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Biomedical subjects

T Kirchhoff

Publications and source records attributed to T Kirchhoff.

At least 19 recordsLinked to original sources
PubMed2006

Accuracy of BRCA1 and BRCA2 founder mutation analysis in formalin-fixed and paraffin-embedded (FFPE) tissue.

BACKGROUND: A major limitation in counseling unaffected women from families with inherited breast and ovarian cancer is that a "true-negative" interpretation of wild type BRCA analysis of the proband cannot be inferred in the absence of demonstration of a BRCA mutation segregating in the kindred. Documentation of familial BRCA mutations from paraffin-derived DNA of deceased patients has been limited due to reports of technical complications leading to lack of reproducibility of BRCA testing of archival material. METHODS: DNA was extracted from formalin-fixed paraffin-embedded (FFPE) morphologically normal tissue of 161 blinded, coded samples from women previously genotyped for the three Ashkenazi Jewish BRCA founder mutations from lymphocyte-derived DNA. Multiplex PCR followed by denaturing polyacrylamide gel electrophoresis was performed for the three founder mutations to determine if analysis on FFPE tissue could produce results concordant with those of the lymphocyte-derived DNA. RESULTS: After disclosure of the sample codes, the results were compared with the original lymphocyte-derived DNA genotypes. Excluding one sample unevaluable due to PCR failure, there was 100% concordance of 160 genotypes (120 mutation samples) derived from DNA from archival FFPE tissue compared to peripheral lymphocytes. CONCLUSIONS: The method described reliably detected BRCA founder mutations in archival DNA derived from FFPE tissue. These results suggests that this technique may be useful in clinical settings to inform wild type BRCA results of unaffected probands, leading to avoidance of unnecessary intensified surveillance or risk-reducing surgery. With further validation this approach can also be applied to other populations where founder mutations are observed.

DNA↗
PubMed2005

Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. However, treatment options are limited and often inefficient. The aim of this study was to determine current survival rates for patients diagnosed with HCC and to identify prognostic factors, which will help in choosing optimal therapies for individual patients. A retrospective analysis of medical records was performed on 389 patients who were identified through the central tumour registry at our institution from 1998 to 2003. Clinical parameters, treatments received and survival curves from time of diagnosis were analysed. Overall median survival was 11 months. Liver cirrhosis was diagnosed in 80.5% of all patients. A total of 170 patients received transarterial chemoembolisation (TACE) and/or percutaneous ethanol injections (PEI) with a median survival rate of 16 months for patients receiving TACE, 11 months for patients receiving PEI and 24 months for patients receiving TACE followed by PEI. Independent negative prognostic parameters for survival were the presence of portal vein thrombosis, advanced liver cirrhosis (Child-Pugh score B or C) and a score of >2. This study will help to estimate survival rates for patients with HCC according to their clinical status at diagnosis and the treatments received.

Adolescent↗
PubMed2005

[Clinical application of the endolaryngeal laser measurement technique].

INTRODUCTION: Laser projection techniques have made morphometric measurement of laryngeal structures possible. The clinical application of a new laser measurement technique that uses a double reflecting mirror for laser beam duplication is discussed. MATERIAL AND METHODS: Endolaryngeal measurement with a new two-point laser light projection method was carried out on 25 patients with ten different organic lesions of the vocal folds. The laser measurement tool can be clipped onto the shaft of a rigid endoscope. A special software program enables quick and precise measurements of distances and areas that are in the same horizontal plane as the laser spots. FINDINGS: Using this new system, a clinical examination of the size of organic lesions of the vocal folds is possible, with a precise measurement of endolaryngeal structures being possible in all cases. The findings are easily documented, and the examinations can take place during routine laryngoscopic investigations. CONCLUSION: Systems for endolaryngeal measurements enable morphometric measurements within the larynx. Quantitative examinations have become possible in laryngology.

Endoscopy↗
PubMed2004

[Transcutaneous perianal ultrasound (PAUS) for the imaging of fistulas and abscesses in Crohn's disease].

Pelvic MRI and transanal ultrasound constitute the gold standard for the imaging of perianal inflammatory lesions in Crohn's disease. Perianal ultrasound (PAUS), however, is rarely considered in recent literature. In contrast to the established methods, perianal ultrasound represents an easy, cost-effective and at the same time sensitive method for the imaging of perianal abscesses and fistulas. This article illustrates the performance of perianal ultrasound and shows typical images of pathological findings such as abscesses and fistulas. PAUS is especially useful for acute diagnostics to rule out perianal abscesses and for follow-up evaluation of fistula treatment. For example, complications such as abscesses can be detected in a timely manner.

