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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 19 recordsLinked to original sources
PubMed2007

Evaluation of a serological method for the detection of Taenia saginata cysticercosis using serum and meat juice samples.

Two peptides, HP6-2 and Ts45S-10, were used as antigens for the detection of antibodies against Taenia saginata cysticercosis in serum and meat juice samples using enzyme-linked immunosorbent assay (ELISA). Positive control samples were obtained from animals experimentally infected (serum) and from animals naturally infected (meat juice). The two peptides and a pooled preparation of both peptides were evaluated, and their cut-off points with both sample categories were calculated. ELISA results from these different peptides were compared. Sensitivity and specificity of HP6-2 using serum were calculated as being 100 and 98%, respectively, showing to be higher than the values for the other antigens used. The average optical density (OD) value for negative samples was 0.646, whereas it was 1.702 for the positive control samples. This peptide was used to examine serum samples from animals with cysts and random field serum samples. For meat juice samples the pooled peptides showed the highest sensitivity and specificity, as they were 100 and 95%, respectively. The average OD values for the negative and the positive reference meat juice samples were 0.379 and 1.291, respectively. The optimal dilution of the meat juice samples for the ELISA was very low, as it was 1:20 using the pooled peptides, compared with 1:800 serum dilution using HP6-2. To the authors' knowledge, this is the first report of a successful testing for T. saginata cysticercosis using meat juice.

Animals↗
PubMed2006

Effect of ethanol on cardiac single sodium channel gating.

Alcohol in modest and higher doses has the potential to induce cardiac arrhythmias. The most famous alcohol-related arrhythmia is the "holiday heart syndrome". Furthermore, there is a clear association between excessive alcohol consumption and the risk of sudden cardiac death. However, the acute effects of ethanol on arrhythmia induction are not well understood. The effect of ethanol on single cardiac sodium channels has not been studied yet. To elucidate the effect of ethanol on human cardiac sodium channels we performed a patch clamp study in HEK-293 cells overexpressing the human cardiac sodium channel. We used HEK-293 cells overexpressing the human cardiac sodium channel (Na(1.5)). Single channel gating was investigated by the cell-attached patch clamp technique. Sodium channel currents were elicited by depolarizing pulses from -120 to -20mV for a duration of 150ms. Single channel availability, open probability and peak average current were assessed baseline and after addition of ethanol in increasing concentrations (0.50 per thousand (10.9mM), 1.00 per thousand (21.7mM), 2.00 per thousand (43.5mM) and 4.00 per thousand (87.0mM)). We found a concentration-dependent reduction of open probability which was statistically significant at 2.00 per thousand ethanol (66.5+/-14% of control). At higher concentrations (4.00 per thousand) also availability decreased to 66.5+/-11.0% of control. This resulted in a significant decrease of peak average current at 2.00 per thousand and at 4.00 per thousand ethanol (61.8+/-7.4 and 53.0+/-8.2% of control). For the first time the present study demonstrates acute inhibitory effects of ethanol on single cardiac sodium channel gating and provides one potential mechanism for the well known clinical observation that ethanol triggers supraventricular and ventricular arrhythmias.

Cell Line↗
PubMed2006

30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial.

BACKGROUND: Carotid endarterectomy is effective in stroke prevention for patients with severe symptomatic carotid-artery stenosis, and carotid-artery stenting has been widely used as alternative treatment. Since equivalence or superiority has not been convincingly shown for either treatment, we aimed to compare the two. METHODS: 1200 patients with symptomatic carotid-artery stenosis were randomly assigned within 180 days of transient ischaemic attack or moderate stroke (modified Rankin scale score of < or =3) carotid-artery stenting (n=605) or carotid endarterectomy (n=595). The primary endpoint of this hospital-based study was ipsilateral ischaemic stroke or death from time of randomisation to 30 days after the procedure. The non-inferiority margin was defined as less than 2.5% on the basis of an expected event rate of 5%. Analyses were on an intention-to-treat basis. This trial is registered at Current Controlled Trials with the international standard randomised controlled trial number ISRCTN57874028. FINDINGS: 1183 patients were included in the analysis. The rate of death or ipsilateral ischaemic stroke from randomisation to 30 days after the procedure was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy (absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for non-inferiority is 0.09. INTERPRETATION: SPACE failed to prove non-inferiority of carotid-artery stenting compared with carotid endarterectomy for the periprocedural complication rate. The results of this trial do not justify the widespread use in the short-term of carotid-artery stenting for treatment of carotid-artery stenoses. Results at 6-24 months are awaited.

