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Biomedical subjects

M Exner

Publications and source records attributed to M Exner.

At least 55 records · Page 3Linked to original sources

Disinfectant activity against different morphological forms of Helicobacter pylori: first results.

The pathogenic bacterium Helicobacter pylori, which has infected more than one-half of the world's human population, exists in two morphological forms; the viable helical form and the disputed viable-but-not-culturable coccoid form. Infection by the helical form proceeds through the oral-oral route, while that by the coccoid form, if possible at all, is by the faecal-oral and/or the oral-oral route. The present pilot study addresses the question of disinfectant efficacy against both forms of the bacterium.

Chemistry, Pharmaceutical↗

Targeting the dust.

Explore the source record for details and available documents.

Blood Cell Count↗

Homozygosity for the C-->T polymorphism at nucleotide 46 in the 5' untranslated region of the factor XII gene protects from development of acute coronary syndrome.

Recently, a C-->T polymorphism at nucleotide 46 in the 5'-untranslated region of the factor XII (FXII) gene was shown to be associated with lower levels of FXII. To study the impact of this polymorphism on the development of an acute coronary syndrome (ACS), we compared 303 patients with ACS and 227 patients with stable coronary artery disease (CAD). In the latter group, 54.2% of individuals carried wild-type FXII:46C, 37.9% were heterozygous FXII:C46T and 7.9% were homozygous for FXII:46T. In contrast, in the ACS group (n = 303), 54.1% were wild-type FXII:46C, 42.6% were heterozygous FXII:C46T and only 3.3% carried the homozygous FXII:46T genotype. The 2.5-fold lower prevalence of the FXII:46T genotype in patients with ACS could indicate a protective effect on the development of ACS (odds ratio = 0.4, 95% CI 0.1-0.9) in patients with pre-existing CAD.

5' Untranslated Regions↗

Hygiene and health - the need for a holistic approach.

The holistic principles of hygiene and public health have contributed substantially to an increase in life expectancy by more than 30 years and in life quality since the beginning of the 20th century. Frank, Pettenkofer, Nightingale, Pasteur, Lister, and Koch have been pioneering protagonists of the holistic approach to hygiene and public health. Socioeconomic development and related factors such as nutrition status and food hygiene, housing conditions, water supply and sewage systems, and education (including motivation for personal hygiene) have obviously been of more importance for life expectancy and life quality than progress in curative medicine, such as availability of microbial diagnosis, vaccination, and antibiotics. Today, new risk factors for infectious diseases arise, even in developed countries. These risk factors arise from emerging pathogens, antibiotic-resistant microorganisms, changing demographic patterns, an increasing amount of ambulatory and home care, socioeconomic and environmental changes, technical environments, worldwide distribution of food, and changing human behavior with a decreased awareness of microbial threats. These new challenges worldwide make a renewal of the holistic approach of hygiene and public health both urgent and necessary. On the basis of historic experience, policies that focus on surveillance and control, diagnosis, and therapy only can be assumed to be both insufficient and inefficient in controlling the new challenges in infectious diseases. Experiences in Germany with a holistic hospital hygiene strategy since 1976 provide encouragement for the promotion of holistic health concepts. Risk assessment, risk management, and risk communication are basic steps of a modern holistic strategy. Hygiene has the potential to act as a moderator of diverging positions of different disciplines within this renewed approach.

Communicable Disease Control↗

Reverse transcriptase template switching during reverse transcriptase-polymerase chain reaction: artificial generation of deletions in ribonucleotide reductase mRNA.

