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Biomedical subjects

E Brun

Publications and source records attributed to E Brun.

At least 19 recordsLinked to original sources
PubMed2004

Lymph node metastasis in epithelial malignancies of the appendix with peritoneal dissemination does not reduce survival in patients treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy.

BACKGROUND: Peritoneal dissemination of appendiceal malignancy combined with regional lymph node metastasis is an unusual combination of patterns of cancer dissemination. METHODS: A database of 501 appendiceal malignancy patients, all with documented peritoneal seeding, was used to identify 25 patients with involvement of the regional lymph nodes. All patients were uniformly treated with cytoreductive surgery plus perioperative intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil. The clinical and pathologic features of the lymph node-positive patients were compared with those of the lymph node-negative patients. The effect of regional lymph node involvement on survival was determined. Within the group of lymph node-positive patients, clinical and pathologic features were tested for their effect on survival. RESULTS: When compared with patients with no apparent lymph node positivity, patients with positive lymph nodes were more likely to have an acute abdomen as the initial presentation (P < .001). The intestinal (nonmucinous) histological type was more common (P < .001), and the disseminated peritoneal adenomucinosis histology was less common (P < .001). Survival with the aggressive treatment strategy used in these patients was not different for lymph node-positive as compared with lymph node-negative patients (P = .15 by univariate and P = .38 by multivariate analysis). CONCLUSIONS: Appendiceal malignancy with dissemination to the lymph nodes has a more acute onset and a more frequent nonmucinous histology. With aggressive treatment strategies, lymph node-positive patients did not show a statistically significantly diminished survival.

Acute Disease↗
PubMed2003

Risk of inter-river transmission of Gyrodactylus salaris by migrating Atlantic salmon smolts, estimated by Monte Carlo simulation.

The possibility of Gyrodactylus salaris infection of wild North Atlantic salmon Salmo salar spreading to new rivers poses a major threat in Norway. This freshwater parasite can survive for some time in brackish water, and it has been suggested that smolts leaving infected rivers could transport vital parasites to new rivers. A Monte Carlo simulation model was used to estimate the risk that infected smolts would ascend a new river. Data from an infected watercourse in Norway, where the salmon population is maintained constant by cultivation, were used. The model included information on prevalence of infection, hydrographical conditions, survival of G. salaris in brackish water, fish population characteristics, and smolt behaviour during seaward migration. The annual risk was estimated for 3 neighbouring rivers situated at different distances from the index river. For the nearest river, which shares the same brackish water zone with the index river, the model estimated an annual risk of 31% that at least 1 infected smolt would ascend this river. The results of the simulation were highly sensitive to the water salinity along the migration route. For the other rivers, the annual risk was lower than 0.5%. Risk was positively correlated with the number of fish leaving the index river, indicating control of this number as a possible tool in risk management.

Animal Migration↗
PubMed2003

Cardiomyopathy syndrome in farmed Atlantic salmon Salmo salar: occurrence and direct financial losses for Norwegian aquaculture.

Cardiomyopathy syndrome (CMS) was first diagnosed in the mid-1980s in farmed Atlantic salmon in Norway, and later also in Scotland and the Faeroe Islands. In Norway the number of diagnosed cases increased from 25 to 103 in the period from 1998 to 2001 according to the National Veterinary Institute (NVI) records. Very little is known about the causes of the disease and there is no documentation of its impact on the farmed salmon industry. This field survey was performed to collect information on occurrence, risk factors and the economic importance of CMS in sea farmed Atlantic salmon Salmo salar in Norway. Data were collected in January 2001 from a total of 174 groups of farmed salmon which had been previously transferred to sea during 1999 and 2000. Approximately 11.5% of all groups of salmon in our study experienced cases of CMS. Affected fish were presumably in generally good condition prior to time of death. In fish which had completed the seawater production cycle, CMS occurred more than 1 yr (median 395 d, >2 kg body weight) after seawater transfer. In fish transferred into the sea during autumn 2000 which had not completed the seawater cycle during the study period, CMS was diagnosed at a weight as low as 700 g. Although sudden death is characteristic, CMS may be regarded as a chronic disease, with moderately elevated mortality rates at site level. Affected groups showed significantly increased mortality, causing a direct annual financial loss for the industry of Euros 4.5 to 8.8 million on fish farms. Preventive prescheduled slaughtering of salmon, which is performed on many affected farms, may be too costly when done too early.

Animals↗
PubMed2003

Body mass index and the risk of mortality in type II diabetic patients from Verona.

