Alterations in the energy budget of Arctic benthic species exposed to oil-related compounds

We studied cellular energy allocation (CEA) in three Arctic benthic species (Gammarus setosus (Amphipoda), Onisimus litoralis (Amphipoda), and Liocyma fluctuosa (Bivalvia)) exposed to oil-related compounds. The CEA biomarker measures the energy budget of organisms by biochemically assessing changes in energy available (carbohydrates, protein and lipid content) and the integrated energy consumption (electron transport system activity (ETS) as the cellular aspect of respiration). Energy budget was measured in organisms subjected to water-accommodated fraction (WAF) of crude oil and drill cuttings (DC) to evaluate whether these compounds affect the energy metabolism of the test species. We observed significantly lower CEA values and higher ETS activity in G. setosus subjected to WAF treatment compared to controls (por=0.19). Different responses to oil-related compounds between the three test species are likely the result of differences in feeding and burrowing behavior and species-specific sensitivity to petroleum-related compounds.     

The development of subjective quality of life over the first 2 years in first-episode psychosis

The main aim of this study was to examine changes in subjective quality of life (general s-QoL) in patients with first-episode psychosis from baseline to 2 years follow-up. A total of 201 of 252 patients had full quality of life assessment at both baseline and at 2 years. Repeated measure analyses of variance were done to evaluate the development over time, and multiple linear regression analyses to evaluate predictors of change. These patients with a first-episode psychosis showed a significant improvement in general s-QoL during the first 2 years of treatment. Improvements in general s-QoL were associated with increase in excitative symptoms and with improvements in depressive symptoms, global functioning, level of daily activities, level of social activities, and perceived general health.     

Duodenogastric reflux increases the penetration of N-3H-methyl-N-nitro-N-nitrosoguanidine into the antral mucosa of rats: a possible role for mucosal erosions and increased cell proliferation in gastric carcinogenesis.

Duodenogastric reflux is a risk factor for gastric carcinogenesis, but the pathogenesis is not fully understood. We studied the risk of N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced carcinogenesis in the antrum of rats with duodenogastric reflux. Duodenal fluid was directed into the stomach through the pylorus (pyloric reflux group) or through a gastrojejunostomy (jejunal reflux group). After twenty-four weeks, 5-bromo-2-deoxyuridine (BrdU) was injected intravenously and the stomach was exposed to N-(3)H-methyl-N-nitro-N-nitrosoguanidine ((3)H-MNNG). The antral mucosa was examined with immunohistochemistry and autoradiography for identification of proliferating cells (BrdU labelled) and cells at risk of MNNG-induced carcinogenesis ((3)H-MNNG and BrdU-labelled cells). Duodenogastric reflux increased the number of double-labelled cells in the antral mucosa from 4.8 +/- 0.6 per mm in the control group to 11.3 +/- 1.9 in the jejunal reflux group (P < 0.05) and 12.7 +/- 0.9 in the pyloric reflux group (P < 0.05). Mucosal erosions were observed in 15 of 28 animals with pyloric reflux and the number of double-labelled cells in the erosion area (4.3 +/- 0.7) was higher than in the same area of animals without erosion (1.4 +/- 0.5) (P < 0.05). Duodeno-gastric reflux increased the cell proliferation and significantly changed the distance between the surface epithelial lining and the proliferating cells when compared to the controls. These results indicate that duodenogastric reflux increases the penetration of (3)H-MNNG into the antrum mucosa of rats. Increased cell proliferation and erosions increase the number of cells at risk of an initiation process from a penetrating gastric carcinogen.     

Association studies of a polymorphism in the Wilms' tumor 1 locus in norwegian patients with testicular cancer

One strategy for identifying genes involved in genetic predisposition to testicular germ-cell tumors (TC) is to perform association studies with polymorphic loci at or closely linked to candidate genes. Genes involved in normal fetal genital development, such as the Wilms' tumor 1 gene (WT1) located at 11p13, are among such candidates. The present study compares a TC (n = 442) and a control (n = 384) population for the allele frequencies of 2 polymorphic loci located at chromosome band 11p13. One of the polymorphisms (WT) was located within and the other (D11S325) in close proximity to the WT1 gene. No differences in allele frequencies between cancer patients and controls were found. However, the frequency of the A1 allele of the WT polymorphism was significantly increased in one of the cancer subgroups most likely to carry susceptibility genes (patients with bilateral cancer) compared to controls. Furthermore, the frequency of the A1 allele was increased in patients with metastatic disease. Such differences in allele frequencies were not observed for the D11S325 locus. The findings might indicate an involvement of the WT1 gene both in susceptibility to TC and in progression of the disease.     

