Escherichia coli induces apoptosis and proliferation of mammary cells

Mammary cell apoptosis and proliferation were assessed after injection of Escherichia coli into the left mammary quarters of six cows. Bacteriological analysis of foremilk samples revealed coliform infection in the injected quarters of four cows. Milk somatic cell counts increased in these quarters and peaked at 24 h after bacterial injection. Body temperature also increased, peaking at 12 h postinjection, The number of apoptotic cells was significantly higher in the mastitic tissue than in the uninfected control. Expression of Bax and interleukin-1 beta converting enzyme increased in the mastitic tissue at 24 h and 72 h postinfection, whereas Bcl-2 expression decreased at 24 h but did not differ significantly from the control at 72 h postinfection, Induction of matrix metalloproteinase-g, stromelysin-1 and urokinase-type plasminogen activator was also observed in the mastitic tissue. Moreover, cell proliferation increased in the infected tissue, These results demonstrate that Escherichia coli-induced mastitis promotes apoptosis and cell proliferation

The Outcome of Phagocytic Cell Division with Infectious Cargo Depends on Single Phagosome Formation

Given that macrophages can proliferate and that certain microbes survive inside phagocytic cells, the question arises as to the post-mitotic distribution of microbial cargo. Using macrophage-like cells we evaluated the post-mitotic distribution of intracellular Cryptococcus yeasts and polystyrene beads by comparing experimental data to a stochastic model. For beads, the post-mitotic distribution was that expected from chance alone. However, for yeast cells the post-mitotic distribution was unequal, implying preferential sorting to one daughter cell. This mechanism for unequal distribution was phagosomal fusion, which effectively reduced the intracellular particle number. Hence, post-mitotic intracellular particle distribution is stochastic, unless microbial and/or host factors promote unequal distribution into daughter cells. In our system unequal cargo distribution appeared to benefit the microbe by promoting host cell exocytosis. Post-mitotic infectious cargo distribution is a new parameter to consider in the study of intracellular pathogens since it could potentially define the outcome of phagocytic-microbial interactions

Epithelial Tissues Have Varying Degrees of Susceptibility to KrasG12D-Initiated Tumorigenesis in a Mouse Model

Activating mutations in the Kras gene are commonly found in some but not all epithelial cancers. In order to understand the susceptibility of different epithelial tissues to Kras-induced tumorigenesis, we introduced one of the most common Kras mutations, KrasG12D, broadly in epithelial tissues. We used a mouse model in which the G12D mutation is placed in the endogenous Kras locus controlled by inducible, Cre-mediated recombination in tissues expressing cytokeratin 19 including the oral cavity, GI tract, lungs, and ducts of the liver, kidney, and the pancreas. Introduction of the KrasG12D mutation in adult mouse tissues led to neoplastic changes in some but not all of these tissues. Notably, many hyperplasias, metaplasias and adenomas were observed in the oral cavity, stomach, colon and lungs, suggesting that exposure to products of the outside environment promotes KrasG12D-initiated tumorigenesis. However, environmental exposure did not consistently correlate with tumor formation, such as in the small intestine, suggesting that there are also intrinsic differences in susceptibility to Kras activation. The pancreas developed small numbers of mucinous metaplasias with characteristics of early stage pancreatic intraepithelial neoplasms (PanINs), supporting the hypothesis that pancreatic ducts have the potential to give rise pancreatic cancer

Effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified: study protocol of a randomized controlled trial

Background: Disordered eating behavior and body dissatisfaction affect a large proportion of the Dutch population and account for severe psychological, physical and social morbidity. Yet, the threshold for seeking professional care is still high. In the Netherlands, only 7.5% of patients with bulimia nervosa and 33% of patients with anorexia nervosa are treated within the mental health care system. Easily accessible and low-threshold interventions, therefore, are needed urgently. The internet has great potential to offer such interventions. The aim of this study is to determine whether a web-based treatment program for patients with eating disorders can improve eating disorder psychopathology among female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified. Methods/design: This randomized controlled trial will compare the outcomes of an experimental treatment group to a waiting list control group. In the web-based treatment program, participants will communicate personally and asynchronously with their therapists exclusively via the internet. The first part of the program will focus on analyzing eating attitudes and behaviors. In the second part of the program participants will learn how to change their attitudes and behaviors. Participants assigned to the waiting list control group will receive no-reply email messages once every two weeks during the waiting period of 15 weeks, after which they can start the program. The primary outcome measure is an improvement in eating disorder psychopathology as determined by the Eating Disorder Examination Questionnaire. Secondary outcomes include improvements in body image, physical and mental health, body weight, self-esteem, quality of life, and social contacts. In addition, the participants’ motivation for treatment and their acceptability of the program and the therapeutic alliance will be measured. The study will follow the recommendations in the CONSORT statement relating to designing and reporting on RCTs. Discussion: This study protocol presents the design of a RCT for evaluating the effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified

Mammary Involution and Breast Cancer Risk: Transgenic Models and Clinical Studies

Postlactational involution is the process following weaning during which the mammary gland undergoes massive cell death and tissue remodeling as it returns to the pre-pregnant state. Lobular involution is the process by which the breast epithelial tissue is gradually lost with aging of the mammary gland. While postlactational involution and lobular involution are distinct processes, recent studies have indicated that both are related to breast cancer development. Experiments using a variety of rodent models, as well as observations in human populations, suggest that deregulation of postlactational involution may act to facilitate tumor formation. By contrast, new human studies show that completion of lobular involution protects against subsequent breast cancer incidence

Nutrition in children with CRF and on dialysis

The objectives of this study are: (1) to understand the importance of nutrition in normal growth; (2) to review the methods of assessing nutritional status; (3) to review the dietary requirements of normal children throughout childhood, including protein, energy, vitamins and minerals; (4) to review recommendations for the nutritional requirements of children with chronic renal failure (CRF) and on dialysis; (5) to review reports of spontaneous nutritional intake in children with CRF and on dialysis; (6) to review the epidemiology of nutritional disturbances in renal disease, including height, weight and body composition; (7) to review the pathological mechanisms underlying poor appetite, abnormal metabolic rate and endocrine disturbances in renal disease; (8) to review the evidence for the benefit of dietetic input, dietary supplementation, nasogastric and gastrostomy feeds and intradialytic nutrition; (9) to review the effect of dialysis adequacy on nutrition; (10) to review the effect of nutrition on outcome

Long-term outcome of chronic dialysis in children

As the prevalence of children on renal replacement therapy (RRT) increases world wide and such therapy comprises at least 2% of any national dialysis or transplant programme, it is essential that paediatric nephrologists are able to advise families on the possible outcome for their child on dialysis. Most children start dialysis with the expectation that successful renal transplantation is an achievable goal and will provide the best survival and quality of life. However, some will require long-term dialysis or may return intermittently to dialysis during the course of their chronic kidney disease (CKD). This article reviews the available outcome data for children on chronic dialysis as well as extrapolating data from the larger adult dialysis experience to inform our paediatric practice. The multiple factors that may influence outcome, and, particularly, those that can potentially be modified, are discussed

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events