Abscess↗
PubMed2002

[Physical and technical elements of short-interval, color-filtered double strobe flash-stroboscopy].

INTRODUCTION: Quantitative measurement of vocal fold movements can be done either with high-speed imaging or with short interval, color-filtered double strobe flash-stroboscopy. The physical and technical elements of this new technique are described. METHODS: Two special strobe units (KAY Elemetrics RLS 9100) are used in a master-slave configuration. In this way an adjustable interval of 0.1-2.0 ms between flashes is introduced. The strobe flashes are color filtered and are separated by a brief interval. By this means a double exposure is created in each video frame.Real-time visualization of opening and closing velocities over the entire length of the vocal fold from anterior to posterior is possible. Quantification is possible off-line after image calibration. CONCLUSION: Short-interval, color-filtered double-strobe flash stroboscopy allows quantitative measurement of the velocity of vocal fold movements during vibration at different pitches and sound pressure levels (SPL). Images gained with this new technique provide information about a dynamic property (velocity) of the vocal fold within a single image.Therefore, its use could be helpful from the aspect of clinical documentation.

Artifacts↗
PubMed2002

The most frequent APC mutations among Slovak familial adenomatous polyposis patients. Adenomatous polyposis coli.

We screened 46 suspected families from whole Slovakia for familial adenomatous polyposis (FAP) cancer predisposition. Individuals were enrolled to the adenomatous polyposis coli (APC) gene mutations mapping program at the base of previous clinical investigation. We have used the following techniques: heteroduplex analysis (HDA), protein truncation test (PTT), single strand conformation polymorphism (SSCP) and sequencing for the identification and detailed positional analysis of APC mutations. Around 90% of all detected mutations were found being truncated. The most frequent mutations from this collection were located within codons 1309 and 1061 of exon 15 and represented 15% and 7%, respectively of all tested families. The expressive phenotype, large amount of colorectal polyps and congenital hypertrophy of the retinal pigment epithelium (CHRPE) were associated to all mutations within codons 1309 and 1060.

Adenomatous Polyposis Coli↗
PubMed2001

[Concepts for optimizing stent graft treatment of abdominal aortic aneurysms based on results of animal experiments].

PURPOSE: In the endoluminal therapy of abdominal aortic aneurysms, a short proximal aneurysm neck, endoleaks and the large size and stiffness of the introducer systems are responsible for many of the complications and sub-optimal outcomes. The purposes of the present review article is to to suggest strategies to minimize these complications based on the results of experimental studies in animals. MATERIAL AND METHODS: After implanting various types of stents across the renal artery origins, the functional and morphological changes in the kidneys and renal vessels were studied by various authors. In order to prevent progressive widening of the proximal aneurysmal neck and graft dislocation, Sonesson et al. performed a laparoscopic banding around the proximal neck in pigs. To study the effects of endoleaks, Marty, Schurink and Pitton carried out pressure measurements in experimental aneurysms with and without endoleaks. Sakaguchi und Pavcnik developed the "Twin-tube endografts" (TTEG) and the "Bifurcated drum occluder endografts" (BDOEG) and tested them in dogs. RESULTS: Up to 3 months after suprarenal stent placement, Chavan et al. detected no significant fall in the mean inulin clearance in sheep (140 +/- 46 ml/min before, 137 +/- 58 ml/min after). Nasim et al. and Malina et al. reported similar observations with respect to renal function. Suprarenal fixation may result in isolated thrombotic occlusions of the renal arteries and microinfarcts in the kidneys. Mean aortic diameters at the level of banding were significantly smaller in the animals with aortic banding as opposed to those in the control group without banding (8 mm vs 11 mm, p = 0.004). The banding caused a secure proximal fixation of the stent-graft. Persistent endoleaks resulted in significantly higher intraaneurysmal pressures. Although the TTEG and the BDOEG stent-grafts required smaller sheaths, occlusions were observed in 8% (TTEG) and 60% (BDOEG) of the graft limbs. DISCUSSION: Supra-renal fixation of the stent-graft does not significantly affect renal function. Depending partly on the stent-graft-Design, isolated microinfarcts in the kidneys or thrombotic occlusions of the renal arteries may occur. A laparoscopic banding of the aorta at the proximal neck after graft implantation could prevent widening of the proximal neck and graft dislocation with the passage of time. To reduce the incidence of endoleaks, embolization of large branches, particularly those arising from aneurysms without mural thrombus is advisable. Due to the relatively high rate of occlusion of the graft limbs, the TTEG and the BDOEG stent-graft designs still require refinement. A rational application of the results of these animal experimental studies in clinical practice could markedly improve the long-term results of endoluminal stent grafting of abdominal aortic aneurysms.

