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Reduced repression of cytokine signaling ameliorates age-induced decline in hematopoietic stem cell function.

Aging causes profound effects on the hematopoietic stem cell (HSC) pool, including an altered output of mature progeny and enhanced self-propagation of repopulating-defective HSCs. An important outstanding question is whether HSCs can be protected from aging. The signal adaptor protein LNK negatively regulates hematopoiesis at several cellular stages. It has remained unclear how the enhanced sensi

Cripto Regulates Hematopoietic Stem Cells as a Hypoxic-Niche-Related Factor through Cell Surface Receptor GRP78.

Hematopoietic stem cells (HSCs) are maintained in hypoxic niches in endosteal regions of bones. Here we demonstrate that Cripto and its receptor GRP78 are important regulators of HSCs in the niche. Flow cytometry analyses revealed two distinct subpopulations of CD34(-)KSL cells based on the expression of GRP78, and these populations showed different reconstitution potential in transplantation assa

Flow cytometry-based identification of immature myeloerythroid development.

Precursor cells of the myeloerythroid cell lineages give rise to mature cells of the granulocyte, monocyte, erythroid, and/or thrombocytic lineages. High-resolution profiling of the developmental stages, from hematopoietic stem cells to mature progeny, is important to study and understand the underlying mechanisms that guide various cell fate decisions. In addition, this approach provides greater

Cotinine validation of self-reported smoking during pregnancy in the Swedish Medical Birth Register.

Self-reported data on smoking during pregnancy from the Medical Birth Register of Sweden (MBR) are widely used. However, underreporting of such behaviour may occur, leading to biases. It is of importance to validate the smoking data in the MBR. The main objective was to investigate the agreement between self-reported smoking data from the MBR and cotinine levels in maternal serum among women from

A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). One potential therapeutic strategy for MS is to induce regulatory cells that mediate immunological tolerance. Probiotics, including lactobacilli, are known to induce immunomodulatory activity with promising effects in inflammatory diseases. We tested the potential of various strain

Genetic loci for bone architecture determined by three-dimensional CT in crosses with the diabetic GK rat.

The F344 rat carries alleles contributing to bone fragility while the GK rat spontaneously develops type-2 diabetes. These characteristics make F344xGK crosses well suited for the identification of genes related to bone size and allow for future investigation on the association with type-2 diabetes. The aim of this study was to identify quantitative trait loci (QTLs) for bone size phenotypes measu

Determination of 14 Circulating microRNAs in Swedes and Iraqis with and without Diabetes Mellitus Type 2.

Recent reports suggest that immigrants from Middle Eastern countries are a high-risk group for type 2 diabetes (T2D) compared with Swedes, and that the pathogenesis of T2D may be ethnicity-specific. Deregulation of microRNA (miRNA) expression has been demonstrated to be associated with T2D but ethnic differences in miRNA have not been investigated. The aim of this study was to explore the ethnic s

Gene-Lifestyle Interactions in Complex Diseases: Design and Description of the GLACIER and VIKING Studies.

Most complex diseases have well-established genetic and non-genetic risk factors. In some instances, these risk factors are likely to interact, whereby their joint effects convey a level of risk that is either significantly more or less than the sum of these risks. Characterizing these gene-environment interactions may help elucidate the biology of complex diseases, as well as to guide strategies

Ethnic Differences in Incidence of Type 1 Diabetes among Second-Generation Immigrants and Adoptees from Abroad.

Objective: The incidence of type 1 diabetes shows a large variation worldwide, but whether the causes are environmental or genetic has not been settled. We examine here the incidence of type 1 diabetes among second-generation immigrants and adoptees from abroad to disentangle genetic/ethnic vs. environmental influence, assuming adoptees from abroad have similar environmental exposures compared wit

Long-term course of Mycobacterium tuberculosis infection in Swedish birth cohorts during the twentieth century.