OBJECTIVE: The relation between body weight and mortality in type II diabetic patients has not been fully elucidated. The aim of the present study was to evaluate the impact of body weight on mortality in a well-characterized type II diabetic cohort. RESEARCH DESIGN AND METHODS: We examined a cohort of 3398 type II diabetic patients, alive on December 1986 and followed up for 10 years, to assess mortality and its causes and to investigate the relationship between body mass index (BMI) and mortality from all and specific causes. For this purpose, survival in the different quartiles of BMI was evaluated by a Cox model, controlling for sex, age, treatment, smoking, duration of diabetes, hypertension, and fasting plasma glucose. The Cox model was applied either excluding (model 1) or including (model 2) the last three variables. RESULTS: During the 10 ys of follow-up, 1212 deaths (639 women, 573 men) occurred in the cohort under study. Since the interaction between BMI and age was statistically significant (P = 0.002), survival was studied separately in people aged <65 and > or =65 y (median age of the cohort = 65.9 y). Under 65 y, a significantly higher all-cause mortality was observed in obese patients, that is, in the IV quartile (BMI> or =30.9 kg/m(2); RR = 1.74; CI 95% = 1.26-2.40), in model 1. The inclusion of hypertension, duration of diabetes, and fasting plasma glucose in the model (model 2) slightly decreased the relative risk (RR = 1.52; CI 95% = 1.10-2.11). After 65 y, higher body weight was associated with a better outcome, especially in patients belonging to the IV quartile of BMI (RR = 0.74; CI 95% = 0.62-0.90). CONCLUSIONS: In older type II diabetic patients, a moderate excess weight predicts a better survival, while obesity is a negative prognostic factor in patients younger than 65 y. In the latter patients, the effect of obesity on mortality seems to be partly mediated by hypertension, duration of diabetes, and fasting plasma glucose.

Adult↗
PubMed2001

Prognostic value of histopathological response to radiotherapy and microvessel density in oral squamous cell carcinomas.

The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.

Adult↗
PubMed2001

Cyclin D1 overexpression versus response to induction chemotherapy in squamous cell carcinoma of the head and neck--preliminary report.

The aim of this study was to investigate whether there is an association between overexpression of cyclin D1 and response to therapy. Immunohistochemical overexpression of cyclin D1 was determined in paraffin-embedded specimens from diagnostic biopsies of 89 primary cases of squamous cell carcinoma of the head and neck (SCCHN), using a polyclonal antiserum. The tumor response rates were estimated after curative treatment (i.e. surgery and/or radiotherapy and/or chemotherapy). Patients whose tumors were overexpressing cyclin D1 showed complete or partial response to neoadjuvant chemotherapy with cisplatin/5-FU. In addition, a majority of cyclin D1 negative tumors did not respond at all to this treatment (p = 0.02, Fisher's exact test). This study indicates that immunohistochemical assessment of cyclin D1 expression in SCCHN could be a new predictive marker to select a subgroup of patients that will benefit from neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Serum chemistry of the minke whale from the northeastern Atlantic.

Serum samples were collected from 42 harpooned minke whales (Balaenoptera acutorostrata) during commercial whaling off the coast of northern Norway (1997 and 1998) and analyzed for serum chemistry parameters in order to find clinical reference values for the northeastern Atlantic stock of this species. Mean and median values, as well as standard deviation and 90% central range, are presented for 28 different serum chemistry parameters. Lipemia is a common finding in marine mammals such as the minke whale, and chemical analysis of lipemic serum samples may produce artifacts. We found statistically significant elevated values of total protein, globulin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), sodium and chloride in strongly-lipemic compared to non-lipemic samples, all which may be artifacts due to interference of lipids with the methods used for analysis. In addition, we found significantly elevated levels of creatin kinase, lactate dehydrogenase (LDH), urea, uric acid and triglycerides, as well as a decrease in creatinine in the strongly lipemic samples. Reanalyzing serum samples after twelve mo storage at -20 C (n = 13) revealed reduction in the serum concentration of the enzymes ALT (42%), alkaline phosphatase (ALP; 10%), LDH (19%), gamma glutamyl transferase (17%) and amylase (11%), as well as for triglycerides (9%) and non-esterified fatty acids (16%). It is crucial that serum chemistry analysis is performed without delay after sampling. Possible changes in the values of some parameters due to the presence of high amounts of lipids or long term storage of samples must be considered when interpreting results from serum chemistry analysis in these animals.

Alanine Transaminase↗
PubMed2000

Alteration of a single tryptophan residue of the cellulose-binding domain blocks secretion of the Erwinia chrysanthemi Cel5 cellulase (ex-EGZ) via the type II system.

