Biomedical subjects

Klaus Guenther

Publications and source records attributed to Klaus Guenther.

11 recordsLinked to original sources

PubMed2006

Enantioselective separation and determination of single nonylphenol isomers.

It has recently become clear that an isomer specific view of technical 4-nonylphenol (NP) is absolutely necessary for the evaluation of the biological behavior of NP, raising additional questions concerning enantiomer specific effects. For the first time, in this study enantioselective HPLC was applied to enantiomeric separation of chiral NP isomers. A semipreparative separation of two NP isomers could be achieved. A GC-MS method has been developed for the simultaneous detection of three chiral NP isomers in water samples. Investigation of influent and effluent samples from a wastewater treatment plant in Germany indicated that enantioselective degradation could occur in the environment. In one examined influent, an enantiomer ratio of 1.7 for two different isomers was determined.

Chromatography, High Pressure Liquid↗

PubMed2005

Estrogen-active nonylphenols from an isomer-specific viewpoint: a systematic numbering system and future trends.

4-Nonylphenols (NPs) are very important environmentally relevant substances. They are persistent, toxic, endocrine-disrupting chemicals that are priority hazardous substances of the EU Water Framework Directive. NPs are degradation products of 4-nonylphenol ethoxylates (NPEs), a widely used group of nonionic surfactants. The technical synthesis of NP leads to a complex mixture of NPs consisting of isomeric compounds that have different branched nonyl side chains. It has recently become clear that an isomer-specific view is absolutely necessary when it comes to correctly evaluating the biological effects of NPs and their behavior in the environment, including degradation processes. To rationalize the identification of individual NP isomers in scientific studies, we have developed a numbering system for all possible NP isomers that follows the IUPAC rules of substituent characterization in alkylphenols. The 211 possible constitutional isomers of NP are numbered according to a hierarchical and logical system. In the future, multidimensional coupling systems--for example GCxGC-TOF-MS--will be needed to study these highly complex class of substances.

Chemistry, Organic↗

PubMed2005

Age and manifestation related symptoms in familial adenomatous polyposis.

BACKGROUND: To identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis. METHODS: We undertook a retrospective study of 143 FAP patients treated at the Department of Surgery, University of Erlangen between 1971 and 2000. We identified patterns of symptoms, endoscopic findings and extracolonic manifestations in three age groups. RESULTS: FAP was diagnosed clinically on the basis of symptoms in 84% (120/143) of these patients. Most presented with intestinal symptoms such as colonic bleeding (68%) and diarrhea (42%). All but one of the patients between 20 and 40 years old had rectal polyps (98.7%, 75/76), whereas in those over 40 years old the prevalence was 76% (35/46). Non-specific symptoms such as abdominal pain, fatigue and bloating were less frequent and were mainly reported by patients older than 40. CONCLUSION: The commonest presenting features of FAP are alteration of bowel habit and rectal bleeding, but both are found in many other conditions. Patients with these findings need immediate endoscopy to allow prompt diagnosis and prophylactic surgery.

Abdominal Pain↗

PubMed2005

A novel metabolic pathway for degradation of 4-nonylphenol environmental contaminants by Sphingomonas xenophaga Bayram: ipso-hydroxylation and intramolecular rearrangement.

Several nonylphenol isomers with alpha-quaternary carbon atoms serve as growth substrates for Sphingomonas xenophaga Bayram, whereas isomers containing hydrogen atoms at the alpha-carbon do not. Three metabolites of 4-(1-methyloctyl)-phenol were isolated in mg quantities from cultures of strain Bayram supplemented with the growth substrate isomer 4-(1-ethyl-1,4-dimethyl-pentyl)-phenol. They were unequivocally identified as 4-hydroxy-4-(1-methyl-octyl)-cyclohexa-2,5-dienone, 4-hydroxy-4-(1-methyl-octyl)-cyclohex-2-enone, and 2-(1-methyl-octyl)-benzene-1,4-diol by high pressure liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. Furthermore, two metabolites originating from 4-n-nonylphenol were identified as 4-hydroxy-4-nonyl-cyclohexa-2,5-dienone and 4-hydroxy-4-nonyl-cyclohex-2-enone by high pressure liquid chromatography-mass spectrometry. We conclude that nonylphenols were initially hydroxylated at the ipso-position forming 4-alkyl-4-hydroxy-cyclohexa-2,5-dienones. Dienones originating from growth substrate nonylphenol isomers underwent a rearrangement that involved a 1,2-C,O shift of the alkyl moiety as a cation to the oxygen atom of the geminal hydroxy group yielding 4-alkoxyphenols, from which the alkyl moieties can be easily detached as alcohols by known mechanisms. Dienones originating from nongrowth substrates did not undergo such a rearrangement because the missing alkyl substituents at the alpha-carbon atom prevented stabilization of the putative alpha-carbocation. Instead they accumulated and subsequently underwent side reactions, such as 1,2-C,C shifts and dihydrogenations. The ipso-hydroxylation and the proposed 1,2-C,O shift constitute key steps in a novel pathway that enables bacteria to detach alpha-branched alkyl moieties of alkylphenols for utilization of the aromatic part as a carbon and energy source.

