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Shaping up a lineage-lessons from B lymphopoesis.

Even though the development of B lymphoid cells from hematopoietic stem cells is one of the most carefully investigated models of cell differentiation in adult mammalians, a set of recent findings has to a large extent increased our understanding for how B lymphoid commitment is achieved. These include the identification of IKAROS, PU.1 and E2A as transcription factors responsible for lymphoid lin

Hematopoietic stem cells are regulated by Cripto, as an intermediary of HIF-1α in the hypoxic bone marrow niche.

Cripto has been known as an embryonic stem (ES)- or tumor-related soluble/cell membrane protein. In this study, we demonstrated that Cripto has a role as an important regulatory factor for hematopoietic stem cells (HSCs). Recombinant Cripto sustained the reconstitution ability of HSCs in vitro. Flow cytometry analysis uncovered that GRP78, one of the candidate receptors for Cripto, was expressed o

Normative Calcaneal Quantitative Ultrasound Data as an Estimation of Skeletal Development in Swedish Children and Adolescents.

We present age- and gender-specific normative bone status data evaluated by quantitative ultrasound (QUS) in the calcaneus with the Lunar Achilles device and compare these estimates with bone mineral content (BMC) and bone mineral density (BMD) estimated by dual X-ray absorptiometry (DXA). Included were a sample of 518 population-based collected Swedish girls and 558 boys aged 6-19 years. QUS meas

Comminuted fractures of the radial head.

BACKGROUND: There have been few reports on the long-term outcome of comminuted radial head fractures in adults. METHOD: 10 women and 9 men with a mean age of 45 (21-65) years when they sustained a comminuted fracture of the radial head were re-evaluated after 15-25 years. 6 patients had been nonoperatively (NO) treated while 13 had had a radial head excision. The uninjured elbow served as a contro

Prevalence and incidence of rheumatoid arthritis in southern Sweden 2008 and their relation to prescribed biologics.

Objectives. To gain updated estimates of prevalence and incidence of RA and proportion on biological treatment in southern Sweden. Methods. Inpatient and outpatient health care provided to residents in the southernmost county of Sweden (1.2 million inhabitants) is registered in the Skåne Health Care Register (SHCR). We identified residents aged >/=20 years who had received a diagnosis of RA at lea

Altered matrix production in the distal airways of individuals with asthma.

BACKGROUND AND AIMS: Although increasing evidence suggests involvement of the distal airway in all stages of asthma, it is not known whether structural changes (defined as airway remodelling) occur in the distal airways of subjects with mild asthma and those with atopy. The aim of this study was to compare control subjects and those with mild asthma in relation to fibroblast phenotypes and remodel

Road traffic noise, air pollution and myocardial infarction: a prospective cohort study.

Both road traffic noise and air pollution have been linked to cardiovascular disease. However, there are few prospective epidemiological studies available where both road traffic noise and air pollution have been analyzed simultaneously. The aim of this study was to investigate the relation between road traffic noise, air pollution and incident myocardial infarction in both current (1-year average

Fixed ratio or lower limit of normal as cut-off value for FEV1/VC: An outcome study.

There is no consensus on the appropriate cut-off level for the ratio between forced expiratory volume and vital capacity (FEV1/VC) for the diagnosis of chronic obstructive pulmonary disease (COPD). Application of a fixed ratio of 0.7 carries the risk of false positive diagnoses in elderly subjects and false negative diagnoses in younger subjects. The use of the lower limit of normal (LLN) of an in

High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event.

Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia.

Blood biomarkers and measures of pulmonary function-A study from the Swedish twin registry.

OBJECTIVE: There is great need of biomarkers for research and clinical purposes in COPD. This study explored the relationships between ten putative plasma biomarkers of COPD and physiological measures of reduced lung function. METHODS: FEV(1), FVC, residual volume/total lung capacity (RV/TLC) and CO diffusion capacity (D(L)CO) were assessed in 357 subjects from the Swedish Twin Registry. The l

Success Story of Targeted Therapy in Chronic Myeloid Leukemia: A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2008.

PURPOSE Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. PATIENTS AND METHODS Using data from the population-based Swedish Can

Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular β-glucosidases.

The membrane lipid glucosylceramide (GlcCer) is continuously formed and degraded. Cells express two GlcCer-degrading β-glucosidases, GBA and GBA2, located in and outside the lysosome, respectively. Here we demonstrate that through transglucosylation both GBA and GBA2 are able to catalyze in vitro the transfer of glucosyl-moieties from GlcCer to cholesterol, and vice versa. Furthermore, the natural

Lung function, forced expiratory volume in 1 s decline and COPD hospitalisations over 44 years of follow-up.

The use of baseline lung function in the prediction of chronic obstructive pulmonary disease (COPD) hospitalisations, all-cause mortality and lung function decline was assessed in the population-based "Men Born in 1914" cohort.Spirometry was assessed at age 55 years in 689 subjects, of whom 392 had spirometry reassessed at age 68 years. The cohort was divided into three groups using fixed ratio (F

P-selectin mediates neutrophil rolling and recruitment in acute pancreatitis.

BACKGROUND: The adhesive mechanisms regulating leucocyte-endothelium interactions in the pancreas remain elusive, but selectins may play a role. This study examined the molecular mechanisms mediating leucocyte rolling along the endothelium in the pancreas and the therapeutic potential of targeting the rolling adhesive interaction in acute pancreatitis (AP). METHODS: Pancreatitis was induced by ret

Enterolactone and breast cancer: methodological issues may contribute to conflicting results in observational studies.

Lignans found in plant foods are converted by the intestinal microflora to enterolignans. The structure of enterolignans is similar to that of estrogens, which has inspired researchers to examine a potential protective association in relation to health outcomes. Numerous epidemiological studies have measured concentration of enterolignans, mainly enterolactone, in blood or urine as a biomarker of

Toward Brain Tumor Gene Therapy Using Multipotent Mesenchymal Stromal Cell Vectors.

Gene therapy of solid cancers has been severely restricted by the limited distribution of vectors within tumors. However, cellular vectors have emerged as an effective migratory system for gene delivery to invasive cancers. Implanted and injected multipotent mesenchymal stromal cells (MSCs) have shown tropism for several types of primary tumors and metastases. This capacity of MSCs forms the basis

A high eating frequency is associated with an overall healthy lifestyle in middle-aged men and women and reduced likelihood of general and central obesity in men.

The role of eating frequency in obesity development is debated. Therefore, we investigated the association between eating frequency, BMI and waist circumference (WC), as well as how eating frequency is related to diet composition and lifestyle factors. A subsample (aged 47-68 years) of men (n 1355) and women (n 1654) from the Malmö Diet and Cancer cohort was used for the present cross-sectional st

RNAi screen identifies MAPK14 as a druggable suppressor of human hematopoietic stem cell expansion.

We report on a forward RNAi screen in primary human hematopoietic stem and progenitor cells, using pooled lentiviral shRNA libraries deconvoluted by next generation sequencing. We identify MAPK14/p38α as a modulator of ex vivo stem cell proliferation and show that pharmacological inhibition of p38 dramatically enhances the stem cell activity of cultured umbilical cord blood derived hematopoietic c