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K Günther

Publications and source records attributed to K Günther.

At least 55 records · Page 3Linked to original sources
PubMed1998

Rapid RT-PCR-based protein truncation test in the screening for 5' located mutations of the APC gene.

Although in vitro protein synthesis is a rapid method to screen for translational stops in the adenomatous polyposis coli (APC) gene, truncating mutations at the 5' most end are at risk of being overseen due to their small size. The authors describe a reverse transcriptase-polymerase chain reaction (RT-PCR)-based protein truncation test specifically designed for detecting truncated polypeptide chains of less than 10 kDa. Using this detection system, three novel germline mutations in familial adenomatous polyposis (FAP) patients were identified, i.e. a Gly101 Ter non-sense mutation in exon 3, an exon 4 splice acceptor mutation and a 555delC deletion in exon 5. Morever, a patient manifesting congenital hypertrophy of the retinal pigmented epithelium (CHPRE) was detected with an Arg232Ter mutation in exon 6. This is, to the authors' knowledge, the fourth exception to the rule that FAP patients manifesting CHRPE harbour genetic alternations downstream from APC exon 9. Hence, an alternative hotspot for non-sense mutations associated with CHRPE appears to encompass the codons 215, 216 and 232. Patients reported in this study, exhibited relatively mild clinical symptoms with respect to the age of onset of malignancy (> 50 years of age) and the number of polyps (70-100 adenomas). However, manifestation of severe duodenal adenomatosis was independent of the attenuated colorectal FAP phenotype.

Adenomatous Polyposis Coli Protein↗
PubMed1998

Predictive value of nuclear beta-catenin expression for the occurrence of distant metastases in rectal cancer.

PURPOSE: Adenomatous polyposis coli protein, glycogen synthetase kinase-3-beta, T cell transcription factor/lymphoid enhancer-binding factor, and beta-catenin modulate cell differentiation and proliferation via the expression of effector genes. It has recently been postulated that beta-catenin is a potent oncogene of sporadic colorectal carcinogenesis and a prognostic tumor marker. Our aim was to investigate whether the nuclear overexpression of beta-catenin, possibly caused by mutations in exon 3 of beta-catenin (CTNNB1), is correlated with distant metastatic spread or disease-free survival in rectal carcinoma. METHODS: Immunohistochemical analysis was performed with an anti-beta-catenin-monoclonal antibody on paraffin sections of two groups of patients (n = 2 x 77) with rectal carcinoma curatively treated by surgery alone. The patients selected were all free of local disease, to exclude surgical influence. Patient groups were matched for age, gender, International Union Against Cancer stage, and year of operation (1982 to 1991) and differed only in subsequent metachronous distant metastatic spread. Follow-up was prospective (median, 9.6 years). Three staining patterns were defined: membranous (normal), diffuse cytoplasmic (pathologic), and intense nuclear staining (pathologic). When intense nuclear staining was defined, the specimen was microdissected. Then, DNA was isolated, polymerase chain reaction-amplified, and sequenced to detect mutations in exon 3. RESULTS: Nuclear overexpression of beta-catenin correlated neither with distant metastatic spread (chi-squared, 0.37; P = 0.79) nor with disease-free survival (log-rank with trend, P = 0.62). No mutations were found in the area of the serine/threonine-kinase glycogen synthetase kinase-3-beta-phosphorylation site in exon 3 (CTNNB1) of beta-catenin. CONCLUSION: Although beta-catenin seems to play an important role in early colorectal carcinogenesis, its value as a prognostic marker is questionable. It must be assumed that metastatic ability is determined by other factors than the disturbance of the beta-catenin T cell transcription factor/lymphoid enhancer-binding factor cascade and that other mechanisms might cause the observed nuclear translocation of beta-catenin.

Adenocarcinoma↗
PubMed1998

[Post-traumatic arteriovenous fistula between splenic artery and vein as a rare cause of acute myocardial ischemia].

Arteriovenous fistulas of the portal system are rare. Congenital fistulas have to be differentiated from acquired fistulas; the latter are of posttraumatic or iatrogenic origin. The case presented demonstrates a history of diffuse abdominal pain and the first description of myocardial ischemia caused by a posttraumatic splenic arterioportal fistula. After diagnostic and therapeutic difficulties, the definitive treatment consisted in resection of the fistula system including the pancreatic tail.

Adult↗
PubMed1998

Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front.