Using reverse transcriptase-polymerase chain reaction (RT-PCR), we have recently described a bona fide deletion within the coding sequence of the large subunit of ribonucleotide reductase (R1) mRNA in colon cancer. Consecutive studies have raised questions about the nature of this phenomenon, because the corresponding genomic alteration at the DNA level or an aberrant protein could not be detected. Thus we considered an in vitro artifact during RT-PCR as a possible explanation for this observation. In contrast to reverse transcriptase, Taq DNA polymerase or C. therm DNA polymerase did not generate the aberrant product, suggesting the demand for the template switching activity intrinsic to retroviral reverse transcriptases. In fact, virtually the same deletion was observed in RT-PCR experiments when in vitro transcribed R1 mRNA was used. Considering structural prerequisites for template switching within R1 mRNA, we show that two direct repeats adjacent to a strong stem-loop secondary structure flank the deleted region of 1851 base pairs. Because several mRNAs encoding proteins of clinical and diagnostic importance fulfill these criteria, template switching enhances the potential risk of observing artifacts when interpreting results from RT-PCR studies. As shown in the present example, this may involve the artificial generation and the misinterpretation of PCR fragments amplified from targets relevant to tumor biology or cancer pharmacology. As a possible solution, one-step PCR with C. therm polymerase should be considered. This polymerase eliminates the artificial generation of aberrant mRNA signals observed during cDNA synthesis.

Adenocarcinoma↗

GIS-based analysis of drinking-water supply structures: a module for microbial risk assessment.

Water-related infections constitute an important health impact world-wide. A set of tools serving for Microbial Risk Assessment (MRA) of waterborne diseases should comprise the entire drinking-water management system and take into account the Hazard Analysis and Critical Control Point (HACCP) concept which provides specific Critical Control Points (CCPs) reflecting each step of drinking-water provision. A Geographical Information System (GIS) study concerning water-supply structure (WSS) was conducted in the Rhein-Berg District (North Rhine-Westphalia, Germany). As a result, suitability of the existing water databases HYGRIS (hydrological basis geo-information system) and TEIS (drinking-water recording and information system) for the development of a WSS-GIS module could be demonstrated. Spatial patterns within the integrated raw and drinking-water data can easily be uncovered by GIS-specific options. The application of WSS-GIS allows a rapid visualization and analysis of drinking-water supply structure and offers huge advantages concerning microbial monitoring of raw and drinking water as well as recognition and investigation of incidents and outbreaks. Increasing requests regarding health protection and health reporting, demands for a better outbreak management and water-related health impacts of global climate change are major challenges of future water management to be tackled with methods including spatial analysis. GIS is assumed to be a very useful tool to meet these requirements.

Environmental Monitoring↗

A geographical information system (GIS) as a tool for microbial risk assessment in catchment areas of drinking water reservoirs.

The main tributaries of three drinking water reservoirs of Northrhine-Westfalia (Germany) were monitored within a 14-month period mainly for bacterial and parasitic contamination. In this context a detailed geo-ecological characterisation within the differing catchment areas was carried out to reveal a reliable informational basis for tracing back the origin of microbial loads present in the watercourses. To realise a microbial risk assessing geo-ecological information system (MRA-GIS), a Geographical Information System (GIS) has been implemented for the study areas. The results of the microbiological investigations of the watercourses showed an input of pathogens into all three of the tributaries. It could be demonstrated that the use of MRA-GIS database and some GIS-techniques substantially support the spatial analysis of the microbial contamination patterns. From the hygienic point of view, it is of the utmost importance to protect catchment areas of surface water reservoirs from microbial contamination stemming from human activities and animal sources. This constitutes essential part of the multi-barrier concept which stresses the importance of reducing diffuse and point pollution in catchment areas of water resources intended for human consumption. MRA-GIS proves to be helpful to manage multi-barrier water protection in catchment areas and ideally assists the application of the HACCP concept on drinking water production.

Environmental Monitoring↗

Genistein prevents the glucose autoxidation mediated atherogenic modification of low density lipoprotein.

Hyperglycemia has been assumed to be responsible for oxidative stress in diabetes. In this respect, glucose autoxidation and advanced glycation end products (AGE) may play a causal role in the etiology of diabetic complications as e.g. atherosclerosis. There is now growing evidence that the oxidative modification of LDL plays a potential role in atherogenesis. Glucose derived oxidants have been shown to peroxidise LDL. In the present study, genistein, a compound derived from soy with a flavonoid chemical structure (4', 5, 7-trihydroxyisoflavone) has been evaluated for its ability to act as an antioxidant against the atherogenic modification of LDL by glucose autoxidation radical products. Daidzein, (4',7-dihydroxyisoflavone) an other phytoestrogen of soy, was tested in parallel. Genistein--in contrast to daidzein--effectively prevented the glucose mediated LDL oxidation as measured by thiobarbituric acid-reactive substance formation (TBARS), alteration in electrophoretic mobility, lipid hydroperoxides and fluorescence quenching of tryptophan residues of the lipoprotein. In addition the potential of glucose-oxidized LDL to increase tissue factor (TF) synthesis human endothelial cells (HUVEC) was completely inhibited when genistein was present during LDL oxidative modification by glucose. Both phytoestrogens did not influence the nonenzymatic protein glycation reaction as measured by the in vitro formation of glycated LDL. As the protective effect of genistein on LDL atherogenic modification was found at glucose/genistein molar ratios which may occur in vivo, our findings support the suggested beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.