Cel5 (formerly known as endoglucanase Z) of Erwinia chrysanthemi is secreted by the Out type II pathway. Previous studies have shown that the catalytic domain (CD), linker region (LR) and cellulose-binding domain (CBD) each contain information needed for secretion. The aim of this work was to further investigate the secretion-related information present in the CBD(Cel5). Firstly(, )deleting a surface-exposed flexible loop had no effect on secretion. This indicated that some structural freedom is tolerated by the type II system. Secondly, mutation of a single tryptophan residue, previously shown to be important for binding to cellulose, i.e. Trp43, was found also to impair secretion. This indicated that the flat cellulose-binding surface of CBD(Cel5 )contains secretion-related information. Thirdly, CBD(Cel5) was substituted by the CBD(EGG) of Alteromonas haloplanctis endoglucanase G, yielding a hybrid protein CD(Cel5)-LR(Cel5)-CBD(EGG) that exhibited 90 % identity with Cel5, including the Trp43 residue. The hybrid protein was not secreted. This indicated that the Trp43 residue is necessary but not sufficient for secretion. Here we propose a model in which the secretion of Cel5 involves a transient intramolecular interaction between the cellulose-binding surface of CBD(Cel5) and a region close to the entry into the active site in CD(Cel5). Once secreted, the protein may then open out to allow the cellulose-binding surface of CBD(Cel5 )to interact with the surface of the cellulose substrate. An implication of this model is that protein molecules fold to a specific secretion-competent conformation prior to secretion that is different from the folding state of the secreted species.

Amino Acid Substitution↗
PubMed2000

Binding site analysis of cellulose binding domain CBD(N1) from endoglucanse C of Cellulomonas fimi by site-directed mutagenesis.

Endoglucanase C (CenC), a beta1,4 glucanase from the soil bacterium Cellulomonas fimi, binds to amorphous cellulose via two homologous cellulose binding domains, termed CBD(N1) and CBD(N2). In this work, the contributions of 10 amino acids within the binding cleft of CBD(N1) were evaluated by single site-directed mutations to alanine residues. Each isolated domain containing a single mutation was analyzed for binding to an insoluble amorphous preparation of cellulose, phosphoric acid swollen Avicel (PASA), and to a soluble glucopyranoside polymer, barley beta-glucan. The effect of any given mutation on CBD binding was similar for both substrates, suggesting that the mechanism of binding to soluble and insoluble substrates is the same. Tyrosines 19 and 85 were essential for tight binding by CBD(N1) as their replacement by alanine results in affinity decrements of approximately 100-fold on PASA, barley beta-glucan, and soluble cellooligosaccharides. The tertiary structures of unbound Y19A and Y85A were assessed by heteronuclear single quantum coherence (HSQC) spectroscopy. These studies indicated that the structures of both mutants were perturbed but that all perturbations are very near to the site of mutation.

Alanine↗
PubMed2000

Structure and binding specificity of the second N-terminal cellulose-binding domain from Cellulomonas fimi endoglucanase C.

The 1,4-beta-glucanase CenC from Cellulomonas fimi contains two cellulose-binding domains, CBD(N1) and CBD(N2), arranged in tandem at its N-terminus. These homologous CBDs are distinct in their selectivity for binding amorphous and not crystalline cellulose. Multidimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy was used to determine the tertiary structure of CBD(N2) in the presence of saturating amounts of cellopentaose. A total of 1996 experimental restraints were used to calculate an ensemble of 21 final structures for the protein. CBD(Nu2) is composed of 11 beta-strands, folded into two antiparallel beta-sheets, with a topology of a jellyroll beta-sandwich. On the basis of patterns of chemical shift perturbations accompanying the addition of cellooligosaccharides, as well as the observation of intermolecular protein-sugar NOE interactions, the cellulose-binding site of CBD(N2) was identified as a cleft that lies across one face of the beta-sandwich. The thermodynamic basis for the binding of cellooligosaccharides was investigated using isothermal titration calorimetry and NMR spectroscopy. Binding is enthalpically driven and consistent with a structural model involving hydrogen bonding between the equatorial hydroxyls of the glucopyranosyl rings and polar amino acid side chains lining the CBD(N2) cleft. Affinity electrophoresis was used to determine that CBD(N2) also binds soluble beta-1,4-linked polymers of glucose, including hydroxyethylcellulose and beta-1,3-1,4-glucans. This study complements a previous analysis of CBD(N1) [Johnson, P. E., Joshi, M. D., Tomme, P., Kilburn, D. G., and McIntosh, L. P. (1996) Biochemistry 35, 14381-14394] and demonstrates that the homologous CBDs from CenC share very similar structures and sugar binding properties.

