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Biomedical subjects

M Lundin

Publications and source records attributed to M Lundin.

At least 19 recordsLinked to original sources
PubMed2006

Decreased xanthine oxidoreductase is a predictor of poor prognosis in early-stage gastric cancer.

BACKGROUND: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA and high-energy phosphates. About half of the patients with breast cancer have a decrease in XOR expression. Patients with breast cancer with unfavourable prognosis are independently identified by the loss of XOR. AIM: To assess the clinical relevance of XOR expression in gastric cancer. METHODS: XOR levels were studied by immunohistochemistry in tissue microarray specimens of 337 patients with gastric cancer and the relation between XOR expression and a series of clinicopathological variables, as well as disease-specific survival, was assessed. RESULTS: XOR was moderately decreased in 41% and was undetectable in another 14% of the tumours compared with the corresponding normal tissue. Decreased XOR was associated with advanced stage, deep tumour penetration, diffusely spread tumour location, positive lymph node status, large tumour size, non-curative disease, cellular aneuploidy, high S-phase fraction and high cyclooxygenase-2 expression, but not with p53 expression or Borrmann classification. Down regulation of XOR was associated with unfavourable outcome, and the cumulative 5-year gastric cancer-specific survival in patients with strong XOR expression was 47%, compared with 22% in those with moderate to negative expression (p<0.001). This was also true in patients with stage I-II (p = 0.01) and lymph node-negative (p = 0.02) disease, as well as in patients with smaller (< or =5 cm) tumours (p = 0.02). CONCLUSION: XOR expression in gastric cancer may be a new marker for a more aggressive gastric cancer biology, similar to that previously reported for breast cancer.

Adenocarcinoma↗
PubMed2005

Epithelial syndecan-1 expression is associated with stage and grade in colorectal cancer.

OBJECTIVES: Loss of epithelial heparan sulfate proteoglycan syndecan-1 has been associated with a more aggressive behavior in various cancer forms, but the prognostic significance of syndecan-1 expression in colorectal cancer is unclear. The aim of this study was to evaluate the prognostic value of immunohistochemical syndecan-1 expression in a series of 237 patients with colorectal cancer. METHODS: Paraffin-embedded formalin-fixed specimens were stained with a syndecan-1-specific monoclonal antibody, and both the epithelial and stromal expression were analyzed. RESULTS: Epithelial expression of syndecan-1 was seen in 222 tumors (94%), and it was associated with low stage of disease (p = 0.002) and low histological differentiation grade (p = 0.048). The cumulative 5-year survival of patients with weak and strong syndecan-1 expression was 49 and 54 %, respectively (p = 0.234). Syndecan-1 stromal immunoreactivity was observed in 138 tumors (58%), but lacked prognostic significance. Staining pattern and distribution can be viewed from digitized representative microscope slides (virtual slides) at http://www.webmicroscope.net/supplements/syndecan. CONCLUSIONS: The results are in line with previous reports in that low epithelial syndecan-1 expression was associated with a higher histological grade and a more advanced clinical stage of the patients. This study shows that syndecan-1 is expressed also in stromal tissue of colorectal cancer, but it does not support the proposed role of stromal syndecan-1 expression as a marker of poor clinical outcome.

Adult↗
PubMed2004

A digital atlas of breast histopathology: an application of web based virtual microscopy.

AIMS: To develop an educationally useful atlas of breast histopathology, using advanced web based virtual microscopy technology. METHODS: By using a robotic microscope and software adopted and modified from the aerial and satellite imaging industry, a virtual microscopy system was developed that allows fully automated slide scanning and image distribution via the internet. More than 150 slides were scanned at high resolution with an oil immersion x 40 objective (numerical aperture, 1.3) and archived on an image server residing in a high speed university network. RESULTS: A publicly available website was constructed, http://www.webmicroscope.net/breastatlas, which features a comprehensive virtual slide atlas of breast histopathology according to the World Health Organisation 2003 classification. Users can view any part of an entire specimen at any magnification within a standard web browser. The virtual slides are supplemented with concise textual descriptions, but can also be viewed without diagnostic information for self assessment of histopathology skills. CONCLUSIONS: Using the technology described here, it is feasible to develop clinically and educationally useful virtual microscopy applications. Web based virtual microscopy will probably become widely used at all levels in pathology teaching.

