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Long-term treatment with low-dose metoprolol CR/XL is associated with increased plaque echogenicity: The Beta-blocker Cholesterol-lowering Asymptomatic Plaque Study (BCAPS).

OBJECTIVES: To examine whether the decrease in IMT progression rate in the carotid bulb induced by metoprolol CR/XL treatment (25mg once daily) observed in the β-blocker Cholesterol-lowering Asymptomatic Plaque Study (BCAPS) was accompanied by an effect on carotid plaque echogenicity. METHODS: Gray scale median (GSM) in carotid plaques, used as a score of echogenicity, was measured at baseline and

Dietary Fat Intake and Development of Specific Breast Cancer Subtypes.

We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and satu

A New Look at Drugs Targeting Malignant Melanoma – An Application for Mass Spectrometry Imaging

Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors (PKI) has been highly effective for certain subsets of MM patients. Vemurafenib, a PKI targeting BR

Gene therapy cures the anemia and lethal bone marrow failure in mouse model for RPS19-deficient Diamond-Blackfan anemia.

Diamond-Blackfan anemia is a congenital erythroid hypoplasia caused by functional haploinsufficiency of genes encoding ribosomal proteins. Mutations involving the ribosomal protein S19 gene are detected in 25 % of patients. Enforced expression of ribosomal protein S19 improves the overall proliferative capacity, erythroid colony-forming potential and erythroid differentiation of hematopoietic prog

Characterization of Lewy body pathology in 12- and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease.

We previously reported the occurrence of Lewy bodies in grafted human fetal mesencephalic neurons in two patients with Parkinson's disease. Here, we have used immunohistochemistry and electron microscopy to characterize the development of Lewy bodies in one of these cases. This patient was operated in putamen on both sides at 12 or 16 years before death, respectively. We demonstrate that 2% of the

Genetic variants in serum and glucocortocoid regulated kinase 1, a regulator of the epithelial sodium channel, are associated with ischaemic stroke.

OBJECTIVE: Serum and glucocorticoid regulated kinase 1 (SGK1) expression is increased by aldosterone and is a key regulator of the amiloride-sensitive sodium channel (ENaC) in the distal nephron. We have previously shown that two SNPs in SGK1 (rs1057293 and rs1743966) are associated with blood pressure variation and blood pressure progression in the general population. Therefore, we tested the ass

Determining carotid plaque vulnerability using ultrasound center frequency shifts.

The leading cause of morbidity and mortality worldwide is atherosclerotic cardiovascular disease, most commonly caused by rupture of a high-risk plaque and subsequent thrombosis resulting in stroke, myocardial infarction or sudden death depending on the affected arterial territory. Accurate, non-invasive methods to identify such lesions known as vulnerable or high-risk plaques are currently sub-op

A scattering study of concentrated lens protein solutions and mixtures - Towards understanding the molecular origin of presbyopia

Popular Abstract in English The eye is a complex device in charge of producing clear and sharp images of the outside world. While some people need glasses early on in their lives, others have nearly perfect vision until, all of a sudden, they have to hold books or documents further and further away from their eyes to be able to read them and eventually have to resort to reading glasses. This visuaHealthy eye lenses are transparent and flexible, able to adapt shape in order to focus on far away and close-by objects. With age, however, this flexibility is lost, leading to a condition known as presbyopia. This vision disorder where close-by objects appear blurred commonly starts around the age of 40. The aim of this thesis is to elucidate the molecular origin of the gradual hardening of the c

New improved method for 2D arterial wall movement measurements

We have recently reported that the inner layers of the arteries, the intima-media complex, of common carotid artery, move as much in the longitudinal direction as in the radial direction, during the cardiac cycle. In order to study this phenomenon we have developed a high-resolution ultrasonic method that can simultaneously record both the longitudinal and the radial movements of the arterial wall

Genetic analysis of dasatinib-treated chronic myeloid leukemia rapidly developing into acute myeloid leukemia with monosomy 7 in Philadelphia-negative cells.

Despite the recent success of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), approximately 2-17% of patients develop clonal cytogenetic changes in the Philadelphia-negative (Ph(-)) cell population. A fraction of these patients, in particular those displaying trisomy 8 or monosomy 7, are at risk of developing a myelodysplastic syndrome (MDS) or acute myeloid l

Comparison of grey scale median (GSM) measurement in ultrasound images of human carotid plaques using two different softwares.

Grey scale median (GSM) measured on ultrasound images of carotid plaques has been used for several years now in research to find the vulnerable plaque. Centres have used different software and also different methods for GSM measurement. This has resulted in a wide range of GSM values and cut-off values for the detection of the vulnerable plaque. The aim of this study was to compare the values obta

Galiellalactone is a Direct Inhibitor of STAT3 in Prostate Cancer Cells.

The transcription factor STAT3 is constitutively active in several malignancies including castration-resistant prostate cancer and has been identified as a promising therapeutic target. The fungal metabolite galiellalactone, a STAT3 signaling inhibitor, inhibits the growth, both in vitro and in vivo, of prostate cancer cells expressing active STAT3 and induces apoptosis of prostate cancer stem cel

Radiolabeled antibodies in prostate cancer: A case study showing the effect of host immunity on antibody bio-distribution.

Human tumors xenografted in immunodeficient mice are crucial models in nuclear medicine to evaluate the effectiveness of candidate diagnostic and therapeutic compounds. However, little attention has been focused on the biological profile of the host model and its potential effects on the bio-distribution and tumor targeting of the tracer compound under study. We specifically investigated the dissi

Identification of a Novel Proteoform of Prostate Specific Antigen (SNP-L132I) in Clinical Samples by Multiple Reaction Monitoring.

Prostate specific antigen (PSA) is a well-established tumor marker, which is frequently employed as model biomarker to develop and evaluate emerging quantitative proteomics techniques, partially due to wide access to commercialized immunoassays serving as "gold standard". We designed a multiple reaction monitoring (MRM) assay to detect PSA proteoforms in clinical samples (n=72), utilizing specific

miR-34c is down regulated in prostate cancer and exerts tumor suppressive functions.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. There have been several reports of miRNA deregulation in prostate cancer and the biological evidence for an involvement of miRNAs in prostate tumorigenesis is increasing. In this study, we show that miR-34c is downregulated in prostate cancer (p = 0.0005) by performing qRT-PCR on 49 TURPs from prosta