Cells, Cultured↗

Endothelial C4d deposition is associated with inferior kidney allograft outcome independently of cellular rejection.

BACKGROUND: Capillary deposition of complement split product C4d has been suggested to be a valuable marker for humoral rejection. In this retrospective study we evaluated the clinical impact of C4d deposition in renal allografts with special emphasis on associations between C4d staining patterns and histological features of acute rejection. METHODS: One hundred and two allograft biopsies obtained from 61 kidney transplants (1-532 days after transplantation; median 14 days) were examined by immunohistochemistry on routine paraffin sections using a novel anti-C4d polyclonal antibody (C4dpAb). RESULTS: Fourty-two of 102 biopsies showed endothelial C4d deposits in peritubular capillaries (PTC). Histopathological analysis revealed a significantly lower frequency of positive C4d staining in biopsies with rather than in those without acute cellular rejection defined by the Banff grading schema (P<0.01). For clinical evaluation, patients were classified according to C4d staining in allografts (C4d(PTC) positive in at least one biopsy, n=31 vs C4d(PTC) negative in all biopsies, n=30). C4d(PTC) positive patients had significantly higher serum creatinine levels than C4d negative patients. Even in the absence of morphological evidence for rejection, differences in serum creatinine levels between C4d(PTC) positive and negative recipients were significant (6 months: 2.01+/-0.75 vs 1.41+/-0.27 mg/dl; 12 months: 1.95+/-0.60 vs 1.36+/- 0.34 mg/dl; 18 months: 1.98+/-0.50 vs 1.47+/-0.31 mg/dl; P<0.05). All patients with rejection resistant to conventional therapy (n=4) were in the C4d(PTC) positive subgroup. All recipients with panel reactive antibodies (PRA) >50% (n=8) were C4d(PTC) positive. CONCLUSIONS: Our data indicate that endothelial C4d deposition is associated with inferior graft outcome. We provide evidence that this immunohistochemical finding and its clinical impact are not associated with morphological signs of cellular rejection.

Biopsy↗

Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with restenosis after percutaneous transluminal angioplasty.

PURPOSE: To determine if an association exists between postdilation restenosis and heme oxygenase-1 (HO-1), which is induced by balloon injury and inhibits neointimal formation through the action of endogenous carbon monoxide. A dinucleotide repeat in the promoter region of the HO-1 gene shows a length polymorphism that modulates the level of gene transcription. METHODS: This cohort study included 96 consecutive patients (64 men; median age 69 years, interquartile range 60-75) who underwent successful balloon dilation in the femoropopliteal segment. Six-month patency was evaluated using oscillography, ankle-brachial index, and duplex sonography. The association of patency and the length of (GT) repeats in the HO-1 gene promoter was assessed in univariate and multivariate analyses. RESULTS: Restenosis was found in 23 (24%) patients within the first 6 months. Patients with short (<25 GT) dinucleotide repeats in the HO-1 gene promoter on either allele had restenosis significantly less often than patients with longer (> or = 25 GT) dinucleotide repeats (p = 0.01). Multivariate analysis revealed a significantly reduced risk for restenosis in these patients compared to patients without the short allele (odds ratio 0.2, 95% Cl 0.06 to 0.70, p = 0.007). CONCLUSIONS: Genetic risk factors for restenosis after percutaneous transluminal angioplasty have not been investigated. In this patient population, short repeat alleles of the heme oxygenase-1 gene promoter polymorphism were associated with reduced postdilation restenosis at 6 months. Upregulation of HO-1 may be an important protective factor after balloon angioplasty by inhibition of vascular smooth muscle cell proliferation.

