Histamine induces the expression of uncoupling protein 2 (UCP2) and acid-binding protein (aP2) in white adipocytes.

Background: The aim of the present study was to investigate whether histamine induces up-regulated expression of uncoupling protein 2 (UCP2) and fat acid-binding protein (aP2) in white adipocytes (differentiated 3T3-L1 cells).

Methods: Differentiation of 3T3-L1 preadipocytes to adipocytes was induced by the addition of 5 microg/mL insulin, 1 micromol/L dexamethasone, 10 mmol/L 1-isobutyl-3-methylxanthine, 1% dimethylsulfoxide, and 10% fetal bovine serum in Dulbecco's modification of Eagle's medium. Total RNA from differentiated 3T3-L1 cells was extracted and semi-quantitative RT-PCR was performed to determine the levels of UCP2 and aP2 mRNA.

The genetic polymorphisms of beta3-adrenergic receptor (AR) Trp64Arg and beta2-AR Gln27Glu are associated with obesity in Chinese male hypertensive patients.

Background: Genetic polymorphisms of beta3-adrenergic receptor (AR) Trp64Arg and beta2-AR Gln27Glu may result in significant change in the functions of these receptors. The aims of the present study were to investigate the association between Trp64Arg, Arg16Gly and Gln27Glu polymorphisms and the susceptibility to obesity and hypertension in a Chinese population.

Methods: A total of 437 Chinese subjects including 149 obese hypertensive patients, 139 non-obese essential hypertensive patients, and 149 non-obese normotensive healthy controls were enrolled in the study.

Fetal central nervous system anomalies: comparison of magnetic resonance imaging and ultrasonography for diagnosis.

Background: Evaluation of fetal central nervous system (CNS) agenesis by ultrasonography (US) is frequently limited, but magnetic resonance imaging (MRI) has its own advantages and is gaining popularity in displaying suspected fetal anomalies. The purpose of this study was to explore the value of MRI in detecting fetal CNS agenesis.

Methods: Thirty-four women (aged from 22 to 35 years, average 27 years) with complicated pregnancies (16 - 39 weeks of gestation, average 30 weeks) were examined with a 1.

Pharmacogenetics of SLCO1B1 gene and the impact of *1b and *15 haplotypes on irinotecan disposition in Asian cancer patients.

Objective: To investigate the pharmacogenetic effect of SLCO1B1 *1a, *1b, *5 and *15 polymorphisms on irinotecan disposition in Asian cancer patients.

Experimental Design: Irinotecan was administered over 90 min either at 100 mg/m on days 1, 8 and 15 with the regimen being repeated every 28 days (N=28) or at 375 mg/m once every three weeks (N=43). Plasma concentrations of irinotecan, 7-ethyl-10-hydroxycamptothecin and 7-ethyl-10-hydroxycamptothecinG were analysed after the first dose of the first cycle and the influence of SLCO1B1 *1a, *1b, *5 and *15 polymorphisms on the disposition of irinotecan and its metabolites were evaluated.

Comparative effects of paclitaxel and rapamycin on smooth muscle migration and survival: role of AKT-dependent signaling.

Objective: Advances in stent technology have enabled the delivery of drugs to improve outcomes after stent deployment. However, the optimal payloads for stents are not clear, and the appropriate stent-based therapies for high-risk patients, such as diabetics, have not been clearly established.

Methods And Results: We used smooth muscle cell culture models to compare the activities of rapamycin and paclitaxel.

Overexpression of RB1 transcript is significantly correlated with 13q14 allelic imbalance in colorectal carcinomas.

RB1 gene expression has been reported to be upregulated in colorectal carcinomas (CRC) at both the mRNA and protein levels when compared to normal colonic mucosa. However, allelic loss at the genomic level has been detected in CRC with widely differing frequencies ranging from 11.5% to 50%.

Regulation of the cytoplasmic quality control protein degradation pathway by BAG2.

The cytoplasm is protected against the perils of protein misfolding by two mechanisms: molecular chaperones (which facilitate proper folding) and the ubiquitin-proteasome system, which regulates degradation of misfolded proteins. CHIP (carboxyl terminus of Hsp70-interacting protein) is an Hsp70-associated ubiquitin ligase that participates in this process by ubiquitylating misfolded proteins associated with cytoplasmic chaperones. Mechanisms that regulate the activity of CHIP are, at present, poorly understood.

[Haplotype and linkage analysis in Chinese hereditary mixed polyposis syndrome].