Aged↗
PubMed2006

PRIMA-1(MET) induces nucleolar accumulation of mutant p53 and PML nuclear body-associated proteins.

We have previously identified PRIMA-1, a low molecular weight compound that restores the transcriptional transactivation function to mutant p53 and induction of apoptosis. To explore the molecular mechanism for PRIMA-1-induced mutant p53-dependent apoptosis, we examined the intracellular distribution of mutant p53 upon treatment with PRIMA-1(MET) by immunofluorescence staining. We found that PRIMA-1(MET) induced nucleolar translocation of mutant p53 and the promyelocytic leukemia (PML) nuclear body-associated proteins PML, CBP and Hsp70. Levels of Hsp70 were significantly enhanced by PRIMA-1(MET) treatment. PRIMA-Dead, a compound structurally related to PRIMA-1 but unable to induce mutant p53-dependent apoptosis, failed to induce nucleolar translocation of mutant p53. Our results suggest that redistribution of mutant p53 to nucleoli plays a role in PRIMA-1-induced apoptosis.

Active Transport, Cell Nucleus↗
PubMed2006

A necrotic cell death model in a protist.

While necrotic cell death is attracting considerable interest, its molecular bases are still poorly understood. Investigations in simple biological models, taken for instance outside the animal kingdom, may benefit from less interference from other cell death mechanisms and from better experimental accessibility, while providing phylogenetic information. Can necrotic cell death occur outside the animal kingdom? In the protist Dictyostelium, developmental stimuli induced in an autophagy mutant a stereotyped sequence of events characteristic of necrotic cell death. This sequence included swift mitochondrial uncoupling with mitochondrial 2',7'-dichlorofluorescein diacetate fluorescence, ATP depletion and increased oxygen consumption. This was followed by perinuclear clustering of dilated mitochondria. Rapid plasma membrane rupture then occurred, which was evidenced by time-lapse videos and quantified by FACS. Of additional interest, developmental stimuli and classical mitochondrial uncouplers triggered a similar sequence of events, and exogenous glucose delayed plasma membrane rupture in a nonglycolytic manner. The occurrence of necrotic cell death in the protist Dictyostelium (1) provides a very favorable model for further study of this type of cell death, and (2) strongly suggests that the mechanism underlying necrotic cell death was present in an ancestor common to the Amoebozoa protists and to animals and has been conserved in evolution.

Animals↗
PubMed2006

Visual diagnosis of Taenia saginata cysticercosis during meat inspection: is it unequivocal?

A total of 267 cysts were collected from March to December 2004 from two main abattoirs in northern Germany. The cysts were classified by the usual organoleptic methods during meat inspection as Cysticercus bovis. The reported prevalence of cysticercosis in the abattoirs was 0.48 and 1.08%, respectively. The cysts were examined macroscopically for description of their morphology and constituents and classified as viable or degenerating (dead). The DNA was extracted from these cysts and subjected to polymerase chain reaction (PCR) for evaluation of the detection methods used and to make certain that the cysts did indeed belong to C. bovis, as indicated at the slaughterhouses. Two sets of primers were used with different sensitivity levels. The first, HDP1, was able to detect 200 fg of Taenia saginata DNA and 100 pg of C. bovis DNA. The other primer set, HDP2, was able to detect 1 pg of T. saginata DNA and 1 ng of C. bovis DNA. No more than 52.4% of the samples tested positive for C. bovis in the PCR using both primers, while 20% of the viable cysts and 49.2% of the degenerating cysts tested negative with both primers.

Abattoirs↗
PubMed2006

The RIONI study rationale and design: validation of the first stored electrograms transmitted via home monitoring in patients with implantable defibrillators.

Appropriate and inappropriate therapies of implantable cardioverter defibrillators (ICDs) have a major impact on morbidity and quality of life in ICD recipients. The recently introduced home monitoring of ICD devices is a promising new technique which remotely offers information about the status of the system. Stored intracardiac electrograms (IEGMs), which are essential for correct classification of appropriate and inappropriate ICD discharges, have until now not been available with ICD home monitoring on a day-by-day basis because of limitations of transferable data. We demonstrate the first compressed IEGMs daily transferable via home monitoring (IEGM-online). Validation of these electrograms will be performed in the Reliability of IEGM-Online Interpretation (RIONI) study. A total of 210 episodes of stored IEGMs will be collected by at least 12 European centres. The primary endpoint of this study is to investigate whether the IEGM-online based evaluation of the appropriateness of the ICDs therapeutic decision following episode detection is equivalent to the evaluation based on the complete ICD episode Holter extracted from the IEGM stored. The evaluation is independently done by an expert board of three experienced ICD investigators. The equivalence of the two methods is accepted if the evaluations yield a different conclusion for <10% of all evaluated IEGMs. The conclusion of the study is expected at the beginning of 2007. If RIONI successfully validates IEGMs transmitted via home monitoring, a strong basis for the use of this promising technique will be established.