Carbon Isotopes↗

PubMed2005

A prospective two-center study comparing wireless capsule endoscopy with intraoperative enteroscopy in patients with obscure GI bleeding.

BACKGROUND: Capsule endoscopy enables noninvasive diagnostic examination of the entire small intestine. However, sensitivity and specificity of capsule endoscopy have not been adequately defined. We, therefore, compared capsule endoscopy by using intraoperative enteroscopy as a criterion standard in patients with obscure GI bleeding. METHODS: Forty-seven consecutive patients with obscure GI bleeding (11 with ongoing overt bleeding, 24 with previous overt bleeding, and 12 with obscure-occult bleeding) from two German gastroenterologic centers were included. All patients who had a prior nondiagnostic evaluation, including upper endoscopy, colonoscopy with a retrograde examination of the distal ileum, and push enteroscopy, underwent capsule endoscopy followed by intraoperative enteroscopy. RESULTS: Capsule endoscopy identified lesions in 100% of the patients with ongoing overt bleeding, 67% of the patients with previous overt bleeding, and 67% of the patients with obscure-occult bleeding. Angiectasias were the most common source of bleeding (n = 22). Capsule endoscopy showed the source of bleeding in 74.4% of all patients. The method was more effective in patients with ongoing bleeding. Compared with intraoperative enteroscopy sensitivity, specificity, and positive and negative predictive values of capsule endoscopy were 95%, 75%, 95%, and 86%, respectively. CONCLUSIONS: Capsule endoscopy has high sensitivity and specificity to detect a bleeding source in patients with obscure GI bleeding. Thus, wireless capsule endoscopy can be recommended as part of the routine work-up in patients with obscure GI bleeding.

Adolescent↗

PubMed2005

Differential degradation of nonylphenol isomers by Sphingomonas xenophaga Bayram.

Sphingomonas xenophaga Bayram, isolated from the activated sludge of a municipal wastewater treatment plant, was able to utilize 4-(1-ethyl-1,4-dimethylpentyl)phenol, one of the main isomers of technical nonylphenol mixtures, as a sole carbon and energy source. The isolate degraded 1 mg of 4-(1-ethyl-1,4-dimethylpentyl)phenol/ml in minimal medium within 1 week. Growth experiments with five nonylphenol isomers showed that the three isomers with quaternary benzylic carbon atoms [(1,1,2,4-tetramethylpentyl)phenol, 4-(1-ethyl-1,4-dimethylpentyl)phenol, and 4-(1,1-dimethylheptyl)phenol] served as growth substrates, whereas the isomers containing one or two hydrogen atoms in the benzylic position [4-(1-methyloctyl)phenol and 4-n-nonylphenol] did not. However, when the isomers were incubated as a mixture, all were degraded to a certain degree. Differential degradation was clearly evident, as isomers with more highly branched alkyl side chains were degraded much faster than the others. Furthermore, the C9 alcohols 2,3,5-trimethylhexan-2-ol, 3,6-dimethylheptan-3-ol, and 2-methyloctan-2-ol, derived from the three nonylphenol isomers with quaternary benzylic carbon atoms, were detected in the culture fluid by gas chromatography-mass spectrometry, but no analogous metabolites could be found originating from 4-(1-methyloctyl)phenol and 4-n-nonylphenol. We propose that 4-(1-methyloctyl)phenol and 4-n-nonylphenol were cometabolically transformed in the growth experiments with the mixture but that, unlike the other isomers, they did not participate in the reactions leading to the detachment of the alkyl moiety. This hypothesis was corroborated by the observed accumulation in the culture fluid of an as yet unidentified metabolite derived from 4-(1-methyloctyl)phenol.

Alcohols↗

PubMed2004

Common denominator genes that distinguish colorectal carcinoma from normal mucosa.

PURPOSE: Microarray technology has been used by a growing number of investigators and several studies have been published that list hundreds of genes differentially expressed by colorectal carcinoma (CRC) and normal mucosa (MC). On the basis of our own and other investigators' microarray data, our goal was to identify a common denominator gene cluster distinguishing CRC from MC. METHODS: Thirty GeneChips (HG-U133A, Affymetrix) were hybridized, 20 with RNA of CRC stages I-IV (UICC) and 10 with MC. Expression signals showing at least a 4-fold difference between CRC and MC (p<0.01) were identified as differentially expressed. In addition, in our integrative data analysis approach only those genes whose expression was altered simultaneously in at least 2 of 5 recently published studies were subjected to an unsupervised hierarchical cluster analysis. RESULTS: We detected 168 up- and 283 down-regulated genes in CRC relative to MC. Twenty-three genes were filtered from the five articles reviewed. An unsupervised hierarchical cluster analysis of these 23 genes confirmed the high specificity of these genes to differentiate between CRC and MC in our microarray data. CONCLUSIONS: Colorectal cancer and mucosa could be clearly separated by 23 genes selected for being differentially expressed more than once in a recent literature review. These genes represent a common denominator gene cluster that can be used to distinguish colorectal MC from CRC.

