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Biomedical subjects

M Tomka

Publications and source records attributed to M Tomka.

At least 19 recordsLinked to original sources
PubMed2006

Ashkenazi founder BRCA1/BRCA2 mutations in Slovak hereditary breast and/or ovarian cancer families.

Germline mutations in BRCA1 and BRCA2 have been predominantly associated with the breast and ovarian cancers. Two mutations in BRCA1 (185delAG and 5382insC) and one mutation in BRCA2 (6174delT) are common in Ashkenazi Jewish population. To determine the proportion of these founder mutations, we analyzed DNA samples of 120 Slovak hereditary breast and/or ovarian cancer (HBOC) suspected families. Two particular exons of BRCA1 (2, 20) and 11N segment of BRCA2 were screened by single strand conformation polymorphism (SSCP) followed by DNA sequencing of fragments showing abnormal migration pattern. Mutational analysis revealed that 7 out of 20 (35%) families with detected BRCA1/BRCA2 pathogenic alteration harbored one of three Jewish mutations: five families with 5382insC, one family with 185delAG and one family with 6174delT. Interestingly, we have noted a very rare phenotype, when 5382insC in BRCA1 co-segregated also with endometrial carcinoma. Similarly to the studies from other countries of Central and Eastern Europe, the most frequent pathogenic alteration found was 5382insC that accounted for 1/4 of all gene defects detected. Following the high proportion of Ashkenazi Jewish founder mutations in Slovak HBOC families, a pre-screening for at least 5382insC mutation in individuals at even moderate risk would be appropriate.

Adult↗
PubMed2005

Cement embolization into the vena cava and pulmonal arteries after vertebroplasty: interdisciplinary management.

PURPOSE: To report interdisciplinary management in a case of cement embolization into the inferior vena cava and peripheral pulmonary arteries after percutaneous vertebroplasty. CASE REPORT: A 50-year-old female patient with an osteoporotic compression fracture of the second lumbar vertebra underwent percutaneous vertebroplasty with polymethylmetaacrylate. Thereafter, CT scanning revealed small asymptomatic cement emboli in peripheral pulmonary arteries, along with a hook-shaped cement fragment in the inferior vena cava. Due to the risk that the large cement fragment could migrate to the pulmonary arteries and cause serious complications, they were retrieved from the inferior vena cava by an endovascular technique and extracted through a surgical groin incision. The patient received anticoagulant treatment for 3 months and is free of complaints after 1 year. CONCLUSION: This case shows that this rare complication following vertebroplasty can be successfully managed with an interdisciplinary approach.

Bone Cements↗
PubMed2005

Surgical conversion of abdominal aortic stent-grafts--outcome and technical considerations.

OBJECTIVE: The purpose of this study was to evaluate the outcome of patients with stented abdominal aortic aneurysms who had to undergo open aneurysm repair with partial or total stent-graft removal. METHODS: Between October 1996 and December 2003, 117 patients with abdominal aortic aneurysms underwent endovascular repair. When open surgery was necessary during the initial and same anaesthesia as stent-graft implantation, it was defined as immediate conversion. When conversion was performed during a second anaesthesia, we defined it as late (acute or elective) conversion. RESULTS: A total of 33 patients underwent conversion to open surgery. In 7 (6%) patients, immediate conversion was necessary due to stent-graft misplacement and obstruction of the renal arteries (n=4), type Ia endoleaks (n=2) and stent-graft dislocation into the aneurysm sac (n=1). During a mean follow-up period of 39.6 months (min 0.03 months, max 80.4 months), 26 (23.6%) of the remaining 110 patients underwent late conversion to open surgery for endoleak (n=12), rupture (n=6), thrombosis (n=4), graft fatigue (n=2), aorto-duodenal fistula (n=1), and recurring peripheral embolisms (n=1). The mortality of acute conversion was 38% (5 of 13). Elective conversion did not lead to any mortality. CONCLUSION: Acute conversion of stented abdominal aortic aneurysms is associated with a high mortality. Elective stent-graft explantation with open aortic reconstruction is a safe but complex procedure.

Aged↗
PubMed2004

Femoral artery infection associated with a percutaneous arterial suture device.

This is a case report of a femoral artery infection with fatal outcome after using a percutaneous suture mediated closure device: A 77-year old patient underwent diagnostic angiography of his thoracic and abdominal aortic aneurysm, the puncture site was closed with the Perclose system. He developed a staphylococcal femoral artery infection with groin abscess, requiring surgical intervention with debridement and removal of the Perclose suture. After stent graft exclusion of the thoracic and abdominal aortic aneurysm a staphylococcal sepsis occurred and the patient died of aneurysm rupture months later despite long term antibiotic therapy. Since the use of the Perclose device carries an increased risk of femoral artery infection with septic endarteritis and bacteremia, it should not be used in routine diagnostic angiography.