Death, Sudden, Cardiac↗
PubMed2006

Cancer mortality in German carbon black workers 1976-98.

BACKGROUND: Few studies have investigated cancer risks in carbon black workers and the findings were inconclusive. METHODS: The current study explores the mortality of a cohort of 1535 male German blue-collar workers employed at a carbon black manufacturing plant for at least one year between 1960 and 1998. Vital status and causes of death were assessed for the period 1976-98. Occupational histories and information on smoking were abstracted from company records. Standardised mortality ratios (SMR) and Poisson regression models were calculated. RESULTS: The SMRs for all cause mortality (observed deaths (obs) 332, SMR 120, 95% CI 108 to 134), and mortality from lung cancer (obs 50, SMR 218, 95% CI 161 to 287) were increased using national rates as reference. Comparisons to regional rates from the federal state gave SMRs of 120 (95% CI 107 to 133) and 183 (95% CI 136 to 241), respectively. However, there was no apparent dose response relationship between lung cancer mortality and several indicators of occupational exposure, including years of employment and carbon black exposure. CONCLUSIONS: The mortality from lung cancer among German carbon black workers was increased. The high lung cancer SMR can not fully be explained by selection, smoking, or other occupational risk factors, but the results also provide little evidence for an effect of carbon black exposure.

Adult↗
PubMed2006

Efficacy of amphoteric surfactant- and peracetic acid-based disinfectants on spores of bacillus cereus in vitro and on food premises of the German armed forces.

In mass catering facilities of the German Armed Forces, foodborne outbreaks are commonly attributed to Bacillus cereus, and spores of this organism are regularly found on equipment surfaces. B. cereus is the causative agent of foodborne emetic or diarrheic disease. Hence, the use of sporicidal disinfectants may provide a starting point for successful risk mitigation of diseases associated with B. cereus. In this study, the amphoteric surfactant-based disinfectant (product A) that has been routinely used in catering facilities of the German Armed Forces and a peracetic acid-based disinfectant (product B) were compared for their efficacy against B. cereus spores in laboratory tests and under field conditions. In a carrier test for B. cereus spores, product A displayed no efficacy against spores of the test strain. In contrast, a substantial reduction in spore concentration (>5-log reduction) was achieved with product B. In a controlled trial conducted in seven Army catering facilities, the reduction in the number of B. cereus-positive samples was significantly greater (P < 0.001) for product B (from 28% initial contamination to 3% after application) than for product A (from 33 to 21%). Product B was estimated to be 6.25 times more efficacious than product A. Field trials confirmed the higher efficacy of the peracetic acid-based disinfectant to reduce B. cereus contamination on surfaces as found for the in vitro experiments. The tests used to assess the sporicidal effects of disinfectants were adequate under practice conditions and could be used for sporicidal testing of disinfectants for catering and food production establishments.

Bacillus cereus↗
PubMed2006

Organization of risk analysis in the EU and the new EU food regulation.

Given the scope and magnitude of the food supply in modern societies, there is no way to ensure that all foods are kept free from potential sources of contamination. Instead, food safety is enhanced by systematically concentrating upon minimizing opportunities for contamination at every point from food production and processing to distribution, preparation, and consumption. Although previous advances, such as pasteurization and refrigeration, and contemporary improvements in hazard analysis and control have significantly improved the safety of the food supply, foodborne disease remains a major cause of morbidity and mortality. Consequently, the food policy of the European Union and member states must reach the highest food safety standards in order to reduce the incidence of the illness produced by consumption of foods. To reach this goal, the new food regulation is in force since 2002 with the amendment through the hygiene package, which is in force since 2006. Risk Analysis forms the foundation on which food safety policy is based and an important part is aimed at microbiolgogical contamination. Additionally a European Food Safety Authority was established to carry out risk assessment and communication of food safety issues. At the same time, member states have created their own Food Safety Agencies working closely with the European Food Safety Authority. In this work, a description of the structure and work of the European Food Safety Authority and as an example the Spanish Food Safety Agency as well as key elements of the new regulation with special respect to the hygiene package is given.

Animals↗
PubMed2005

Expression of Ksp-cadherin during kidney development and in renal cell carcinoma.