Abstract SETTING: Sweden under transition from high to low tuberculosis (TB) incidence from 1920 to 2009. OBJECTIVE: To correlate estimates of TB infection in birth cohorts with the longitudinal incidence of active TB to assess the long-term risk and time pattern of reactivated TB. DESIGN: Time trend analysis on TB incidence using age-cohort modelling. RESULTS: The overall TB incidence decrease

High salt intake increases copeptin but salt sensitivity is associated with fluid induced reduction of copeptin in women.

This study investigated if copeptin is affected by high salt intake and whether any salt-induced changes in copeptin are related to the degree of salt sensitivity. The study was performed on 20 men and 19 women. In addition to meals containing 50 mmol NaCl daily, capsules containing 100 mmol NaCl and corresponding placebo capsules were administered during 4 weeks each, in random order. Measurement

Country of birth and risk of hospitalization due to heart failure: a Swedish population-based cohort study.

To explore the relation between country of birth and risk of hospitalization due to heart failure (HF). All 40-89 year-old inhabitants in the city of Malmö, Sweden (n = 114,917, of whom 15.2% were born outside Sweden) were followed from November 1st, 1990 until December 31st, 2007. During a mean follow-up of 13.5 ± 5.3 years, a total of 7,640 individuals (47.4% men) were discharged from hospital w

Case-report: EBV driven lymphoproliferative disorder associated with Ruxolitinib.

Ruxolitinib, a novel inhibitor of Janus kinases 1 and 2, was recently approved for the treatment of myelofibrosis but, recently, attention has been drawn to potential side effects and especially opportunistic infections and virus reactivations. EBV reactivation has not previously been reported to occur in association with Ruxolitinib.

Knee cartilage quality assessed with dGEMRIC in rheumatoid arthritis patients before and after treatment with a TNF inhibitor.

BACKGROUND: TNF-α inhibitors are potent anti-inflammatory drugs that have revolutionized the treatment of rheumatoid arthritis (RA). Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a non-invasive method to study cartilage quality, in particular the glycosaminoglycan (GAG) content. PURPOSE: To evaluate knee cartilage quality before and after treatment with a TNF-α inhibitor (infliximab) i

Association of central and peripheral pulse pressure with intermediate cardiovascular phenoytpes.

OBJECTIVE: We assessed the relationship between pulse pressure and intermediate cardiovascular phenotypes in a middle-aged cohort with high prevalence of hypertension. BACKGROUND: It has been suggested that central pulse pressure (cPP) is a better predictor of cardiovascular outcome than peripheral pulse pressure (pPP), particularly in the elderly. Yet, it is unclear if cPP provides additional pro

Trends in out-of-hospital ischaemic heart disease deaths 1992 to 2003 in southern Sweden.

AIMS: In western countries out-of-hospital ischaemic heart disease (IHD) deaths account for approximately 50-70% of all IHD deaths. The objective was to examine the trends in out-of-hospital IHD deaths in the Region of Skåne in southern Sweden, in different sex- and age-groups. METHODS: All 14,347 persons (range 24-110 years) in Skåne who died out-of-hospital between 1992 and 2003 from IHD (I410-

A Clinical Scoring Algorithm for Determination of the Risk of Tuberculosis in HIV-Infected Adults: A Cohort Study Performed at Ethiopian Health Centers.

The World Health Organization (WHO) tuberculosis (TB) symptom screening instrument (WHO-TB) can identify human immunodeficiency virus (HIV)-infected individuals at low risk of tuberculosis (TB); however, many patients report WHO-TB symptoms and require further TB investigations. We hypothesized that further clinical scoring could classify subjects with a positive WHO-TB screening result (WHO-TB(+)

TARGETING NEUROINFLAMMATION FOR TREATMENT OF ISCHEMIC STROKE.

Ischemic stroke is a major cause of adult disability. Stroke-induced brain damage is accompanied by inflammation - activation of resident microglia and infiltration of blood-circulating monocytes. The effect of these cells on neuro-plasticity and recovery after stroke could be detrimental as well as beneficial. The future challenge is to understand the mechanisms of action of immune cells on cellu