Atrial fibrillation in rats induced by rapid transesophageal atrial pacing during brief episodes of asphyxia: a new in vivo model

Non-pharmacological in vivo models of atrial fibrillation (AF) have been developed in large animals only. We aimed to develop and characterize a new small animal non-pharmacological in vivo model of AF. AF was induced by transesophageal atrial burst pacing during 35 seconds periods of asphyxia in anesthetized male Sprague-Dawley rats. AF was reproducibly induced in 81% of the rats. The presence of AF was associated with an increased heart rate, and a decreased blood pressure. Treatment with amiodarone, D,L-sotalol, flecainide, and propranolol all reduced duration of AF, whereas verapamil treatment was associated with a marked profibrillatory effect. Increasing gap junction intracellular communication using the antiarrhythmic peptide analogue AAP10 did not affect AF duration. Basal plasma level of epinephrine and norepinephrine were increased 5- to 20-fold relative to values reported by others, but unchanged following 35 seconds of asphyxia. The results from our study demonstrate that the rat model shares several clinical key characteristics with human AF: (1) hemodynamic response to AF; (2) increased autonomic tone; (3) antiarrhythmic effects of clinically used drugs; (4) profibrillatory effect of verapamil. Relative to existing models of AF in larger animals, this model offers rapid, predictive, and inexpensive testing of antiarrhythmic/profibrillatory effects of new drugs.     

The female gender has a positive effect on survival independent of background life expectancy following surgical resection of primary non-small cell lung cancer: a study of absolute and relative survival over 15 years

Surgical resection is the treatment of choice for non-advanced lung cancer, but is encumbered with an overall relative poor long time prognosis. The purpose of this study was to examine if long time survival for patients operated for non-small cell lung cancer have changed over a 15 years period. We retrospectively studied hospital records of the 351 patients operated, with the intention to cure, for a primary non-small cell carcinoma (NSCLC) in our department between 1 January 1988 and 31 December 2002. Preoperative clinical variables were noted together with variables allowing staging based on pathological examination. Absolute survival and survival relative to expected was studied for the whole group using uni- and multivariate Cox analyses. Early 30 days mortality was 2.0%. The 5-year absolute and relative survivals for all patients were 46.3% and 52.6%, respectively. After 10 years corresponding values were 32.9% and 44.6%. At the end of the study, the 15-year absolute survival was 27.8% with a relative survival of 46.2%. Univariate analysis revealed that age, gender, nodular stage, tumour size, p-stage, type of resection, time of operation and additional cardiovascular disease at the time of operation significantly influenced survival. Multivariate analysis for all patients revealed that low age, female gender, low nodular stage, and operation late in the study period were significant prognostic factors predicting improved survival. When including a population based age- and gender-adjusted median expected life time for every patient as a predictor for survival, only female gender and low nodular stage were additional significant and independent positive prognostic factors.     

Immunohistochemistry identifies carriers of mismatch repair gene defects causing hereditary nonpolyposis colorectal cancer.

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by mutations in mismatch repair (MMR) genes. The aim of this study was to validate immunohistochemistry and family history as prescreening tools to predict germline mutations in MLH1, MSH2, and MSH6. PATIENTS AND METHODS: Pedigrees from 250 families were extended, cancer diagnoses were verified, and families were classified according to the Amsterdam and the Bethesda criteria. Tumor specimens were examined with immunohistochemistry for the presence of MLH1, MSH2, and MSH6 proteins. Mutation analyses were performed in blood samples from the same patients. RESULTS: Blood samples from affected index persons in 181 families and tumor specimens from 127 of the affected index persons were obtained. Thirty tumors lacked one or more gene products. Sensitivity of immunohistochemistry to detect mutation carriers was 100%, specificity was 82%, and positive predictive value was 85%. Sensitivities, specificities, and positive predictive values for the Amsterdam criteria were 82%, 8%, and 45%, respectively, and for the Bethesda criteria were 100%, 0%, and 48%, respectively. Distribution of mutations was MLH1 = 4, MSH2 = 11, and MSH6 = 4. CONCLUSION: Wide clinical criteria to select HNPCC kindreds, followed by immunohistochemistry of tumor material from one affected person in each family, had high sensitivity and specificity to predict MMR mutations.     

Macrophage scavenger receptor 1 999C>T (R293X) mutation and risk of prostate cancer.

BACKGROUND: Variants in the gene encoding the macrophage scavenger receptor 1 (MSR1(4)) protein have been identified in men with prostate cancer, and several small studies have suggested that the 999C>T (R293X) protein-truncating mutation may be associated with an increased risk for this disease. METHODS: Using large case-control, cohort, and prostate cancer family studies conducted in several Western countries, we tested for the 999C>T mutation in 2,943 men with invasive prostate carcinoma, including 401 males from multiple-case families, 1,982 cases unselected for age, and 575 men diagnosed before the age of 56 years, and in 2,870 male controls. Risk ratios were estimated by unconditional logistic regression adjusting for country and by a modified segregation analysis. A meta-analysis was conducted pooling our data with published data. RESULTS: The prevalence of MSR1*999C>T mutation carriers was 0.027 (SE, 0.003) in cases and 0.022 (SE, 0.002) in controls, and did not differ by country, ethnicity, or source. The adjusted risk ratio for prostate cancer associated with being a 999C>T carrier was 1.31 [95% confidence interval (CI), 0.93-1.84; P = 0.16]. The modified segregation analysis estimated the risk ratio to be 1.20 (95% CI, 0.87-1.66; P = 0.16). The risk ratio estimated from the meta-analysis was 1.34 (95% CI, 0.94-1.89; P = 0.10). CONCLUSION: Our large-scale analysis of case and controls from several countries found no evidence that the 999C>T mutation is associated with increased risk of prostate cancer. The meta-analysis suggests it is unlikely that this mutation confers more than a 2-fold increased risk.