies confirmed that the DNA fragment analysed includes a functional origin of viral DNA replication.

Animals↗
PubMed2000

Pseudorabies virus glycoprotein K requires the UL20 gene product for processing.

Glycoprotein K (gK) of pseudorabies virus (PrV) has recently been identified as a virion component which is dispensable for viral entry but required for direct cell-to-cell spread. Electron microscopic data suggested a possible function of gK in virus egress by preventing immediate fusion of released virus particles with the plasma membrane (B. G. Klupp, J. Baumeister, P. Dietz, H. Granzow, and T. C. Mettenleiter, J. Virol. 72:1949-1958, 1998). For more detailed analysis, a PrV mutant with a deletion of the UL53 (gK) open reading frame (ORF) from codons 48 to 275 was constructed, and the protein was analyzed with two monoclonal antibodies directed against PrV gK. The salient findings of this report are as follows. (i) From the PrV UL53 ORF, a functional gK is translated only from the first in-frame methionine. From the second in-frame methionine, a nonfunctional product is expressed which is not incorporated into virions. (ii) When constitutively expressed in a stable cell line without other viral proteins, gK is only incompletely processed. After superinfection with gK-deletion mutants, proper processing is restored and mature gK is incorporated into virions. (iii) The UL20 gene product is specifically required for processing of gK. gK is not correctly processed in a UL20 deletion mutant of PrV, and superinfection of gK-expressing cells with PrV-UL20(-) does not restore processing. However, all other known structural viral glycoproteins appear to be processed normally in PrV-UL20(-)-infected cells. (iv) Coexpression of gK and UL20 restored gK processing at least partially. Thus, our data show that the UL20 gene product is required for proper processing of PrV gK.

Animals↗
PubMed2000

Reconstitution of Marek's disease virus serotype 1 (MDV-1) from DNA cloned as a bacterial artificial chromosome and characterization of a glycoprotein B-negative MDV-1 mutant.

The complete genome of Marek's disease virus serotype 1 (MDV-1) strain 584Ap80C was cloned in Escherichia coli as a bacterial artificial chromosome (BAC). BAC vector sequences were introduced into the U(S)2 locus of the MDV-1 genome by homologous recombination. Viral DNA containing the BAC vector was used to transform Escherichia coli strain DH10B, and several colonies harboring the complete MDV-1 genome as an F plasmid (MDV-1 BACs) were identified. DNA from various MDV-1 BACs was transfected into chicken embryo fibroblasts, and from 3 days after transfection, infectious MDV-1 was obtained. Growth of MDV-1 recovered from BACs was indistinguishable from that of the parental virus, as assessed by plaque formation and determination of growth curves. In one of the MDV-1 BAC clones, sequences encoding glycoprotein B (gB) were deleted by one-step mutagenesis using a linear DNA fragment amplified by PCR. Mutant MDV-1 recovered after transfection of BAC DNA that harbored a 2.0-kbp deletion of the 2.6-kbp gB gene were able to grow and induce MDV-1-specific plaques only on cells providing MDV-1 gB in trans. The gB-negative virus reported here represents the first MDV-1 mutant with a deletion of an essential gene and demonstrates the power and usefulness of BACs to analyze genes and gene products in slowly growing and strictly cell-associated herpesviruses.

Animals↗
PubMed2000

The pharmacological potency of various AT(1) antagonists assessed by Schild regression technique in man.

RATIONALE: A quantitative technique was used to compare the pharmacological potency in healthy volunteers of angiotensin II receptor antagonists (AIIA): candesartan cilexetil, losartan, irbesartan, valsartan, and telmisartan. METHODS: In a randomised, double-blind, parallel-group (4x12 subjects) study, single oral doses of candesartan cilexetil 4, 8 and 16 mg, losartan potassium 25, 50 and 100 mg, valsartan 40, 80 and 160 mg, and irbesartan 75, 150 and 300 mg were administered on three consecutive days. Telmisartan 20, 40 and 80 mg was similarly evaluated in 12 volunteers in an open amendment. Angiotensin II (Ang II) antagonistic effects were determined in vivo from rightward shifts in Ang II dose-response curves for diastolic blood pressure (BP) and dose ratios were calculated. Apparent K(i)-doses, i.e. doses (in mg) required to induce a two-fold shift in Ang II dose-response curves (equivalent to approx. 50% blockade of receptors) were determined, using Schild regression analysis. RESULTS: All treatments dose-dependently attenuated increases in diastolic BP induced by infusion of exogenous Ang II. Candesartan cilexetil appeared to have a more pronounced increase in effect following cumulative dosing. At 24 hours, apparent K(i)-doses were: candesartan cilexetil 6 mg, irbesartan 123 mg, valsartan 93.5 mg, and telmisartan 54 mg. It was not possible to determine an apparent K(i)-dose for losartan at 24 hours. CONCLUSION: Consistent with results from experimental pharmacology, candesartan cilexetil displayed the highest pharmacological potency (i.e. antagonistic activity per mg substance) of the AIIAs tested. Apparent K(i)-doses at 24 hours were within the dose range recommended for clinical use in patients with hypertension.

Adult↗