Sixty to eighty percent of all colorectal cancers are characterized by mutations in the APC tumor suppressor gene. Recently, it was shown that these mutations lead to a nuclear overexpression of beta-Catenin by disruption of the wingless/WNT signal pathway. Since nuclear beta-Catenin functions as a transcriptional activator of hitherto unknown tumor genes, this form of beta-Catenin is now considered a major oncoprotein in colorectal cancer. Using immunohistochemistry, we investigated the distribution of overexpressed beta-Catenin within individual colorectal carcinomas. In the majority of the tumors, we found no homogeneous staining, but a strong nuclear expression of beta-Catenin predominantly localized at the invasion front with strongest nuclear staining of isolated, scattered tumor cells. In contrast, cells in the tumor center often showed no nuclear staining, but retained a membranous expression of beta-Catenin, comparable to normal colon epithelium. It is, therefore, likely that in addition to the overexpression of beta-Catenin caused by defects in the APC locus, regulatory events in the tumor itself lead to a different distribution of this oncoprotein. Possibly, surrounding tissue at the invasion front can give signals to the tumor cells, leading to a nuclear translocation of beta-Catenin, where it may play a direct role in tumor invasion processes.

Cell Nucleus↗
PubMed1998

["Benign metastasizing leiomyoma"? A case report without evidence for unbalanced cytogenetic aberrations].

There are rare cases of histologically benign appearing uterine leiomyomas with subsequent development of multifocal extrauterine smooth muscle tumors, most often located in the lung. It remains unclear whether this evolves from a morphological innocent appearing low grade sarcoma or from proliferation of multifocal but autochtonous cellular foci. Frequently, and in part recurrent karyotypic abnormalities were described for leiomyomas and leiomyosarcomas. Thus, we looked for imbalanced genetic aberrations in a case of a "benign metastasizing leiomyoma" by means of comparative genomic hybridisation (CGH). A 46-year-old female developed multiple bilateral lung nodules 4 years after hysterectomy. Fine needle biopsy of one nodule and subsequent resection of three lung nodules were performed. These and the hysterectomy specimen were investigated by histology, immunohistochemistry and CGH. Revision of the hysterectomy specimen revealed multiple leiomyomas without any evidence for malignancy. Lung nodules were composed of benign appearing smooth muscle cells with epithelial lined cleft-like spaces. Leiomyomata of the uterus and the lung showed a reactivity against actin, desmin, estrogen- and progesteron receptor antigens. DNA analysis by CGH revealed a normal karyotype without evidence for an imbalanced loss or gain of DNA. Recurrent cytogenetic alterations are common in uterine leiomyomas, most often del (7)(q11.2-22q31-32) and t(12;14)(q14-15; q23-24). Leiomyosarcomas display diverse karyotypic abnormalities, most often involving chromosomes 1, 7, 13 and 14. Thus, the missing karyotypic imbalance in the presented case favors a pathogenesis which is different from usual leiomyomas as well as leiomyosarcomas.

Chromosome Aberrations↗
PubMed1998

Analysis of differential gene expression in human colorectal tumor tissues by RNA arbitrarily primed-PCR: a technical assessment.

RNA arbitrarily primed (RAP)-PCR is a powerful tool for studying differential gene expression in cancer cells. Systematic analysis of human tumor samples may provide a list of markers with potential application to the diagnosis, prognostic assessment, and treatment of the disease. Nevertheless, because of characteristics inherent to the samples and technique, artifactual results are likely. We have assessed the effects of several factors on RAP-PCR performance to determine the sensitivity and reproducibility of the technique, as well as the accuracy of its results, under different conditions in human cell lines and in a series of 129 paired human normal colonic mucosa-colorectal carcinoma samples. Our results show that RAP-PCR provides reliable fingerprints in a relatively wide spectrum of circumstances, including variations in RNA concentration and contamination by DNA. Densitometric analysis indicated that relative band-intensity variations more than 20% were reproducible in 95% of the cases. Serial analysis of paired normal-tumor cases yielded a number of bands that were recurrently either underexpressed or overexpressed in tumor relative to normal mucosa. These differentially expressed bands are prime targets of research because they represent candidate tumor-specific up- or down-regulated genes with a relevant role in carcinogenesis.

Colorectal Neoplasms↗
PubMed1998

[Beta-catenin expression and its significance for metastasis in curatively operated rectum carcinoma].

Two selected groups of 77 patients each (matched for age, sex, UICC stage and year of surgery) were compared. All patients were curatively operated on for rectal cancer by surgery alone. All remained locally disease-free, differing only in distant metachronous metastatic spread. beta-Catenin expression was investigated using immunohistochemical methods. Overexpression of nuclear beta-catenin was not correlated with disease-free survival or distant metachronous metastasis. Thus, this potential oncogen cannot be used as a prognostic marker in rectal cancer. Additionally, in four cases of intense nuclear staining, after DNA isolation and sequencing of exon 3, which encodes for the GSK-3 beta phosphorylation site, no mutations could be detected.

Biomarkers, Tumor↗
PubMed1997

Standardized characterization of gene expression in human colorectal epithelium by two-dimensional electrophoresis.