Aortic Dissection↗
PubMed2000

DNA polymerase lambda (Pol lambda), a novel eukaryotic DNA polymerase with a potential role in meiosis.

A new gene (POLL) encoding a novel DNA polymerase (Pol lambda) has been identified at mouse chromosome 19. Murine Pol lambda, consisting of 573 amino acid residues, has a 32% identity to Pol beta, involved in nuclear DNA repair in eukaryotic cells. It is interesting that Pol lambda contains all the critical residues involved in DNA binding, nucleotide binding and selection, and catalysis of DNA polymerization, that are conserved in Pol beta and other DNA polymerases belonging to family X. Murine Pol lambda, overproduced in Escherichia coli, displayed intrinsic DNA polymerase activity when assessed by in situ gel analysis. Pol lambda also conserves the critical residues of Pol beta required for its intrinsic deoxyribose phosphate lyase (dRPase) activity. The first 230 amino acid residues of Pol lambda, that have no counterpart in Pol beta, contain a BRCT domain, present in a variety of cell-cycle check-point control proteins responsive to DNA damage and proteins involved in DNA repair. Northern blotting, in situ hybridization analysis and immunostaining showed high levels of Pol lambda specifically expressed in testis, being developmentally regulated and mainly associated to pachytene spermatocytes. These first evidences, although indirect, suggest a potential role of Pol lambda in DNA repair synthesis associated with meiosis.

Amino Acid Sequence↗
PubMed2000

DNA polymerase mu (Pol mu), homologous to TdT, could act as a DNA mutator in eukaryotic cells.

A novel DNA polymerase has been identified in human cells. Human DNA polymerase mu (Pol mu), consisting of 494 amino acids, has 41% identity to terminal deoxynucleotidyltransferase (TdT). Human Pol mu, overproduced in Escherichia coli in a soluble form and purified to homogeneity, displays intrinsic terminal deoxynucleotidyltransferase activity and a strong preference for activating Mn(2+) ions. Interestingly, unlike TdT, the catalytic efficiency of polymerization carried out by Pol mu was enhanced by the presence of a template strand. Using activating Mg(2+) ions, template-enhanced polymerization was also template-directed, leading to the preferred insertion of complementary nucleotides, although with low discrimination values. In the presence of Mn(2+) ions, template-enhanced polymerization produced a random insertion of nucleotides. Northern-blotting and in situ analysis showed a preferential expression of Pol mu mRNA in peripheral lymphoid tissues. Moreover, a large proportion of the human expressed sequence tags corresponding to Pol mu, present in the databases, derived from germinal center B cells. Therefore, Pol mu is a good candidate to be the mutator polymerase responsible for somatic hyper- mutation of immunoglobulin genes.

Amino Acid Sequence↗
PubMed2000

Chemoembolization of hepatic metastases from intestinal neuroendocrine tumours.

Gastrointestinal neuroendocrine tumours, i.e. carcinoids and islet cell tumours, often metastasize diffusely into the liver, rendering complete surgical resection impossible. Unlike other malignancies, prolonged survival may occur even in advanced disease. Chemotherapy of these rare tumours is not only aimed at size reduction (objective response) but also at symptom reduction (biological response). Systemic therapy, using 5-fluorouracil, doxorubicin, cisplatin, cyclophosphamide, somatostatin-analogue, interferon or streptozotocin yielded response rates of up to 69%. Since neuroendocrine tumours are generally hypervascular locoregional chemotherapy and chemoembolization also have been used successfully. However, even though severe complications are rare, some degree of pain and the post-embolization syndrome are almost inevitably present. The expected therapeutic efficacy must be weighed against possible side effects. The best result that can be hoped for in the chemoembolization of intestinal neuroendocrine metastatic disease is, as yet, only palliation.

Antineoplastic Agents↗
PubMed2000

A double germline mutations in the APC and p53 genes.

Germline mutation in the APC gene is required for the initiation of the development of familial adenomatous polyposis (FAP). According to Fearon and Vogelstein model, further somatic mutations in the K-ras oncogene, DCC gene and p53 tumor suppressor gene are prerequisite for development of colon carcinoma. We have found that the germline mutations in the DNA isolated from lymphocytes of an 18 years old girl with extraordinary expressive phenotype in codons 1060-1061 of the APC gene result in truncation of the APC protein. The mutation in codons 12 and 13 of the K-ras oncogene was not detected, but another germline mutation was found in codon 210 of the p53 gene. Furthermore, no one of these germline mutations was detected in the DNA of peripheral blood lymphocytes of the patient's 21 years old healthy sister. Until now, there has been no evidence about the expressive phenotype due to mutation in codons 1060-1061 of the APC gene; the role of germline missense mutation in codon 210 of the p53 gene in the FAP malignant process remains to be elucidated too. The effect of the combination of germline mutation in two different tumor suppressor genes in the progress of disease is discussed.