Aged↗

Restenosis after percutaneous transluminal angioplasty in the femoropopliteal segment: the role of inflammation.

PURPOSE: To determine the value of baseline C-reactive protein (CPR), fibrinogen, and white blood cell (WBC) counts in predicting 1-year patency after percutaneous transluminal angioplasty (PTA) in the femoropopliteal segment. METHODS: In a retrospective cohort study, 168 consecutive patients (103 men; median age 70 years, interquartile range 61-77) who underwent successful PTA of the femoral and/or popliteal arteries were analyzed. Twelve-month patency was evaluated using oscillography, ankle brachial index, duplex sonography, and angiography. The predictive value of inflammatory markers was assessed in a multivariate model controlling for cardiovascular risk factors, technical success, and hemodynamic factors. RESULTS: Transient WBC elevation was found 6 hours after PTA, but this returned to baseline after 24 hours. Fibrinogen was elevated at 24 hours. Duplex scanning disclosed restenosis in 66 (39%) patients within the first 12 months after PTA. Only residual postdilation stenosis (> or = 30%) in the target segment (odds ratio 3.6, p=0.001) and baseline CRP levels (odds ratio 4.2, p=0.02) were independent predictors of outcome; neither WBC counts nor fibrinogen levels at any time point was associated with restenosis. CONCLUSIONS: Primary technical success and postinterventional hemodynamic flow at the dilated segment seem to be more important for intermediate-term patency than atherogenic risk factors. The predictive value of preprocedural serum CRP levels on restenosis should be further investigated.

Aged↗

Successful vaccination for Lyme disease: a novel mechanism?

Borrelia burgdorferi sensu lato is the aetiologic agent of Lyme disease, which is a multi-system disorder resulting from the transmission of organisms from an infected tick. According to the US Centers for Disease Control, the incidence of Lyme disease in the US has increased 25-fold since national surveillance began and the geographical spread of Lyme disease causing spirochetes would indicate that the annual number of cases will continue to rise. Humoral immunity has been shown to play a role in protection and this has spurred efforts towards developing a Lyme disease vaccine. A number of protective immunogens have been characterised to date, but due to the heterogeneity of Lyme disease Borreliae, no single molecule has proven to be completely effective as a vaccinogen. This review will describe the immunogens that have been used to protect against B. burgdorferi infection, with a focus on the inherent challenges involved with providing successful immunity to B. burgdorferi. In addition, the promising aspects and the limitations of each protective immunogen will be discussed.

Animals↗

Effect of intradermal tumor necrosis factor-alpha-induced inflammation on coagulation factors in dermal vessel endothelium. An in vivo study of human skin biopsies.

Inflammatory mediators were shown to exert procoagulant effects on cultured human endothelial cells (EC). In the present study the effect of intradermal application of tumor necrosis factor-alpha (TNF-alpha) on the expression of factors involved in regulation of coagulation at the EC surface, i.e. tissue factor (TF), thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) was studied in humans in vivo. The endothelial expression of these factors was evaluated immunohistochemically in biopsies taken after intradermal application of 5000 U TNF-alpha in 8 healthy volunteers. After 6 and 22 h biopsies were taken from the injection sites. At TNF-alpha injected sites typical inflammatory changes. e.g. EC upregulation of adhesion molecules and accumulation of leukocytes were detected. In parallel we could document EC expression of TF, downregulation of TM and depletion of tissue factor pathway inhibitor (TFPI) in inflamed areas. Early depletion of endothelial IkappaB alpha at the site of inflammation after application of TNF-alpha points to an activation of the NF-kappaB pathway. Our data suggest that, as shown in in vitro experiments, TNF-alpha activates the NF-kappaB pathway and induces specific procoagulant changes of EC due to expression of TF, down-regulation of TM and depletion of TFPI in vivo in humans. This procoagulant shift in the haemostatic balance on the cell surface, caused by TNF-alpha-induced inflammation, is likely to contribute to thrombosis associated with tissue inflammation in humans.

Adolescent↗