Actinomycetales↗
PubMed2000

Fasting plasma glucose variability predicts 10-year survival of type 2 diabetic patients: the Verona Diabetes Study.

OBJECTIVE: In the present study, we evaluated whether the coefficient of variation (CV) of fasting plasma glucose (FPG) over a 3-year period was a significant predictor of mortality in type 2 diabetic patients aged 56-74 years. RESEARCH DESIGN AND METHODS: All type 2 diabetic patients (n = 1,409) aged 56-74 years attending the Verona Diabetes Clinic and having at least two FPG determinations in each of the years 1984-1986 were followed for 10 years (1987-1996) to assess total and cause-specific mortality Patients were grouped into tertiles of mean and CV of FPG during 1984-1986. These parameters as well as sex, age, diabetes duration, insulin treatment, smoking, hypertension, and hypercholesterolemia were included in multivariate survival analyses. RESULTS: During the follow-up, 468 patients died. The CV of FPG was an independent predictor of total, cardiovascular, and cancer mortality. Mean FPG was a predictor of total mortality only when the CV of FPG was not included in the analyses. CONCLUSIONS: Long-term variability of fasting glucose is an independent predictor of mortality in patients with type 2 diabetes. The CV of FPG might be considered a useful additional parameter in the management of these patients.

Aged↗
PubMed2000

Diabetes duration and cause-specific mortality in the Verona Diabetes Study.

OBJECTIVE: To examine the 10-year mortality and effect of diabetes duration on overall and cause-specific mortality in diabetic subjects in the Verona Diabetes Study (VDS). RESEARCH DESIGN AND METHODS: Records from diabetes clinics, family physicians, and a drug consumption database were used to identify 5,818 subjects > or =45 years of age with type 2 diabetes who were alive and residing in Verona, Italy on 31 December 1986. Vital status of each subject was ascertained on 31 December 1996. Underlying causes of death were determined from death certificates. Death rates and death rate ratios (DRRs) were computed and standardized to the population of Verona in 1991. RESULTS: During the study, 2,328 subjects died; 974 deaths were attributable to cardiovascular disease, 517 to neoplasms, 324 to diabetes-related diseases, 134 to digestive diseases, 250 to other natural causes, and 48 to external causes. There were 81 subjects who died of unknown causes. Death rates from natural causes were higher in men than in women (DRR 1.4, 95% CI 1.2-1.5) and rose in both sexes with increasing duration of diabetes (P = 0.001). Among the natural causes of death, those for diabetes-related diseases were strongly related to diabetes duration (P = 0.001). a modest relationship with duration was also found for ischemic heart disease in men (P = 0.07). CONCLUSIONS: Cardiovascular disease was the principal cause of death among people with type 2 diabetes in the VDS. Rates for natural causes of death rose with increasing duration of diabetes. Deaths from diabetes-related diseases in both sexes and from ischemic heart disease in men were largely responsible for this increase.

Adolescent↗
PubMed1999

The cellulose-binding domains from Cellulomonas fimi beta-1, 4-glucanase CenC bind nitroxide spin-labeled cellooligosaccharides in multiple orientations.

The N-terminal cellulose-binding domains CBDN1 and CBDN2 from Cellulomonas fimi cellulase CenC each adopt a jelly-roll beta-sandwich structure with a cleft into which amorphous cellulose and soluble cellooligosaccharides bind. To determine the orientation of the sugar chain within these binding clefts, the association of TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl-4-yl) spin-labeled derivatives of cellotriose and cellotetraose with isolated CBDN1 and CBDN2 was studied using heteronuclear 1H-15N NMR spectroscopy. Quantitative binding measurements indicate that the TEMPO moiety does not significantly perturb the affinity of the cellooligo-saccharide derivatives for the CBDs. The paramagnetic enhancements of the amide 1HN longitudinal (DeltaR1) and transverse (DeltaR2) relaxation rates were measured by comparing the effects of TEMPO-cellotetraose in its nitroxide (oxidized) and hydroxylamine (reduced) forms on the two CBDs. The bound spin-label affects most significantly the relaxation rates of amides located at both ends of the sugar-binding cleft of each CBD. Similar results are observed with TEMPO-cellotriose bound to CBDN1. This demonstrates that the TEMPO-labeled cellooligosaccharides, and by inference strands of amorphous cellulose, can associate with CBDN1 and CBDN2 in either orientation across their beta-sheet binding clefts. The ratio of the association constants for binding in each of these two orientations is estimated to be within a factor of five to tenfold. This finding is consistent with the approximate symmetry of the hydrogen-bonding groups on both the cellooligosaccharides and the residues forming the binding clefts of the CenC CBDs.

Binding Sites↗