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A hypothesis-generating search for new genetic breast cancer syndromes - a national study in 803 Swedish families

Among Swedish families with an inherited predisposition for breast cancer, less than one third segregate mutations in genes known to be associated with an increased risk of breast cancer in combination with other types of tumours. In a search for new putative familial breast cancer syndromes we studied Swedish families undergoing genetic counselling during 1992-2000. Four thousand families from co

Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFP/ALK5 signaling

Transforming growth factor-beta (TGFbeta) regulates the activation state of the endothelium via two opposing type I receptor/Smad pathways. Activin receptor-like kinase-1 (ALK1) induces Smad1/5 phosphorylation, leading to an increase in endothelial cell proliferation and migration, while ALK5 promotes Smad2/3 activation and inhibits both processes. Here, we report that ALK5 is important for TGFbet

Brain damage and hypoxia in an ovine fetal chronic cocaine model

OBJECTIVE: To assess the development of brain damage in an ovine fetal chronic cocaine model. To evaluate the effect of isolated hypoxic tests on this model and to correlate hemodynamic findings (brain-sparing effect) following fetal hypoxia and the occurrence of brain damage. STUDY DESIGN: Fifteen ewes were divided into a control group (n=7) and a cocaine treated group (n=8). From day 65 to day 1

Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Alcohol consumption may be associated with risk of colorectal cancer (CRC), but the epidemiological evidence for an association with specific anatomical subsites, types of alcoholic beverages and current vs. lifetime alcohol intake is inconsistent. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 478,732 study subjects free of cancer at enrolment between 1992 and 200

Broome and the Intuition of Neutrality

In “Weighing Lives” (2004) John Broome criticizes a view common to many population axiologists. This is the view that population increases with extra people leading decent lives are axiologically neutral: they make the world neither better nor worse, ceteris paribus. Broome argues that this intuition, however, attractive, cannot be sustained, for several independent reasons. I respond to his criti

CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth

This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts overexpressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. Mechanistic st

Fluorescence spectroscopy in tissue phantoms for improved depth resolution in tissue imaging

A way to determine the depth of an embedded fluorescent object, for example deep-lying tumors marked with a fluorescent probe, is to detect fluorescent light that has propagated through the medium at two different wavelength bands. A ratio can then be calculated between the corresponding intensities. The wavelength regions should be chosen such that there is a difference in the absorption in the m

Neuroarchitecture of the central complex of the desert locust: Intrinsic and columnar neurons

The central complex is a group of neuropils in the center of the insect brain. It consists of four major subunits: the upper and lower divisions of the central body (CBU, CBL), the protocerebral bridge (PB), and the paired noduli. A distinctive feature of the central complex is a modular architecture characterized by rows of 16 columns, intersected in the central body by stacks of layers. Evidence

Endometrial expression of the estrogen-sensitive genes MMP-26 and TIMP-4 is altered by a substitution protocol without down-regulation in IVF patients.

BACKGROUND: The aim of this study was to analyse the effects of an estradiol (E2)–progesterone substitution protocol on the endometrial expression of estrogen-sensitive genes during the peri-implantation period. METHODS: Peripheral blood and endometrial biopsies were obtained from 13 infertile women both in a natural cycle (NC), on days 5 and 7 after ovulation (NC5, NC7), and in an artificial (sub

Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16

Objective. To study the clinical recovery from acute otitis media ( AOM) in children, 2-16 years of age, managed with or without treatment with phenoxymethylpenicillin ( PcV). Design. An open, prospective randomized trial. Children aged between 2 and 16 years, presenting with one- or double-sided AOM ( without perforation) with symptom duration of less than four days, were included. The children w

Von Willebrand factor/factor VIII concentrate (Haemate(R) P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery.

Background: While plasma-derived concentrates containing large amounts of von Willebrand factor (VWF) are effective in treating von Willebrand disease (VWD), optimal dosing remains to be fully characterized. Objectives: To determine the feasibility of dosing Haemate P-(R) VWF/factor VIII (FVIII) concentrate based on pharmacokinetics (PK) in the management of surgical subjects with VWD. Methods: VW

Displacement of the occluding loop by the parasite protein, chagasin, results in efficient inhibition of human cathepsin

Cathepsin B is a papain-like cysteine protease showing both endo- and exopeptidase activity, the latter due to a unique occluding loop that restricts access to the active site cleft. To clarify the mode by which natural protein inhibitors manage to overcome this obstacle, we have analyzed the structure and function of cathepsin B in complexes with the Trypanosoma cruzi inhibitor, chagasin. Kinetic

Bral1, a brain-specific link protein, colocalizing with the versican V2 isoform at the nodes of Ranvier in developing and adult, mouse central nervous systems

Bral1, a brain-specific hyaluronan-binding protein, has been cloned recently. To gain insight into the role of Bral1, we generated a specific antibody against this protein. We have examined the detailed localization pattern of Bral1 protein and compared it with that of other members of the lectican proteoglycan family, such as brevican and versican, with which Bral1 is predicted to interact. The i

Semmelweis’s methodology from the modern stand-point: intervention studies and causal ontology

Semmelweis’s work predates the discovery of the power of randomization in medicine by almost a century. Although Semmelweis would not have consciously used a randomized controlled trial (RCT), some features of his material—the allocation of patients to the first and second clinics—did involve what was in fact a randomization, though this was not realised at the time. This article begins by explain

Pyruvate decarboxylases from the petite-negative yeast Saccharomyces kluyveri

Saccharomyces kluyveri is a petite-negative yeast, which is less prone to form ethanol under aerobic conditions than is S. cerevisiae. The first reaction on the route from pyruvate to ethanol is catalysed by pyruvate decarboxylase, and the differences observed between S. kluyveri and S. cerevisiae with respect to ethanol formation under aerobic conditions could be caused by differences in the regu

Cross-Cultural Patterns in College Student Drinking and its Consequences - A Comparison between the USA and Sweden

Aims: The aim of the study was to compare alcohol use, consequences and common risk factors between American and Swedish college students. Methods: A secondary comparative analysis from one American and two Swedish studies in college settings. Results: Swedish freshmen report higher alcohol use than US freshmen students. Swedish residence hall students report higher alcohol use than US residence h

Type 1 fimbriae deliver an LPS- and TLR4-dependent activation signal to CD14-negative cells

Fimbriae target bacteria to different mucosal surfaces and enhance the inflammatory response at these sites. Inflammation may be triggered by the fimbriae themselves or by fimbriae-dependent delivery of other host activating molecules such as lipopolysaccharide (LPS). Although LPS activates systemic inflammation through the CD14 and Toll-like receptor 4 (TLR4) pathways, mechanisms of epithelial ce

Links between worlds: unraveling migratory connectivity

Migration is the regular seasonal movement of animals from one place to another, often from a breeding site to a nonbreeding site and back. Because the act of migration makes it difficult to follow individuals and populations year round, our understanding of the ecology and evolution of migrating organisms, particularly binds, has been severely impeded. Exciting new advances in satellite telemetry