Breast↗
PubMed2003

Photoneutron yields from tungsten in the energy range of the giant dipole resonance.

Photoneutron production on the nuclei of high-Z components of medical accelerator heads can lead to a significant secondary dose during a course of bremsstrahlung radiotherapy. However, a quantitative evaluation of secondary neutron dose requires improved data on the photoreaction yields. These have been measured as a function of photon energy, neutron energy and neutron angle for natW, using tagged photons at the MAX-Lab photonuclear facility in Sweden. This work presents neutron yields for natW(gamma, n) and compares these with the predictions of the Monte Carlo code MCNP-GN, developed specifically to simulate photoneutron production at medical accelerators.

Monte Carlo Method↗
PubMed2003

Compton scattering from the deuteron and extracted neutron polarizabilities.

Differential cross sections for Compton scattering from the deuteron were measured at MAX-Lab for incident photon energies of 55 and 66 MeV at nominal laboratory angles of 45 degrees, 125 degrees, and 135 degrees. Tagged photons were scattered from liquid deuterium and detected in three NaI spectrometers. By comparing the data with theoretical calculations in the framework of a one-boson-exchange potential model, the sum and the difference of the isospin-averaged nucleon polarizabilities, alpha(N)+beta(N)=17.4+/-3.7 and alpha(N)-beta(N)=6.4+/-2.4 (in units of 10(-4) fm(3)), have been determined. By combining the latter with the global-averaged value for alpha(p)-beta(p) and using the predictions of the Baldin sum rule for the sum of the nucleon polarizabilities, we have obtained values for the neutron electric and magnetic polarizabilities of alpha(n)=8.8+/-2.4(total)+/-3.0(model) and beta(n)=6.5-/+2.4(total)-/+3.0(model), respectively.

Journal Article↗
PubMed2001

Tissue expression of human chorionic gonadotropin beta predicts outcome in colorectal cancer: a comparison with serum expression.

Production of the glycoprotein hormone human chorionic gonadotropin beta (hCGbeta) has been associated with more aggressive behavior in non-trophoblastic tumors. In this study, the prognostic value of immunohistochemical hCGbeta expression was evaluated in 239 patients with colorectal cancer. Paraffin-embedded, formalin-fixed specimens were stained with hCGbeta-specific monoclonal antibody, and the results were compared with serum levels determined with an assay based on the same antibody. hCGbeta immunoreactivity was seen in 52 of 239 tumors (22%). The difference in survival time between patients with histologically hCGbeta-negative (median survival 94 months) and -positive (median survival 27 months) tumors was statistically significant (p = 0.014). The risk ratio during follow-up for patients with positive hCGbeta tissue expression was 1.65 (95% CI 1.11-2.46). In a Cox multivariate analysis, Dukes' stage, hCGbeta and age remained independent prognostic factors. There was moderate agreement between immunohistochemical and serum expression levels of hCGbeta (kappa = 0.30). Using a combination of histological and serum levels of hCGbeta, the difference between survival rates was highly significant (p < 0.001). The accuracy when predicting 5-year survival status with the combined results of serum and tissue expression was 1.3% higher compared to hCGbeta tissue expression alone. Our results show that hCGbeta expression in both tumor tissue and serum has prognostic significance independent of other clinicopathological variables. Positive tumor staining does not always occur together with elevated serum levels, and the prognostic accuracy can slightly be increased by combining the results.

Adult↗
PubMed2001

Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer.

The prognostic value of the immunohistochemical expression of epithelial and stromal syndecan-1 was evaluated in 296 patients with gastric carcinoma. Formalin-fixed, paraffin-embedded specimens of gastric adenocarcinomas were stained with mouse monoclonal antibody B-B4 against human syndecan-1. Loss of immunoreactivity (syndecan-1 immunoreactivity correlated with a higher stage of disease (stages II-IV), tumour location in the upper third of the stomach, nodal metastases (N1 or N2), positive stromal syndecan-1 staining, deep tumour penetration (to subserosa or deeper = T2-T4), larger tumour size (> or = 5 cm) and intestinal type of cancer. No correlation between epithelial syndecan-1 immunoreactivity and age, gender, distant metastases, grade of differentiation or Borrmann classification was observed. Positive stromal syndecan-1 immunoreactivity correlated with decreased epithelial syndecan-1 expression, intestinal type of cancer and Borrmann type I. Patients with low epithelial syndecan-1 expression in cancer cells had worse overall survival than patients with strong epithelial syndecan-1 staining (p = 0.0012). Stromal syndecan-1-positive patients had a worse outcome than patients with syndecan-1-negative stroma (p = 0.0193). In Cox multivariate analysis, stromal syndecan-1 immunoreactivity was a prognostic factor independent of TNM stage, surgery for cure and tumour size. Thus, the immunohistochemical expression of syndecan-1 might be a predictor of outcome in patients with gastric adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Omission of histologic grading from clinical decision making may result in overuse of adjuvant therapies in breast cancer: results from a nationwide study.

