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Biomedical subjects

S Vilkki

Publications and source records attributed to S Vilkki.

15 recordsLinked to original sources
PubMed2002

Screening for microsatellite instability target genes in colorectal cancers.

BACKGROUND: Defects in the DNA repair system lead to genetic instability because replication errors are not corrected. This type of genetic instability is a key event in the malignant progression of HNPCC and a subset of sporadic colon cancers and mutation rates are particularly high at short repetitive sequences. Somatic deletions of coding mononucleotide repeats have been detected, for example, in the TGFbetaRII and BAX genes, and recently many novel target genes for microsatellite instability (MSI) have been proposed. Novel target genes are likely to be discovered in the future. More data should be created on background mutation rates in MSI tumours to evaluate mutation rates observed in the candidate target genes. METHODS: Mutation rates in 14 neutral intronic repeats were evaluated in MSI tumours. Bioinformatic searches combined with keywords related to cancer and tumour suppressor or CRC related gene homology were used to find new candidate MSI target genes. By comparison of mutation frequencies observed in intronic mononucleotide repeats versus exonic coding repeats of potential MSI target genes, the significance of the exonic mutations was estimated. RESULTS: As expected, the length of an intronic mononucleotide repeat correlated positively with the number of slippages for both G/C and A/T repeats (p=0.0020 and p=0.0012, respectively). BRCA1, CtBP1, and Rb1 associated CtIP and other candidates were found in a bioinformatic search combined with keywords related to cancer. Sequencing showed a significantly increased mutation rate in the exonic A9 repeat of CtIP (25/109=22.9%) as compared with similar intronic repeats (p< or =0.001). CONCLUSIONS: We propose a new candidate MSI target gene CtIP to be evaluated in further studies.

Colorectal Neoplasms↗
PubMed2001

Extensive somatic microsatellite mutations in normal human tissue.

Microsatellite (MS) instability occurs in tumors with DNA mismatch repair (MMR) deficiencies but is typically absent in adjacent normal tissue. However, MS mutations have been observed in normal tissues from rare individuals with congenital MMR deficiencies. Autopsy tissues from a 4-year-old with congenital MMR deficiency (MLH1-/-) were examined for MS mutations. Insertions and deletions were observed in CA-repeat MS loci. Approximately 0.26 to 1.4 mutations per MS locus per cell were estimated to be present in normal heart, lymph node, kidney, and bladder epithelium. These findings illustrate that phenotypically normal MMR-deficient cells commonly accumulate MS mutations. Loss of MMR and the accumulation of some MS mutations may occur early in MMR-deficient tumor progression, even before a gatekeeper mutation.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Expression of cyclooxygenase-2 in dysplasia of the stomach and in intestinal-type gastric adenocarcinoma.

PURPOSE: Cyclooxygenase (Cox) is the key enzyme in conversion of arachidonic acid to prostanoids. Two Cox genes have been cloned, and expression of Cox-2 mRNA and protein has been shown to be elevated in several human malignancies and in animal models of carcinogenesis. The purpose of this study was to investigate Cox-2 protein expression in human gastric dysplasias and adenocarcinomas. EXPERIMENTAL DESIGN: Performance of several Cox-2 antibodies was evaluated, after which Cox-2 protein expression was studied in 67 gastric cancer specimens and in eight definitive dysplasias by using immunohistochemistry. RESULTS: Cox-2 positivity was detected in 58% (25/43) of the intestinal-type (well-differentiated) tumors and 6% (1/18) of diffuse-type (poorly differentiated) tumors. Consistent with these data, we detected higher expression of Cox-2 mRNA, protein, and enzymatic activity in well-differentiated gastric cancer cell lines (MKN-28 and MKN-74) when compared with poorly differentiated cell lines (HSC-39 and KATO III). Cox-2 immunoreactivity was localized to the carcinoma cells, but the stroma of the tumors was negative. However, strong Cox-2 positivity was consistently detected in stromal cells at sites of erosions and ulcerations. Furthermore, four of nine (44%) definitive dysplasias of the stomach that showed no evidence of invasion were positive for Cox-2. CONCLUSIONS: Cox-2 is expressed by the neoplastic cells in the intestinal-type gastric adenocarcinoma and by precarcinogenic (dysplastic) lesions leading to this disease.

Adenocarcinoma↗
PubMed2000

Germline and somatic mutation analysis of MLH3 in MSI-positive colorectal cancer.

Microsatellite instability (MSI) is characteristic of hereditary nonpolyposis colorectal cancer, and occurs in a subset (10 to 15%) of unselected colorectal cancer cases. In hereditary nonpolyposis colorectal cancer, MSI is caused by defects in five mismatch repair genes, and in sporadic cases the main cause seems to be somatic MLH1 promoter methylation. Most likely additional hereditary nonpolyposis colorectal cancer genes remain to be discovered. Genes with simple repeats in their coding region are often targets for deletions in MSI-positive tumors. Several genes (TGFbeta RII, IGFIIR, MSH3, MSH6, BAX, MBD4) with significance in tumorigenesis harbor repeats in their coding regions and are often somatically inactivated because of deletions causing frameshifts. Recently, a novel human mismatch repair gene, MLH3, was cloned and shown to be involved in mammalian mismatch repair. To evaluate the possible role of MLH3 in hereditary cancer, we performed germline single-strand conformation polymorphism-analysis for 52 patients displaying features of inherited colorectal cancer. Forty-six of these had been diagnosed with MSI-positive tumors. No germline mutations were found. Similar to MSH3 and MSH6, MLH3 harbors mononucleotide repeats, ie, (A(6))-(A(9)), in its coding region, which makes it a putative target for somatic mutations in MSI-positive tumors. To evaluate its somatic inactivation we performed a deletion search focusing on eight exonic MLH3 mononucleotide repeats in a series of 93 MSI-positive tumors. Somatic deletions were found in 8.6% of the samples, a frequency similar to one detected in neutral noncoding mononucleotide repeats. No evidence of involvement of MLH3 in MSI tumorigenesis was obtained.