New diagnostic and prognostic markers are needed in colorectal cancer. They can be found by differential analysis at DNA, RNA or protein level. The accuracy of phenotypic comparisons of tumor and normal tissues depends on the purity of the samples. We present an effective method to identify and isolate proteins that are differentially expressed under altered conditions, and a two-dimensional reference protein map of the normal human colonic epithelium. Normal colonic mucosa, primary tumors and liver metastases were prepared in the operating room. After washing in an ice-cold medium containing protease inhibitors, crypts were isolated by mechanical preparation without using metalloproteinases. Epithelial cells were then selected using Ber-EP4 Dynabeads. The samples were denaturated before processing for immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis according to SWISS-2DPAGE standards. The samples contained more than 95% epithelial cells as confirmed by fluorescence-activated cell sorting using pan-anticytokeratin antibodies. Cell surfaces were not damaged, as assessed by scanning electronic microscope. A protein reference map of the normal colonic epithelium was defined. Using gel matching, N-terminal sequencing and/or immunoblotting techniques, 60 polypeptides - including proteins specifically expressed in colorectal epithelium - have now been identified. This reproducible method of sample preparation permits the comparison of protein patterns found in various pathological states with the present reference map (http://www.expasy.ch). Some of these patterns might provide diagnostic or prognostic markers, or even molecular targets for therapy in the future.

Colorectal Neoplasms↗
PubMed1997

[Concealed perforated aneurysm of an aberrant right hepatic artery: papillary bleeding. Case report and review of the literature].

A rare case of spurious aneurysm of an aberrant right hepatic artery is reported. Endoscopic retrograde cholangio-pancreaticography, computed tomography and selective angiography of the coeliac trunc are diagnostic. Resection of the aneurysm and interposition of saphenous vein is the preferred procedure. In selected cases ligation of the common hepatic artery is possible. Intrahepatic aneurysms are preferably treated interventionally.

Aged↗
PubMed1996

[Characterization of low molecular weight zinc species in normal commercial vegetable foodstuffs].

In six different ordinary vegetables, namely kohlrabi, Chinese cabbage, chard, leak, spinach and Jerusalem artichoke, zinc was mainly found as low molecular weight species. In the present study, these important zinc compounds are further investigated. The determinations of the metal are performed by ET-AAS. The zinc complexes of all vegetables are anionic at pH 8.0 and show similar elution behaviour in gel permeation and anion exchange chromatography. Consequently, a great resemblance in structure between the low molecular weight zinc species from the different vegetables can be supposed. Exemplary, the zinc complexes of kohlrabi and Chinese cabbage are further examined. In more purified samples of these vegetables compared to zinc neither stoichiometric amounts of free protein amino acids nor nicotianamine, free malic acid, citric acid or phytic acid have been detected. Mainly glutamic acid is found in molar excess to zinc after acid hydrolysis in both cases. The cysteine contents of both zinc-binding fractions are very low. Conclusively, the well-known gamma-glutamylcysteinyl-glycines (phytochelatines) can not be responsible for the bonding of zinc in both ordinary vegetables. We suppose that zinc in kohlrabi and Chinese cabbage is bound to a glutamic acid derivative unknown as yet, possibly a malic acid ester.

Amino Acid Sequence↗
PubMed1996

Radioiodination of nicotine with specific activity high enough for mapping nicotinic acetylcholine receptors.

A novel radiochemical method is presented to synthesize 5-[123I/125I/131I]-dL-nicotine by radioiodination of 5-bromonicotine. Radioiodination of the precursor 5-dL-bromonicotine was achieved using a copper (I)-assisted nucleophilic exchange reaction in the presence of reducing agent. The reaction conditions were optimized by varying pH, concentration of Sn(II) salt, ascorbic acid, Cu(I)chloride and reaction temperature. After purification by high-performance liquid chromatography the radiochemical purity of the product exceeded 98%, with a radiochemical yield of 55% and a specific activity > or =5 GBq/micromol. Specific binding of the iodinated nicotine was demonstrated in rat brain by autoradiography. The radioactivity from the specific structures was displaced by an excess of non-radioactive nicotine (10(-3)M) with KD and Bmax of 13.1+/-7.8 nM and 22+/-2.7 fmol/mg protein and unspecific binding of about 40%. The in vivo distribution of 5-[131I]iodonicotine was determined in 20 female Wistar rats at various time intervals of 15s to 90 min post injection (p.i.) by well counting and autoradiography. Brain activity peaked within 0.5 min p.i., and then showed a biexponential washout. Initially, activity within the cerebral cortex exceeded that of the cerebellum by a factor of 1.5-2.0. It was also increased in the striatum and thalamus. However, as soon as 15 min p.i. activity was almost homogeneously distributed. In conclusion, synthesis of 5-iodo-dL-nicotine (labelled with 131I, 125I or 123I, respectively) with appropriately high specific activity for receptor studies was achieved and specific binding to nicotine receptors in rat brain was demonstrated; following intravenous injection, however, there is considerable unspecific binding, obviously due to highly flow-dependent tissue retention.

