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Targeting p53 in Vivo: A First-in-Human Study With p53-Targeting Compound APR-246 in Refractory Hematologic Malignancies and Prostate Cancer.

PURPOSEAPR-246 (PRIMA-1MET) is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. The main aims of this first-in-human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of APR-246. PATIENTS AND METHODSAPR-246 was administered as a 2-hour intravenous infusion once per day for 4 consecutive d

Sex differences in risk factor control of treated hypertensives: a national primary healthcare-based study in Sweden.

BACKGROUND: To evaluate potential sex differences, this study aimed to investigate blood pressure and lipid control and other risk factors for cardiovascular disease in treated hypertensive (tHT) patients from primary healthcare. DESIGN AND METHODS: This cross-sectional survey of tHT patients was carried out between 2002 and 2005 by 264 primary care physicians from Sweden who consecutively recruit

Beyond the brain: widespread pathology in Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a polyglutamine stretch in the huntingtin protein. Today, more than 15 years after the genetic defect underlying HD was discovered, the pathogenesis is still not well understood and there is no adequate treatment. Research into this disorder has conventionally focused on neurological symptoms and brain pathology, partic

Droplet-target laser-plasma source for proximity x-ray lithography

A compact, high-brightness and practically debris-free laser-plasma soft x-ray source for proximity x-ray lithography is described. The target of the source is small liquid fluorocarbon droplets injected into vacuum with a piezoelectrically vibrated nozzle. Emission from helium- and hydrogenlike fluorine in the 1.2-1.7 nm wavelength range was determined to similar to 2X10(12) photons/(sr-pulse). w

Purification and Functional Characterization of C4b-Binding Protein (C4BP).

C4b-binding protein (C4BP) is a soluble, 570 kDa large glycoprotein, present in plasma at a concentration of approximately 200 mg/L. C4BP is the main inhibitor of the classical and lectin pathways of complement, where it controls C4b-mediated reactions. Here, we describe a method for purification of C4BP from human plasma, which is based on barium chloride precipitation, anion exchange chromatogra

Emigration flows from North Africa to Europe.

The region of North Africa (NA) represents a striking locality regarding migration with several migration patterns, namely emigration in the form of labour export to Europe and North America and, to a lesser extent, to the Arab Gulf area. The latter has increased enormously in the last decade because of the political instability in most of the NA countries. The aim of the present chapter was to ex

Taloside Inhibitors of Galectin-1 and Galectin-3

Galectin-1 and galectin-3 have roles in cancer and inflammation. Galectin-1 has recently emerged as a significant protein produced by tumour cells to promote tumour development, angiogenesis and metastasis and consequently represents an important target to inhibit. The design of inhibitors targeting the carbohydrate recognition domain that is known to recognize galactose is an important approach i

Probing impulsive strain propagation with x-ray pulses

Pump-probe time-resolved x-ray diffraction of allowed and nearly forbidden reflections in InSb is used to follow the propagation of a coherent acoustic pulse generated by ultrafast laser excitation. The surface and bulk components of the strain could be simultaneously measured due to the large x-ray penetration depth. Comparison of the experimental data with dynamical diffraction simulations sugge

Circulatory recovery is as fast with air ventilation as with 100% oxygen after asphyxia-induced cardiac arrest in piglets.

We investigated return of spontaneous circulation and of cerebral oxygenation after asphyxia-induced cardiac arrest, using ventilation with air, throughout, or with 100% oxygen for a shorter or longer period. Arterial pressure, heart rate, regional cerebral oxygen saturation (CrSO2) and brain tissue oxygen tension (PbtO2) were measured in one day old piglets that were hypoventilated with air and l

Circulating maternal cortisol levels during vaginal delivery and elective cesarean section.

Maternal S-cortisol levels increase throughout pregnancy and peak in the third trimester. Even higher levels are seen during the physical stress of delivery. Since analgesia for women in labor has improved, it is possible that maternal stress during labor is reduced. The aim of this study was to compare maternal S-cortisol during vaginal delivery and elective cesarean section.

The idic(X)(q13) in myeloid malignancies: breakpoint clustering in segmental duplications and association with TET2 mutations.

Myelodysplastic syndromes and acute myeloid leukemia with an isodicentric X chromosome [idic(X)(q13)] occur in elderly women and frequently display ringed sideroblasts. Because of the rarity of idic(X)(q13), little is known about its formation, whether a fusion gene is generated, and patterns of additional aberrations. We here present a SNP array study of 14 idic(X)-positive myeloid malignancies,

A mathematical model for predicting the temperature distribution in laser-induced hyperthermia. Experimental evaluation and applications

A time-dependent mathematical model for the heat transfer in laser-induced hyperthermia has been developed. The model calculates the temperature distribution in surface-irradiated tissues. Good agreement was found between the predictions of the model and in vitro experimental results obtained for bovine liver irradiated with an expanded beam from a Nd:YAG laser. Surface evaporation of water was in

The expression of pluripotency marker Oct 3/4 in prostate cancer and benign prostate hyperplasia.

BACKGROUND: Oct 3/4 (Octamer 3/4), a member of POU family has been considered as an important stem cell marker and essential transcription factor during human embryogenesis. In recent years, there have also been reports on presence of Oct 3/4 in differentiated benign and malignant human cells. The objective of this study was to investigate the transcription and the protein expression of Oct 3/4 is

Clinical application of long-term intensity and pitch matches in fluctuating low-frequency hearing loss.

The purpose of this study was to measure changes in intensity and pitch matches to better assess disease activity in fluctuating hearing loss. Long-term suprathreshold audiometry was carried out at home on a subject with a unilateral fluctuating low-frequency hearing loss during a period when the subject demonstrated no symptoms and a period when the subject reported hearing loss, aural pressure,

Serum transferrin carrying the xeno-tetrasaccharide NeuAc-Gal-GlcNAc2 is a biomarker of ALG1-CDG.

ALG1-CDG (formerly CDG-Ik) is a subtype of congenital disorders of glycosylation (CDG) where the genetic defect disrupts the synthesis of the lipid-linked oligosaccharide precursor required for N-glycosylation. The initial step in the investigation for these disorders involves the demonstration of hypoglycosylated serum transferrin (TF). There are no specific biomarkers of this CDG subtype known t