PURPOSE: To investigate the influence of routinely performed histologic grading on breast cancer outcome prediction and patient selection for adjuvant therapy. PATIENTS AND METHODS: The analysis is based on a cohort of 2,842 women diagnosed with breast cancer and comprising 91% of all breast cancers diagnosed in five defined geographical regions in Finland in 1991 through 1992. Data on clinicopathologic factors and follow-up were collected from hospital case records and national registries. Histologic grade assessed at diagnosis and other clinicopathologic data were available for 1,554 operable unilateral invasive carcinomas. The relative value of grade with respect to competing prognostic factors was estimated with the Cox proportional hazards model and logistic regression. Interactions and nonlinearity of factors were accounted for by using an artificial neural network. RESULTS: Histologic grade was correlated strongly with survival in the entire series and in all subgroups studied. Women with well-differentiated node-negative cancer had a 97% 5-year distant disease-free survival rate as compared with 78% for women with poorly differentiated cancer. Grade was an independent prognostic factor in multivariate models and increased the predictive accuracy of a neural network model. Inclusion of grade data in a Cox multivariate model based on tumor size and hormone receptor status in node-negative cancer increased the proportion of patients with 5% or less risk for distant recurrence at 5 years from 15% to 54%. CONCLUSION: Even when assessed by pathologists who have no special training in breast cancer pathology, histologic grade has substantial and independent prognostic value in breast cancer. Omission of grading from clinical decision making may result in considerable overuse of adjuvant therapies.

Adult↗
PubMed2000

Gene Structure of the U2 snRNP-Specific A' Protein Gene from Salmo salar: Alternative Transcripts Observed.

The genomic sequence of the Atlantic salmon (Salmo salar) U2 snRNP-specific A' protein gene (U2A') was identified on a cosmid clone, and the exon/intron organization of a U2A' gene is described for the first time. The cosmid sequence includes 8 exons from which the 227 amino-terminal amino acids, of a total of 339 amino acids, are deduced. The cosmid cloning site was found in the 8th intron, which also contains a BglII minisatellite repeat region of unknown length. The 3' end of the gene was determined from a complementary DNA sequence. In the 234 amino-terminal amino acids the sequence identity is 84% to human and 49% to Arabidopsis thaliana. The phases of introns 1 to 8 are 1, 2, 0, 2, 0, 2, 0, and 1, respectively. The salmon U2A' gene was found by reverse transcription-polymerase chain reaction to be expressed in all 10 tissues tested, and in addition to the expected fragment of 695 bp, a smaller fragment of 615 bp was amplified in all tissues. Nucleotide sequencing of the fragments obtained showed that the smaller transcript lacks exon 6 and this results in frameshift of exon 7 and a truncated deduced polypeptide. This result may be explained by alternative splicing of the salmon U2A' gene. Different U2A' transcripts were found to exist also in human tissue.

Journal Article↗
PubMed1999

Distal pulse palpation: is it reliable?

The aim of this study was to evaluate the reliability of distal pulse palpation. The dorsalis pedis and the tibialis posterior arteries of 25 patients with suspected lower limb arterial disease were independently palpated by three vascular surgeons and three medical students in the outpatient clinic and by two vascular nurses and one physician in the vascular laboratory. The palpation findings were compared to the ankle/brachial index (ABI). Palpable and unpalpable pulses were best separated with ABI 0.76 as the cutoff point. The degree of misdiagnosis was unacceptably high, with an underdiagnosis of more than 30%. The agreement was highest (kappa 0. 68, good) among the vascular laboratory personnel in the peaceful vascular laboratory and lowest (kappa 0.38, fair) among the vascular surgeons in the busy outpatient clinic. The poor agreement and the high proportion of misdiagnosis obtained in the outpatient clinic argue against the use of pulse palpation as a single diagnostic method. Palpable pulses with low ABIs clearly state the need for more objective measurements whenever ischemia is suspected. Yet, by carefully palpating both pedal arteries under good, nonhurried conditions the reproducibility and accuracy of pulse palpation can be tolerable.