Adenomatous Polyposis Coli↗
PubMed1999

Characterization of APC exon 15 germ-line mutation in FAP family with severe phenotype showing extracolonic symptoms.

The adenomatous polyposis coli (APC) gene plays a crucial role in colorectal carcinogenesis. Germ-line mutations of APC gene give rise to familial adenomatous polyposis coli (FAP) - autosomal dominant syndrome manifesting hundreds to thousands of colorectal polyps, if untreated with malignant progression. We have used the techniques of heteroduplex analysis (HDA), protein truncation test (PTT), single strand conformation polymorphism (SSCP) and DNA sequencing for the identification and detailed positional analysis of mutations in IFAP family with the expressive phenotype characterized by polyposis and extracolonic lesions. Detailed analysis revealed a 5bp deletion in a mutation cluster region (MCR) in exon 15 of APC gene in codon 1308. Two screened members of the FAP family exhibited this novel mutation.

Adenomatous Polyposis Coli↗
PubMed1998

Transarterial chemoembolization and percutaneous ethanol injection therapy in patients with hepatocellular carcinoma.

Both transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection therapy (PEI) have proven their efficacy in patients with unresectable hepatocellular carcinoma (HCC): TACE mainly in large lesions or disseminated disease and PEI in solitary lesions smaller than 3 cm. Although severe complications have been observed with both methods, their incidence is low. In 1991, the combination therapy of initial TACE followed by multiple sessions of PEI was introduced, allowing the repeated percutaneous treatment of lesions larger than 4 cm. This approach has been shown to be more effective than TACE alone in lesions up to 8 cm in diameter. An increased incidence of serious side-effects compared to either method alone has not been reported so far.

Carcinoma, Hepatocellular↗
PubMed1998

The combination of heteroduplex analysis and protein truncation test for exact detection of the APC gene mutations.

Familial adenomatous polyposis (FAP) is usually associated with mutation in the adenomatous polyposis coli (APC) gene. To examine the occurrence of these mutations in the number of FAP suspected families from the whole Slovakia effectively, we have applied heteroduplex analysis (HDA) and protein truncation test (PTT) for the analyses of 2-5 base pair deletions and point mutations of the APC gene. In the analyzed exon 15 of the APC gene determined by the primers 15Efor-15Grev for HDA and 15ET7-15J3 for PTT more than 70% of mutations should be deletions [3, 12], which are detectable by HDA. In our collection of 5 FAP families mutations in the APC gene were found in families 10, 27 and 41 using HDA. By PTT test the formation of truncated APC protein in FAP families 2, 10, 16 and 27 were revealed. The necessity of combination of at least HDA and PTT techniques for exact detection of APC mutations in analyzed APC region is discussed.

Adenomatous Polyposis Coli Protein↗
PubMed1997

Identification of APC exon 15 mutations in families suspected of familial adenomatous polyposis (FAP).

Patients with familial adenomatous polyposis coli (FAP) reveal numerous colorectal adenomas as well as benign and malignant extracolonic lesions. Adenomatous polyposis coli (APC) gene mutations are the crucial genetic defect in FAP. The APC mutation molecular analysis of 20 FAP families was performed using the novel and effective method of the heteroduplex analysis (HDA). All of these families were screened for mutations in APC exon 15. APC mutations were identified in 4 individuals of two families. These two families were also screened by the protein truncation test (PTT). The PTT results confirmed previous findings obtained by HDA. The results of molecular analysis were correlated with the clinical manifestations of extracolonic lesions and congenital hypertrophy of retinal pigment epithelium (CHRPE). Positive correlation of all clinical examinations and mutations of APC gene was observed in all 4 FAP patients.

Adenomatous Polyposis Coli↗
PubMed1996

Influence of human papillomavirus type 16 gene expression on in vitro differentiation of the human teratocarcinoma cell line 2102Ep.

Human papillomaviruses (HPVs) are known to infect human keratinocytes and cause alterations in epithelial differentiation. We showed in this study that expression of the HPV-16 genome was able to interfere with the in vitro differentiation of a human simple-epithelial cell type, the 2102Ep teratocarcinoma cell line. Stable HPV-16 genome-expressing 2102Ep cell lines were generated, and subsequent alterations in differentiation were analyzed in comparison with parental 2102Ep cells. We found that in 2102Ep cells phorbol ester-induced differentiation led to changes in the expression of SSEA antigens, whereas in HPV-transfected cell lines only minor changes were observed.

Antigens, Neoplasm↗