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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

A nationwide family study of pulmonary embolism: Identification of high risk families with increased risk of hospitalized and fatal pulmonary embolism.

BACKGROUND: Family history is an important risk factor for deep venous thrombosis. However, few studies have determined the importance of family history of pulmonary embolism (PE). OBJECTIVE: This nationwide study aimed to determine the familial risks of fatal and hospitalized PE. METHODS: The Swedish Multi-Generation Register for subjects aged 0 to 76years old born since 1932 were linked to t

Neighborhood deprivation and mortality in individuals with cancer: a multilevel analysis from Sweden.

Little information is available on the effect of neighborhood deprivation on mortality in individuals with cancer. The aim of this study was to investigate the effect of level of neighborhood deprivation on mortality after a wide range of cancer diagnoses. This 1990-2004 follow-up study included all individuals in Sweden aged 25-74 years and used multilevel logistic regression with individual-leve

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

Occupational Risk Factors for Systemic Lupus Erythematosus: a Nationwide Study Based on Hospitalizations in Sweden.

OBJECTIVE: To investigate possible associations between occupation and hospitalization for systemic lupus erythematosus (SLE) in a nationwide study. METHODS: A nationwide database was constructed in Sweden by linking the Swedish Census to the Hospital Discharge Register to obtain data on all first hospitalizations with a primary or secondary diagnosis of SLE in adults during the study period (19

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

Intra-individual short-term variability of prostate-specific antigen and other kallikrein markers in a serial collection of blood from men under evaluation for prostate cancer.

Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b OBJECTIVES: To assess variation of total prostate-specific antigen (tPSA), free PSA (fPSA), percent fPSA, human glandular kallikrein 2 (hK2) and intact PSA measured three times within 2 weeks. Knowledge of the variation in an individual's PSA level is important for clinical decision-making. PATIENTS AND METHODS: Study participants w

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

Heritability and familiality of type 2 diabetes and related quantitative traits in the Botnia Study.

AIMS/HYPOTHESIS: To study the heritability and familiality of type 2 diabetes and related quantitative traits in families from the Botnia Study in Finland. METHODS: Heritability estimates for type 2 diabetes adjusted for sex, age and BMI are provided for different age groups of type 2 diabetes and for 34 clinical and metabolic traits in 5,810 individuals from 942 families using a variance compone

Neighbourhood socioeconomic status and coronary heart disease in individuals between 40 and 50 years.

OBJECTIVE: The incidence of myocardial infarction (MI) has decreased in general but not among younger middle-aged adults. We performed a cohort study of the association between neighbourhood socioeconomic status (SES) at the age of 40 and risk of MI before the age of 50 years. METHODS: All individuals in Sweden were included in the year of their 40th birthday, if it occurred between 1998 and 20

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

Population-based assessment of chronic myeloid leukemia in Sweden: striking increase in survival and prevalence.

The clinical outcome for patients with chronic myeloid leukemia (CML) has improved dramatically following the introduction of tyrosine kinase inhibitors. An improved survival, combined with a constant incidence, is expected to increase the prevalence of CML. However, data on the prevalence of CML remain scarce. We examined the overall and relative (age and gender matched) survival and assessed the

Angptl4 maintains in vivo repopulation capacity of CD34(+) human cord blood cells.

OBJECTIVES: Methods to expand hematopoietic stem cells (HSCs) ex vivo encompass an attractive approach that would substantially broaden the clinical applicability of HSCs derived from cord blood. Recently, members of the Angiopoietin-like (Angptl) family of growth factors were shown to expand both murine and human HSCs. Specifically, Angptl5 has been implicated in the expansion of human NOD-SCID-

Depression or anxiety and all-cause mortality in adults with atrial fibrillation - A cohort study in Swedish primary care.

Objective Our aim was to study depression and anxiety in atrial fibrillation (AF) patients as risk factors for all-cause mortality in a primary care setting. Methods The study population included adults (n = 12 283) of 45 years and older diagnosed with AF in 75 primary care centres in Sweden. The association between depression or anxiety and all-cause mortality was explored using Cox regression an

Family history and risk of hospital treatment for varicose veins in Sweden.

Abstract BACKGROUND: Family history has been suggested as a risk factor for varicose veins, but recall bias may inflate the familial risks. The aim of this nationwide study was to determine familial risks for hospital treatment for varicose veins. METHODS: Data from the Swedish Multi-Generation Register of people aged 0-76 years were linked to Hospital Discharge Register data for 1964-2008. Stand