Adult↗
PubMed1999

Sialyl Tn is a frequently expressed antigen in colorectal cancer: No correlation with patient prognosis.

Immunohistochemical expression of sialyl Tn antigen (STn), previously claimed to be a prognostic factor in colorectal cancer, was evaluated in 239 patients with colorectal adenocarcinoma. Formalin-fixed, paraffin-embedded specimens were stained with the monoclonal antibody C1282. STn immunoreactivity was seen in 189 of 239 tumors (79%). There was no significant correlation between STn immunoreactivity and Dukes stage, tumor location, histological type or gender. However, STn was significantly more often expressed in younger patients. There was so significant difference in survival between STn-negative patients (median survival 68 months) and STn-positive patients (median survival 79 months). In a Cox multivariate analysis, Dukes stage was the strongest predictor of outcome, followed by the age of the patient, whereas STn did not provide any prognostic information.

Adenocarcinoma↗
PubMed1999

Artificial neural networks applied to survival prediction in breast cancer.

In this study, we evaluated the accuracy of a neural network in predicting 5-, 10- and 15-year breast-cancer-specific survival. A series of 951 breast cancer patients was divided into a training set of 651 and a validation set of 300 patients. Eight variables were entered as input to the network: tumor size, axillary nodal status, histological type, mitotic count, nuclear pleomorphism, tubule formation, tumor necrosis and age. The area under the ROC curve (AUC) was used as a measure of accuracy of the prediction models in generating survival estimates for the patients in the independent validation set. The AUC values of the neural network models for 5-, 10- and 15-year breast-cancer-specific survival were 0.909, 0.886 and 0.883, respectively. The corresponding AUC values for logistic regression were 0.897, 0.862 and 0.858. Axillary lymph node status (N0 vs. N+) predicted 5-year survival with a specificity of 71% and a sensitivity of 77%. The sensitivity of the neural network model was 91% at this specificity level. The rate of false predictions at 5 years was 82/300 for nodal status and 40/300 for the neural network. When nodal status was excluded from the neural network model, the rate of false predictions increased only to 49/300 (AUC 0. 877). An artificial neural network is very accurate in the 5-, 10- and 15-year breast-cancer-specific survival prediction. The consistently high accuracy over time and the good predictive performance of a network trained without information on nodal status demonstrate that neural networks can be important tools for cancer survival prediction.

Adult↗
PubMed1999

Short and long term outcome after laparoscopic cholecystectomy.

BACKGROUND: As an audit of patients undergoing laparoscopic cholecystectomy this study not only reports the short term results, but attempted to assess the long term effect of the operation on the symptom profiles of the patients. METHODS: Three hundred unselected consecutive patients underwent elective laparoscopic cholecystectomy from January 1991 to July 1994. Short term outcome was analysed by reviewing patient files for operation details, postoperative morbidity, complications, and gallbladder histology. Long term (median 2 years) outcome was evaluated by a detailed postal questionnaire. Symptomatic benefit ratios (BR) accruing from the laparoscopic removal of the gallbladder were calculated. RESULTS: Twelve operations (4.0%) were converted to open surgery and were excluded from long term outcome analyses. Median operation time was 93 (range 40-245) minutes. There were no deaths. Overall morbidity was 13 %. Median postoperative hospital stay was 2 days (range 1-18 days) and median time-off work 15 days (range 2-49 days). The overall response rate to the questionnaire was 87%. Only one of the 261 patients (0.4%) suffered from recurrent common bile duct stones so far. As shown by the benefit ratios the symptoms most effectively relieved by laparoscopic cholecystectomy were biliary pain (0.97), nausea (0.95), vomiting (0.96) and jaundice (0.94). Most patients with diarrhoea (0.70) and heartburn (0.66) felt relief. Constipation (0.39) and food intolerance (0.57) were unaffected. Most patients (90%) felt that the operation-initiating symptom had disappeared and 98 percent of the patients considered that they had obtained overall symptomatic improvement by the operation. CONCLUSIONS: Laparoscopic cholecystectomy appears to be a safe and effective way of treating the most common symptoms related to gallstone disease.