Objective: To investigate if hereditary mixed polyposis syndrome (HMPS) locus of two Singapore Chinese HMPS families is identical with the Ashkenazi families.

Methods: Genomic DNA was extracted, multiplex polymerase chain reaction (PCR) was used to amplify 4 microsatellite markers D15S1010, D15S1007, ACTC and D15S118 in 31 individuals from two families. The HMPS locus cosecretion of the markers on 15q13 over a region of 2.

Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I.

Muscle-specific RING finger protein 1 (MuRF1) is a sarcomere-associated protein that is restricted to cardiac and skeletal muscle. In skeletal muscle, MuRF1 is up-regulated by conditions that provoke atrophy, but its function in the heart is not known. The presence of a RING finger in MuRF1 raises the possibility that it is a component of the ubiquitin-proteasome system of protein degradation.

Muscle ring finger protein-1 inhibits PKC{epsilon} activation and prevents cardiomyocyte hypertrophy.

Much effort has focused on characterizing the signal transduction cascades that are associated with cardiac hypertrophy. In spite of this, we still know little about the mechanisms that inhibit hypertrophic growth. We define a novel anti-hypertrophic signaling pathway regulated by muscle ring finger protein-1 (MURF1) that inhibits the agonist-stimulated PKC-mediated signaling response in neonatal rat ventricular myocytes.

Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy by participating in an SCF ubiquitin ligase complex.

Calcineurin, which binds to the Z-disc in cardiomyocytes via alpha-actinin, promotes cardiac hypertrophy in response to numerous pathologic stimuli. However, the endogenous mechanisms regulating calcineurin activity in cardiac muscle are not well understood. We demonstrate that a muscle-specific F-box protein called atrogin-1, or muscle atrophy F-box, directly interacts with calcineurin A and alpha-actinin-2 at the Z-disc of cardiomyocytes.

NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.

The Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder characterized by facial dysmorphia, upper-extremity malformations, hirsutism, cardiac defects, growth and cognitive retardation, and gastrointestinal abnormalities. Both missense and protein-truncating mutations in NIPBL, the human homolog of the Drosophila melanogaster Nipped-B gene, have recently been reported to cause CdLS. The function of NIPBL in mammals is unknown.

Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.

Cornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited multisystem developmental disorder characterized by growth and cognitive retardation; abnormalities of the upper limbs; gastroesophageal dysfunction; cardiac, ophthalmologic and genitourinary anomalies; hirsutism; and characteristic facial features. Genital anomalies, pyloric stenosis, congenital diaphragmatic hernias, cardiac septal defects, hearing loss and autistic and self-injurious tendencies also frequently occur. Prevalence is estimated to be as high as 1 in 10,000 (ref.

CHIP activates HSF1 and confers protection against apoptosis and cellular stress.

Induction of molecular chaperones is the characteristic protective response to environmental stress, and is regulated by a transcriptional program that depends on heat shock factor 1 (HSF1), which is normally under negative regulatory control by molecular chaperones Hsp70 and Hsp90. In metazoan species, the chaperone system also provides protection against apoptosis. We demonstrate that the dual function co-chaperone/ubiquitin ligase CHIP (C-terminus of Hsp70-interacting protein) regulates activation of the stress-chaperone response through induced trimerization and transcriptional activation of HSF1, and is required for protection against stress-induced apoptosis in murine fibroblasts.

ApoA-I structure on discs and spheres. Variable helix registry and conformational states.

Apolipoprotein A-I (apoA-I) readily forms discoidal high density lipoprotein (HDL) particles with phospholipids serving as an ideal transporter of plasma cholesterol. In the lipid-bound conformation, apoA-I activates the enzyme lecithin:cholesterol acyltransferase stimulating the formation of cholesterol esters from free cholesterol. As esterification proceeds cholesterol esters accumulate within the hydrophobic core of the discoidal phospholipid bilayer transforming it into a spherical HDL particle.

Better anticoagulation control improves survival after valve replacement.

Objective: We sought to assess the effect of anticoagulation control on long-term survival after valve replacement with the Medtronic Hall valve (Medtronic, Inc, Minneapolis, Minn).

Methods: Prospective follow-up data, including 82,297 international normalized ratios, were collected for 1476 patients undergoing single valve replacement with the Medtronic Hall valve between 1979 and 1994, with follow-up to the end of 1998. After excluding 204 patients who either died within 30 days or had fewer than 10 international normalized ratios recorded beyond 30 days, there were 10,203 patient years of follow-up for analysis.