Cadherins are a large family of cell-cell adhesion molecules acting in a homotypic, homophilic manner that play an important role in the maintenance of tissue integrity. In the human kidney, several members of the cadherin family (including E- and N-cadherin, cadherin-6, -8 and -11) are expressed in a controlled spatiotemporal pattern. Cadherin-16, also called kidney-specific (Ksp-) cadherin, is exclusively expressed in epithelial cells of the adult kidney. In renal cell carcinomas (RCCs), which are considered to originate from epithelial kidney tubular cells, a complex pattern of cadherin expression can be observed, but Ksp-cadherin expression has not been analysed so far. In the present study, we show that the expression of Ksp-cadherin is completely abrogated in RCCs. Whereas Ksp-cadherin can be detected at later stages of tubulogenesis during human renal development and in the distal tubules of adult kidneys, no expression was found by immunohistochemistry or Western blot analysis in RCC tumour tissues and several RCC cell lines. However, despite the lack of protein expression, mRNA synthesis of Ksp-cadherin could be detected by reverse transcriptase-polymerase chain reaction analysis in all RCC tissues and most of the RCC cell lines studied, although at a reduced level. The loss of Ksp-cadherin protein was only observed in the malignant part of the tumour kidneys, whereas in the normal part of the affected kidneys Ksp-cadherin expression was clearly detected. These results indicate a downregulation of Ksp-cadherin in RCC and suggest a role for this cell adhesion molecule in tumour suppression.

Blotting, Western↗
PubMed2005

[Cosmetic colorants. Toxicology and regulation].

Some recent publications raised concern over a possible link between hair dye use and the incidence of bladder tumours in a Californian population. The Scientific Committee for Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP) demanded the toxicological testing of all hair dyes used in Europe to exclude any risk. The EU commission initiated corresponding measures. Only safe hair dyes will be included on a positive list while all other hair dyes will be banned. The hair dye lawsone--the dyeing ingredient of henna--was evaluated by the SCCNFP as genotoxic but the BfR came to another conclusion. The regulation of both lawsone and henna remains an open question. Furthermore, some cosmetic colorants were critically discussed. The azo dyes CI 12150, CI 26100, CI 27290 and CI 20170 are allowed for use in cosmetics. On cleavage they form the carcinogenic aromatic amines o-anisidine, 4-aminoazobenzene and 2,4-xylidine, respectively. For three of these dyes the cleavage by human skin bacteria in vitro to the respective arylamine was shown experimentally. Further problems may arise from colorants used for tattoos and permanent makeup. These products up to now are not subject to legislation and there are no regulatory stipulations with respect to health safety and purity for colorants used for these purposes.

Carcinogenicity Tests↗
PubMed2005

Evolutionarily plastic regions at human 3p21.3 coincide with tumor breakpoints identified by the "elimination test".

We have previously found with the microcell hybrid-based "elimination test" that human chromosome 3 transferred into murine or human tumor cells regularly lost certain 3p regions during tumor growth in SCID mice. The most common eliminated region, CER1, is approximately 2.4 Mb at 3p21.3. CER1 breakpoints were clustered in approximately 200-kb regions at both telomeric and centromeric borders. We have also shown, earlier, that tumor-related deletions often coincide with human/mouse synteny breakpoints on 3p12-p22. Here we describe the results of a comparative genomic analysis on the CER1 region in Caenorhabditis elegans, Drosophila melanogaster, Fugu rubripes, Gallus gallus, Mus musculus, Rattus norvegicus, and Canis familiaris. First, four independent synteny breaks were found within the CER1 telomeric breakpoint cluster region, comparing human, dog, and chicken genomes, and two independent synteny breaks within the CER1 centromeric breakpoint cluster region, comparing human, mouse, and chicken genomes, suggesting a nonrandom involvement of tumor breakpoint regions in chromosome evolution. Second, both CER1 breakpoint cluster regions show recent tandem duplications (seven Zn finger protein family genes at the telomeric and eight chemokine receptor genes at the centromeric side). Finally, all genes from these regions underwent horizontal evolution in mammals, with formation of new genes and expansion of gene families, which were displayed in the human genome as tandem gene duplications and pseudogene insertions. In contrast the CER1 middle region contained evolutionarily well-conserved solitary genes and a minimal amount of retroposed genes. The coincidence of evolutionary plasticity with CER1 breakpoints may suggest that regional structural instability is expressed in both evolutionary and cancer-associated chromosome rearrangements.

Animals↗
PubMed2005

Shortening of the bovine tongue according to regulation (EC) 999/2001 is not complying with the current legal definition of specified risk material - a macroscopical and histological preliminary study.