Animals↗
PubMed1996

Concentration-effect relationship of the positive chronotropic and hypokalaemic effects of fenoterol in healthy women of childbearing age.

OBJECTIVE: To analyse fenoterol-induced tachycardia and hypokalaemia, the most important and most frequent adverse effects of tocolytic therapy with beta 2-adrenoceptor agonists in females of childbearing age. METHODS: The study was performed as a double blind, randomised, placebo controlled, cross over trial. Seven healthy women aged 22-38 y, received intravenous infusions of fenoterol at 3 different rates within the therapeutic range for tocolysis (0.5,1.0, and 2.0 micrograms.min-1) and placebo. The time courses of the plasma concentrations of fenoterol and potassium, and the heart rate were analysed with mixed effects pharmacokinetic-pharmacodynamic (PKPD) modeling using NONMEM. RESULTS: The plasma concentration-time course followed a linear two compartment model. Fenoterol-induced tachycardia was described by a linear concentration-effect model with baseline. The estimated baseline and slope parameters were 78 beats.min-1 and 0.032 beats.min-1.microgram-1.1, respectively. Fenoterol-induced hypokalaemia could be described by a physiological indirect response model including feedback; the Estimated basal plasma potassium concentration was 3.93 mmol.1-1 and the slope factor for the fenoterol-induced relative increase in the efflux of potassium from the extracellular space was 6.22*10(-4) ng.1(-1). CONCLUSION: The estimated population parameters permitted calculation of the expected time course of tachycardia and hypokalaemia in women after the initiation of tocolysis with fenoterol over the clinically relevant concentration range, and prediction of its variability. Based on simulation, our model predicted that a continuous infusion of 2.0 micrograms.min-1 (highest rate examined) would increase heart rate to 113 beats.min-1 at steady state and lower the plasma potassium concentration to 2.77 mmol.1(-1) 1.5 h after beginning the infusion. Thereafter, the plasma potassium concentration would slowly return to normal.

Adrenergic beta-Agonists↗
PubMed1996

Transthoracic bronchial intubation in a case of main bronchus disruption.

We report on a case of blunt thoracic trauma that resulted in complete disruption of the right main bronchus. Due to massive loss of respiratory volume during thoracotomy, sufficient ventilation could not be maintained via the orotracheal tube. Transthoracic intubation of the left main bronchus via the right bronchial defect was the ultima ratio procedure that allowed reanastomosis of the disrupted right main bronchus.

Bronchi↗
PubMed1995

Phenol and cresol metabolism in Bacillus pumilus isolated from contaminated groundwater.

From an aquifier contaminated with phenolic compounds seven bacterial strains able to grow on phenol and several mono- and disubstituted alkylphenols as sole source of carbon and energy were isolated. Five isolates belong to the genus Pseudomonas, two to the genus Bacillus. The isolate most active in utilization of the applied xenobiotics was identified as Bacillus pumilus and used for the investigation of the degradation pathways in liquid cultures. Cells of this strain precultured on phenol were able to utilize para-cresol as sole carbon source via the oxidation of the methylsubstituent and intradiol ring cleavage of the resulting protocatechuic acid, whereas an intradiol ring fission of the intermediate 4-methylcatechol led to 4-methylmuconolactone as dead end-product. Cells precultured on meta- and ortho-cresol were able to utilize the respective compounds as sole carbon sources via 3-methylcatechol, which induced the following extradiol ring fission pathway. Cells precultured on phenol were able to cooxidize meta- as well as ortho-cresol to 3-methylcatechol, which was cleaved via an intradiol ring fission, finally leading to the dead end-product 2-methylmuconolactone.

Bacillus↗
PubMed1995

[Selenium content of tea from different provinces of the People's Republic of China].

In the People's Republic of China there are wide regions where many people suffer from strong selenium deficiency. In order to elucidate the possibilities to compensate this state of need by the national drink, the selenium contents of 31 tea samples from nine provinces of the PR China were determined by hydride generation atomic absorption spectrometry (HG-AAS). The Se contents of the ten analyzed tea samples from one region with soils containing high selenium amounts range from 83 ng/g to 7530 ng/g. These results are in contrast to the Se contents of the remaining tea samples from other regions, which range from 28 to 573 ng/g. The extractable part of selenium in the tea drink ranges between 7% and 27% without significant difference among different tea samples. The accuracy of Se determination was tested by using one tea standard reference material. The daily consumption of one "Se tea" examined in this study assures that people who suffer from a Se deficiency resume enough of it. Drinking normal quantities of this tea an intoxication by Se is not to be expected.

China↗