Aged↗
PubMed2003

[Rupture of internal iliac artery aneurysm -- a rare cause of life-threatening rectal bleeding].

Isolated aneurysms of the iliac arteries are rare. Located deep in the lesser pelvis, they are diagnosed late or in a symptomatic stage. Because of their manifold anatomic relationships to pelvic structures, iliac aneurysms may cause different symptoms such as obstipation, hydronephrosis, venous thrombosis, and entrapment neuropathy. Aneurysm rupture is associated with high mortality. The rupture of an iliac aneurysm into the rectum with massive lower intestinal bleeding is extremely rare. We report a patient with 6-year follow-up after aneurysm resection, extra-anatomic bypass, and suture repair of the rectum with temporary colostomy.

Aged↗
PubMed2003

The novel exon 11 mutation of BRCA1 gene in a high-risk family.

Germline mutations in the BRCA1 and BRCA2 genes are required for the initiation of the development of hereditary forms of breast and ovarian cancer, which represent 10-15% of all cases. The course of the disease varies from case to case that can be due even to the possibility of multiple genetic changes including inactivation of other tumor suppressor genes--TP53 and APC genes or activation of oncogenes, especially K-ras oncogene. The combination of these changes results in an early expression of the broad variety of malignancies. The analyzed proband (II-5) comes from a high-risk family, in which various types of cancer were observed. The novel BRCA1 mutation in exon 11 (2057delCAGTGAAGAG) was detected by SSCP, HDA techniques and confirmed by automatic sequencing. The same deletion was observed in DNA sample of her first daughter (III-1), but DNA of her second one was without any mutational changes (III-2). Due to the occurrence of different types of cancer in this family, the incidental mutations in the APC; resp. TP53 tumor supressor genes and K-ras oncogene were searched as well. Any mutation was found after sequencing of SSCP interesting exons of these genes. The reasons for such strong malignant manifestation in this high risk family are discussed.

Amino Acid Sequence↗
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

Mutation screening of the BRCA1 gene in Slovak patients.

Breast cancer is the most commonly observed malignancy in women of the western world. The family history is the strongest risk factor for the disease. Two major genes, BRCA1 and BRCA2 that are involved in the familial breast and ovarian cancer have been described. Germ-line mutations of the BRCA1 gene have been linked to 85% of all hereditary breast and ovarian cancers. We performed a mutation screening ofthe entire codingregion of the BRCA1 gene in 29 Slovak families suspected of having inherited predisposition to breast cancer. For the analysis we used a combination of a single strand conformation polymorphism (SSCP), denaturing high-performance liquid chromatography (DHPLC) and sequencing. Genetic alterations were consistently indicated by SSCP and DHPLC and consequently confirmed by DNA sequencing as previously described pathogenic mutations. The patients with inherited BRCA1 mutations will undergo genetic counseling and cancer prevention health care program.

BRCA1 Protein↗
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

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↗
PubMed1989

Effects of substrate structure on the kinetics of circle opening reactions of the self-splicing intervening sequence from Tetrahymena thermophila: evidence for substrate and Mg2+ binding interactions.

The self-splicing intervening sequence from the precursor rRNA of Tetrahymena thermophila cyclizes to form a covalently closed circle. This circle can be reopened by reaction with oligonucleotides or water. The kinetics of circle opening as a function of substrate and Mg2+ concentrations have been measured for dCrU, rCdU, dCdT, and H2O addition. Comparisons with previous results for rCrU suggest: (1) the 2' OH of the 5' sugar of a dinucleoside phosphate is involved in substrate binding, and (2) the 2' OH of the 3' sugar of a dimer substrate is involved in Mg2+ binding. Evidently, the binding site for a required Mg2+ ion is dependent on both the ribozyme and the dimer substrate. The apparent activation energy and entropy for circle opening by hydrolysis are 31 kcal/mol and 50 eu, respectively. The large, positive activation entropy suggests a partial unfolding of the ribozyme is required for reaction.

Animals↗
PubMed1979

The first five years of the Budapest twin register, 1970-1974.

The Budapest Twin Register recorded 88.6% of the 1739 multiple births that occurred between 1970 and 1974. Of these, 31.2% were male-female pairs. Based on the examination of the placenta (19.8% monochorial) and of genetic makrers, 406 pairs proved to be monozygotic and 645 dizygotic. Sex ratio of twins at birth showed a female preponderance (1000 F: 1009 M) in comparison to singletons (1000 F: 1071 M). Average birthweight of the twins was 2101 g. The frequency of stillbirths was about four times higher in twins than in singletons, twice as high in monozygotic than in dizygotic twins, and 2.4 times higher among second than first-born twins.

Birth Weight↗