Caseinomacropeptide specifically stimulates exocrine pancreatic secretion in the anesthetized rat

The effect of caseinomacropeptide (CMP) (the [106-169] fragment of kappa-casein produced during digestion of milk protein), was studied in anesthetized rats using bile diversion for a pure pancreatic juice collection system. Intraduodenal administration of CMP induced a dose-related specific stimulation of pancreatic secretion which was nearly abolished by devazepide, atropine, hexamethonium, vagotomy or perivagal capsaicin pretreatment. Moreover, CMP did not inhibit in vitro trypsin activity. These results demonstrate that CMP is more likely to stimulate pancreatic secretion specifically through cholecystokinin release and activation of a vago-vagal cholinergic reflex loop than by inhibition of luminal trypsin, in anesthetized rats.     

In vitro and in silico processes to identify differentially expressed proteins

We present an integrated proteomics platform designed for performing differential analyses. Since reproducible results are essential for comparative studies, we explain how we improved reproducibility at every step of our laboratory processes, e.g. by taking advantage of the powerful laboratory information management system we developed. The differential capacity of our platform is validated by detecting known markers in a real sample and by a spiking experiment. We introduce an innovative two-dimensional (2-D) plot for displaying identification results combined with chromatographic data. This 2-D plot is very convenient for detecting differential proteins. We also adapt standard multivariate statistical techniques to show that peptide identification scores can be used for reliable and sensitive differential studies. The interest of the protein separation approach we generally apply is justified by numerous statistics, complemented by a comparison with a simple shotgun analysis performed on a small volume sample. By introducing an automatic integration step after mass spectrometry data identification, we are able to search numerous databases systematically, including the human genome and expressed sequence tags. Finally, we explain how rigorous data processing can be combined with the work of human experts to set high quality standards, and hence obtain reliable (false positive < 0.35%) and nonredundant protein identifications.     

Development of the pancreas in medaka

In the present work, pancreatic organogenesis has been studied in the medaka (Oryzias latipes), a teleost fish with several advantages as an experimental system in developmental biology. We demonstrated that the pancreas develops from three primordia budding from the dorsal and ventral faces of the gut epithelium. Such buds then fuse to form a single endocrine islet surrounded by exocrine tissue. Interestingly, the endocrine tissue forms only from the dorsal bud. We next analyzed a collection of medakas that had been hybridized with cDNAs derived from an anterior brain library. We found new clones expressed in the pancreatic region demonstrating that the medaka can be used to define new genes expressed in the pancreatic region that follow a specific spatial and temporal pattern of expression.     

Age as a factor in breast cancer knowledge,attitudes and screening behaviour.

OBJECTIVE: To determine whether there are age-related differences in knowledge, attitudes and behaviour with respect to breast cancer and whether the differences reflect the age-specific Canadian recommendations on breast cancer screening. DESIGN: Telephone survey. SETTING: Two cities and five towns and their surrounding areas in Alberta. PARTICIPANTS: The age-specific, randomly selected sample comprised 1284 women aged 40 to 75 years who did not have breast cancer. Of the 1741 eligible women who were contacted, 1350 (78%) agreed to participate; 66 were excluded because of age ineligibility or a history of breast cancer. MAIN OUTCOME MEASURE: Frequency of knowledge, attitudes and behaviour with respect to breast cancer, by age group. RESULTS: Knowledge of breast cancer risk factors was generally low and decreased with age. Few women were aware of the Canadian recommendations on breast self-examination, physical examination of the breasts by a health care practitioner and mammographic screening. Older women believed they were less susceptible to breast cancer than younger women and were less likely to have positive attitudes toward screening. Self-examination was performed 9 to 15 times per year by 424 women (33%), and 810 (63%) had been examined by a health care professional in the past year. Although 664 (52%) had undergone mammography, the proportion decreased with age after age 59. The main barriers to mammography were lack of physician referral and the woman''s belief that the procedure is unnecessary if she is healthy. CONCLUSIONS: Education is needed to increase breast cancer knowledge, promote the Canadian recommendations for early detection of breast cancer and decrease negative beliefs about the disease. Changes in the behaviour of women and physicians are needed to increase the use of breast self-examination, clinical breast examination by a health care professional and mammographic screening. Reaching women in the upper range (60 to 69 years) of the target group for mammographic screening should be a focus in promoting early detection of breast cancer.     

Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26–3.23), age >70 years (OR 1.15, 95% CI 1.06–1.24), immobility (OR 2.06, 95% CI 1.93–2.19), renal insufficiency (OR 2.42, 95% CI 2.15–2.71) and anemia (OR 1.75, 95% CI 1.65–1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64–2.06), immobility (OR 1.51, 95% CI 1.30–1.76) and metastases (OR 3.22, 95% CI 2.87–3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision.     

Ribonucleotide Reductase Subunit M2 Predicts Survival in Subgroups of Patients with Non-Small Cell Lung Carcinoma: Effects of Gender and Smoking Status

BackgroundRibonucleotide reductase catalyzes the conversion of ribonucleotide diphosphates to deoxyribonucleotide diphosphates. The functional enzyme consists of two subunits - one large (RRM1) and one small (RRM2 or RRM2b) subunit. Expression levels of each subunit have been implicated in prognostic outcomes in several different types of cancers.ResultsIn non-small cell lung cancer (NSCLC), RRM2 expression was strongly predictive of disease-specific survival in women, non-smokers and former smokers who had quit at least 10 years prior to being diagnosed with lung cancer. Higher expression was associated with worse survival. This was not the case for men, current smokers and those who had stopped smoking for shorter periods of time. RRM1 was not predictive of survival outcomes in any subset of the patient group.ConclusionRRM2, but not RRM1, is a useful predictor of survival outcome in certain subsets of NSCLC patients.