Adolescent↗
PubMed1998

Identification of a novel putative SINE sequence in a Salmo salar cosmid clone.

A novel putative SINE sequence was found in a randomly selected cosmid clone of Salmo salar. The sequence (cSSML032Alu, GenBank accession number: L77085) was found to have 78% identity in 212 bp, with one Salvelinus namaycush AluI satellite sequence (GenBank accession number: U27096) and 69% identity in 197 bp, with another AluI satellite sequence from S. namaycush (GenBank accession number: U27091). Colony hybridization of cSSML032Alu to a salmon cosmid library indicated its dispersed presence in the genome, with a copy number in the range of a few thousand. Direct terminal repeats of nine bases and a potential poly(A) tail remnant identified in the S. salar cSSML032Alu sequence indicate a possible ancient retroposon unit.

Journal Article↗
PubMed1997

Oncogenic point mutations induce altered conformation, redox sensitivity, and DNA binding in the minimal DNA binding domain of avian myeloblastosis virus v-Myb.

c-Myb is the founder member of a class of transcription factors with tryptophan-rich repeats responsible for DNA binding. Activated oncogenic forms of Myb are encoded by the avian retroviruses, avian myeloblastosis virus (AMV) and E26. AMV v-Myb encodes a truncated protein with 11 point mutations relative to c-Myb. The mutations in the DNA binding domain (DBD) were reported to impose distinct phenotypes of differentiation on transformed myeloid cells (Introna, M., Golay, J., Frampton, J., Nakano, T., Ness, S. A., and Graf, T. (1990) Cell 63, 1287-1297). The molecular mechanism operating has remained elusive since no change in sequence specificity has been found. We introduced AMV-specific point mutations in the minimal DBD of chicken c-Myb and studied their effect on structure and function of the purified protein. Fluorescence emission spectra and fluorescence quenching experiments showed that the AMV-specific point mutations had a significant effect on the conformation of the DBD, giving rise to a more compact structure, a change that was accompanied by a reduced sensitivity toward cysteine-specific alkylation and oxidation. The DNA binding properties were also altered by the AMV-specific point mutations, leading to protein-DNA complexes with highly reduced stability. This reduction in stability was, however, more severe with certain subtypes of binding sequences than with others. This differential behavior was also observed in an in vivo model system where DBD-VP16 fusions were coexpressed with various reporters. These findings imply that different subsets of Myb-responsive promoters may react differentially toward the AMV-specific mutations, a phenomenon that could contribute to the altered patterns of gene expression induced by the AMV v-Myb relative to wild type c-Myb.

Avian Myeloblastosis Virus↗
PubMed1997

Physical and linkage mapping of the bovine bone morphogenetic protein 1 on the evolutionary break region of BTA 8.

Bone morphogenetic protein 1 (BMP1) has been proposed as a regulatory molecule involved in the binding or activation of other BMP molecules. It has been described as being identical to the enzyme C-proteinase that processes procollagens to fibrillar collagens. A fragment containing an exon of the bovine BMP1 gene was amplified from an adapter-ligated genomic DNA library. The isolated bovine BMP1 fragment was assigned by fluorescence in situ hybridization (FISH) to bovine (BTA) chromosome 8q21, a region containing an evolutionary breakpoint between homology to human (HSA) chromosomes 8 and 9. The assignment to BTA 8 was confirmed by using a hybrid somatic cell panel. The 3' intron region of the amplified genomic BMP1 fragment showed a SSCP polymorphism, and linkage analysis in the International Bovine Reference Panel (IBRP) of families confirmed the boundary position of this gene. The BMP1 gene presents total linkage (theta = 0.00, Z = 3.61) with the lipoprotein lipase gene on BTA 8 and HSA 8 and a larger recombination fraction (theta = 0.11, Z = 5.03) with the marker GGTB2 on BTA 8 and HSA 9. Physical and genetic mapping of the bovine BMP1 gene contribute to narrow the boundary between the HSA 8 and HSA 9 homology segments on BTA 8 and to the comparative mapping between BTA 8, murine chromosome MMU 14, and HSA 8.

Animals↗