Carcinoma↗

PubMed2004

Contribution to the structural elucidation of 10 isomers of technical p-nonylphenol.

Gas chromatography-mass spectrometry (GC-MS) with a 100 m capillary column at different oven temperatures is employed to separate isothermally p-nonylphenol into 21 isomers. Analysis of the resulting mass spectra of these isomers indicates that they could be classified into six groups with respect to different configurations of the alpha- and beta-C-atoms on the alkyl chains. Based on these basic structures nonylphenol isomers are synthesized and also characterized by GC-MS. The obtained data elucidate the complete structures of 10 nonylphenol isomers of the technical mixture. The most important features of the mass spectra and the 1H and 13C nuclear magnetic resonance (NMR) spectra of these isomers are presented.

Environmental Pollutants↗

PubMed2004

Tissue preparation for gene expression profiling of colorectal carcinoma: three alternatives to laser microdissection with preamplification.

Colorectal-carcinoma specimens are heterogeneous and include areas of nonmalignant mucosal and connective tissue. For those study designs in which laser microdissection and RNA preamplification are impracticable, the optimal yield of genuine cancer RNA is a key factor in gene-expression analysis. In this study we compared alternative methods of tissue purification. Three contiguous 0.5-cm(3) samples taken from an advanced primary adenocarcinoma of the sigmoid colon were processed immediately after surgery with the use of the following methods: (1) cryotomy after manual dissection (CMD), (2) microscopically assisted manual dissection (MAMD), and (3) tumor-cell isolation with the use of Ber-EP4 antibodies and Dynabeads (Dynal Biotech GmbH, Hamburg, Germany; technique abbreviated as DB). We generated gene-expression profiles with the use of GeneChip technology (Affymetrix, Santa Clara, Calif) and recorded preparation times, costs, and RNA quantity and quality. CMD took 60 minutes, MAMD 180 minutes, and DB 90 minutes to isolate 22, 8, and 23 microg of RNA, respectively. Expenses for materials amounted to 41, 23, and 91 US dollars for CMD, MAMD, and DB, respectively. The 3'/5' ratio, as determined with the GeneChips, for GAPDH/beta-actin was 1.01:1.03 for CMD, 1.13:1.28 for MAMD, 1.43:1.68 for DB, K-ras, APC, smad 2, transforming growth factor-beta, and p53 were marked as present in all cases, with the exception of APC, which was graded as marginal on DB. The correlation values of gene-expression profiles were 91% (CMD/DB), 93% (CMD/MAMD), and 97% (DB/MAMD). All 3 methods provided enough RNA, of sufficient quality, for gene-expression microarray analysis in colorectal carcinoma. Cross-methodologic analyses of array data should not be performed uncritically.

Adenocarcinoma↗

PubMed2003

Endoscopic light-induced autofluorescence spectroscopy for the diagnosis of colorectal cancer and adenoma.

To evaluate the new, bio-optical method of light-induced autofluorescence spectroscopy for the endoscopic in-vivo diagnosis of (pre)-cancerous lesions of the colorectum, 311 endogenous fluorescence spectra were obtained from normal, adenomatous and cancerous colorectal tissue in 11 patients with cancer, six patients with familial adenomatous polyposis, and six patients with multiple adenomatous polyps. A light source delivered either white or violet-blue light for excitation of tissue autofluorescence via a flexible endoscope. Endogenous fluorescence spectra emitted by the tissue were picked up with a fiberoptic probe and analysed with a spectrograph. Biopsies were taken for definitive classification of the spectra. Rectal cancer (n=11) as well as adenomas with severe dysplasia (n=19) showed specific differences between the emitted fluorescence spectra as compared with normal mucosa and hyperplastic polyps. Having applied a mathematical algorithm to the spectra, a sensitivity of 96% and a specificity of 93% were obtained for the diagnosis of rectal cancer. The equivalent values for the diagnosis of dysplastic ademomas were 98 and 89%, respectively. Light-induced autofluorescence spectroscopy is a new and promising bio-optical procedure for the endoscopic in-vivo diagnosis of colorectal cancer and dysplasia.

Adenoma↗

PubMed2002

Endocrine disrupting nonylphenols are ubiquitous in food.

4-Nonylphenols (NPs) are common products of biodegradation of a widely used group of nonionic surfactants, the nonylphenol ethoxylates (NPEs). These compounds are known to be persistent, toxic, and estrogen active. There is a worldwide scientific and public discussion on the potential consequences of human long term dietary exposure to such endocrine disrupters. Despite numerous determinations of NPs in environmental samples no systematical reports exist relating to concentrations of NPs in food. We analyzed NPs in 60 different foodstuff commercially available in Germany. The results indicate that NPs are ubiquitous in food. The concentrations of NPs on a fresh weight basis varied between 0.1 and 19.4 microg/kg regardless of the fat content of the foodstuff. Based on data on German food consumption rates and these first analyses of NPs in food, the daily intake for an adult was calculated to be 7.5 microg/day NPs. For infants exclusively fed with breast milk or infant formulas daily intakes of 0.2 microg/day and 1.4 microg/day NPs, respectively, can be estimated.

Adolescent↗