Amino Acid Substitution↗
PubMed1995

Anaesthesia for microvascular surgery in children. A combination of general anaesthesia and axillary plexus block.

Nowadays, microvascular reconstructions are performed with high success rate even in small children. The combination of general anaesthesia and axillary plexus block was used in this prospective study in order to achieve optimal surgical conditions in these challenging operations. Fifteen children under eight years of age (1-8 years) were anaesthetised with a standardised anaesthesia method using a combination of general anaesthesia and axillary plexus block for microvascular toe-to-hand transfer. The duration of anaesthesia varied between 7.5-14.5 hours (mean 11 h). The difference in peripheral skin temperature was used to indicate the difference in peripheral circulation. Due to plexus block, the mean skin temperature in the operated hand was 1.4 degrees C higher than in the opposite extremity at the end of the operation. In the early postoperative phase the temperature difference increased to 4.8 degrees C (P < 0.01) due to vasoconstriction in the control hand. The mean temperature in the transplant was 33.3 +/- 2.4 degrees C at the end of the operation. Primary microvascular results were good in all but two children who needed reoperations. All of the transfers survived. The mean central temperature increased progressively during the operation from 36.2 degrees C to 37.6 degrees C. One 1-year-old child developed a moderate hyperthermia of 39.1 degrees C. According to this study axillary plexus block can be combined with general anaesthesia in prolonged microvascular operations. When the effect of general anaesthesia ceased, the plexus block effectively increased peripheral circulation in the operated hand.

Anesthesia, General↗
PubMed1984

The need for replantation surgery after traumatic amputations of the upper extremity--an estimate based upon the epidemiology of Sweden.

Reports in the literature give different views of the frequency of serious amputation injuries of the upper extremity. In Sweden the vast majority of work injuries are registered by the Swedish Labour Market Insurance. All registered serious amputation injuries of the upper extremity in Sweden (8 million inhabitants) during 1979 were investigated in this study. For comparison the frequency of all amputation injuries (work and leisure) of the upper extremity in a county of Sweden (0.4 million inhabitants) during five years (1976-1980) were studied. The overall (work and leisure) incidence in Sweden is fourteen serious amputation injuries of the upper extremity per million inhabitants annually, i.e. a total number in the country of 110 cases per year. The frequency is lower in the areas of the largest cities and substantially higher in regions with sawmills, mechanical industry and/or agriculture. Thus, estimation of the total incidence based upon single counties or smaller regions may be misleading. Replantation would have been technically possible in more than 70% of the cases, but attempts at replantation were only carried out in less than 10% of the serious cases. This study emphasizes the importance of a referral of all patients with a suitable injury of the upper extremity to microsurgically trained handsurgeons.

Accidents, Occupational↗
PubMed1982

Toe to hand transfer.

Nine patients received a toe-to-finger transfer after accidental amputation and one after a congenital defect. One led to secondary amputation due to arterial thrombosis. Seven of the 9 patients would have the operation again if needed. Five transplants were great toe-to-thumb transfers which the authors feel superior to second toe to thumb transplantations. The method seems to be useful in reconstructive hand surgery.

Adolescent↗
PubMed1981

Arteriography before toe to hand free tissue transfer operation.

During the last two years the hand surgeons performed toe to hand transfer operations on eight patients. Preoperative hand and foot arteriography was carried out in all cases. This is important in order to determine which arteries can be used and which toe should be selected for the transfer. The great toe was transplanted in three patients and the second toe in five. In seven cases the operation was successful but in one the transferred second toe was lost. There was no difference between the diameters of the anastomosed arteries in the successful cases and in the failure, but the diameter of the digital artery in the latter was smaller than in the successful cases.

Adolescent↗
PubMedDate not supplied

Regional anesthesia for microvascular surgery: a combination of brachial plexus, spinal, and epidural blocks.

BACKGROUND AND OBJECTIVES: To evaluate the usefulness, safety, and efficacy of the combined plexus brachial, spinal, and epidural blocks in free toe to hand transplantations. METHODS DESIGN: Prospective, case series. SETTING: Tampere University Hospital, Finland. PATIENTS: Fifteen adult patients for toe to hand microvascular transplantation under combined regional anesthesia with bupivacaine. INTERVENTIONS: The efficacy of the blocks, complications, and patient satisfaction were recorded in the study form. MEASUREMENTS AND MAIN RESULTS: The duration of operations varied between 8 and 18 hours. No major complications occurred. Vasodilatation in the operated hand was maintained during the entire operation as well as in the postoperative period, and the surgical results were satisfactory. The mean skin temperature was 5 degrees C higher in the blocked extremity compared to the opposite hand. In every patient the skin temperature of the transplant was over 32.4 degrees C after the operation. Blood pressure, heart rate, temperature and oxygen saturation were well maintained during the entire procedure. All patients were satisfied with their anesthesia. Back pain occurred in 11 patients and in two it was considered severe. One patient may have had a systemic toxic reaction (shivering) due to high plasma levels of bupivacaine, but the symptom was transient. CONCLUSION: Combined regional anesthesia is an alternative to general anesthesia in prolonged microsurgical operations and it appears to improve perfusion of the transplanted extremity.

Adolescent↗