The full elimination of all specified risk material (SRM) in food of animal origin is crucial for consumer protection and is of high priority in inner EU trade. Among other tissues, the tonsils of cattle are considered as SRM. The aim of this study was to evaluate whether the 'cut at the back of the tongue just before the tongue bones' required by EC regulation is sufficient to remove tonsils and lymphatic tissue completely. Eight skulls from cattle were collected for the simulation of a vertical cut according to the EC regulation and the detection of the target at the back of the tongue. Further, specimens of the lingual mucosa were cut out from two tongues and examined microscopically. The most caudal of these specimens was from the macroscopically visible part of the lingual tonsil. The most rostral specimen contained the most caudal Papilla vallata. Simulation of the obligatory ventro-dorsal cut yielded hits at varying locations on the dorsal surface of the tongue, sometimes including tissue of the lingual tonsil. Histological examination of the lingual mucosa gave clear evidence that lymphatic tissue resembling the tissue of a tonsil in terms of its histological organization and infiltration of the mucosal epithelium could even be found in areas with no macroscopically visible lingual tonsils.

Abattoirs↗
PubMed2005

Consumption, knowledge, and handling of raw meat: a representative cross-sectional survey in Germany, March 2001.

Outbreaks of gastroenteritis have been repeatedly associated with the consumption of raw meat and raw meat products. To assess the potential of this problem in Germany, frequency of consumption and knowledge about and handling of raw meat during food preparation in the German population was estimated. We conducted a population-based nationwide cross-sectional survey in private households in March 2001 by random telephone numbers. Consenting German-speaking persons were randomly chosen among household members for standardized interviews. Proportions were standardized by age, sex, and region (eastern and western Germany). A total of 510 people were interviewed (response 45.1%), including 62.3% women and 31.8% considered at high risk (children younger than 10 years old, elderly more than 65 years old, and chronically ill persons). The mean age was 45.7 years. Of those who ate raw ground meat at least once a week, 17.8% lived in eastern Germany and 5.1% in western Germany, (chi-square test, P < 0.001). Teewurst was eaten by 50.8% of all respondents and 53.8% of respondents in the high-risk group. That salami or Teewurst were raw meat products was known to 58.1 and 36.3% of the respondents, respectively. Respondents reported not washing their hands (46.6%) or cleaning their cutting boards with soap (48.1%) after preparing raw meat. A total of 10.3% of the respondents had diarrhea during the last 3 months. Although knowledge is poor, consumption of raw meat products is widespread in Germany, even among high-risk persons. More information is necessary on which products contain raw meat, the potential risk of diarrhea after raw meat products are consumed, and appropriate handling of raw meat products.

Adolescent↗
PubMed2004

Wild-type p53 activates SAP expression in lymphoid cells.

SAP is an adaptor molecule with one SH2 domain and it is expressed in activated T and NK cells, where it is required for the appropriate signaling from the SLAM family of surface receptors. Deleted or mutated SAP genes that encode functionally defective protein are associated with the X-linked lymphoproliferative disease (XLP). This primary immunodeficiency is characterized by extreme sensitivity to Epstein-Barr virus (EBV) infection, dysgammaglobulinemia and a high rate of lymphoma development. The vigorous T- and B-cell proliferation that follows EBV infection and the high incidence of lymphomas (30%) in XLP patients might reflect functional defects in cell cycle and/ or apoptosis control. Our experiments show that SAP is a target of p53. In Burkitt lymphoma (BL) lines transfected with a temperatur-sensitive (ts) p53, SAP mRNA and protein expression was dependent on wild-type (wt) p53. Activation of endogenous wt p53 in BLs and lymphoblastoid cell lines led to the induction of SAP and this was inhibited by the specific p53 inhibitor pifithrin-alpha. Cell lines that carried mutant p53 did not express SAP under similar conditions. Moreover, we have shown binding of wt p53 to the promoter region of SAP by ChIP assay. Our results suggest that SAP contributes to the execution of some p53 functions.

Base Sequence↗
PubMed2004

The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia.

In the past decades, a lot of effort has been put in identifying the role of matrix metalloproteinases (MMPs) in cancer. The main role of MMPs in angiogenesis, tumor growth and metastasis is degradation of extracellular matrix (ECM) and release and/or activation of growth factors through their degradative activity. The degradative activity finally results in cancer progression. MMP-inhibitors (MMPIs) have already been designed and tested, based on the degradative role of MMPs in cancer progression. First clinical trials with MMPIs have been performed with disappointing results, showing that in order to use MMP-inhibition the mechanisms underlying MMP-expression in cancer have to be further elucidated. This paper reviews the mechanisms of MMPs on molecular and cellular level and discusses the role for MMPs and MMP-inhibition in cancer with special focus on acute leukemia.

Acute Disease↗