Clear cell renal carcinoma presenting as a bleeding cyst in pregnancy: inaugural manifestation of a von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is a dominant autosomal disorder inducing the development of many tumors, such as hemangioblastomas in the central nervous system and retina, cysts or tumors (benign or malignant) in the kidneys and/or the pancreas. We report the case of a pregnant woman who presented with a voluminous hemorrhagic cyst of the right kidney with an exophytic lesion detected in the lower median part of the cyst wall. As an anamnestic inquiry resulted in a familial history of VHL disease, a screening imaging was performed and detected three medullary hemangioblastomas.

SARS vaccine based on a replication-defective recombinant vesicular stomatitis virus is more potent than one based on a replication-competent vector.

A SARS vaccine based on a live-attenuated vesicular stomatitis virus (VSV) recombinant expressing the SARS-CoV S protein provides long-term protection of immunized mice from SARS-CoV infection (Kapadia, S.U., Rose, J.

Adult subjects with Prader-Willi syndrome show more low-grade systemic inflammation than matched obese subjects.

Aim: Adult subjects with Prader-Willi syndrome (PWS) may show several conditions that are associated with an activation of innate immunity such as obesity, deficient GH secretion or hypogonadism. Our aim was to study whether obese adult PWS subjects show an additional low-grade systemic inflammation (LGSI) in relation to obese adult non-PWS subjects and lean healthy control subjects before and after a standardized liquid meal.

Methods: Seven obese adult PWS subjects, 7 matched obese non-PWS subjects and 7 lean healthy control subjects were studied for 6 h from the administration of a standard liquid meal.

Insulin sensitivity and resistin levels in gestational diabetes mellitus and after parturition.

Context: Resistin is expressed and secreted by the placenta during pregnancy. Increased serum resistin levels have been found in the second half of normal pregnancy, but its role in the pathogenesis of the insulin resistance of pregnancy is undetermined.

Objective: The objective of the study was to assess the relationship between circulating resistin levels and insulin sensitivity in gestational diabetes mellitus (GDM).

Genome-wide transcriptional analysis of the human cell cycle identifies genes differentially regulated in normal and cancer cells.

Characterization of the transcriptional regulatory network of the normal cell cycle is essential for understanding the perturbations that lead to cancer. However, the complete set of cycling genes in primary cells has not yet been identified. Here, we report the results of genome-wide expression profiling experiments on synchronized primary human foreskin fibroblasts across the cell cycle.

Twins discordant for fetal skeletal abnormalities: a natural confrontation between the two siblings.

Background: Skeletal abnormalities encompass a heterogeneous group of disorders characterized by anomalies of cartilage as well as bone growth and development. Some are lethal and express early during fetal life, making them amenable to prenatal diagnosis. The increasing use of routine ultrasonography (US) during pregnancy permits a reliable primary evaluation of the fetal skeleton.

A multiparametric panel for ovarian cancer diagnosis, prognosis, and response to chemotherapy.

Purpose: Our goal was to examine a panel of 11 biochemical variables, measured in cytosolic extracts of ovarian tissues (normal, benign, and malignant) by quantitative ELISAs for their ability to diagnose, prognose, and predict response to chemotherapy of ovarian cancer patients.

Experimental Design: Eleven proteins were measured (9 kallikreins, B7-H4, and CA125) in cytosolic extracts of 259 ovarian tumor tissues, 50 tissues from benign conditions, 35 normal tissues, and 44 tissues from nonovarian tumors that metastasized to the ovary. Odds ratios and hazard ratios and their 95% confidence interval were calculated.

Probing the two-metal ion mechanism in the restriction endonuclease BamHI.

The choreography of restriction endonuclease catalysis is a long-standing paradigm in molecular biology. Bivalent metal ions are required almost for all PD..

Molecular characteristics of liver metastases from uveal melanoma.

Purpose: The liver is the most common site of systemic metastases from uveal melanoma (UM). Such metastases usually continue to develop despite the application of current treatment modalities. This study was conducted to obtain insight into the molecular pathways that underlie the development of UM metastasis and thus to identify potential novel therapeutic pathways for this disease.

Impact of ligand protonation on virtual screening against beta-secretase (BACE1).

Structure-based virtual screens were carried out against beta-secretase (BACE1) to investigate the impact of ligand protonation on screening efficacy. A comparative evaluation of the performance and its dependence on ligand protonation states docking by Surflex, eHiTS, GOLD, and FlexX-Pharm was performed. Virtual screening performed by FlexX-Pharm (EF(1%)=69) and Surflex (EF(1%)=58) provided the best efficiency.

TOPDB: topology data bank of transmembrane proteins.

The Topology Data Bank of Transmembrane Proteins (TOPDB) is the most complete and comprehensive collection of transmembrane protein datasets containing experimentally derived topology information currently available. It contains information gathered from the literature and from public databases available on the internet for more than a thousand transmembrane proteins. TOPDB collects details of various experiments that were carried out to learn about the topology of particular transmembrane proteins.

Molecular principles of the interactions of disordered proteins.

Thorough knowledge of the molecular principles of protein-protein recognition is essential to our understanding of protein function at the cellular level. Whereas interactions of ordered proteins have been analyzed in great detail, complexes of intrinsically unstructured/disordered proteins (IUPs) have hardly been addressed so far. Here, we have collected a database of 39 complexes of experimentally verified IUPs, and compared their interfaces with those of 72 complexes of ordered, globular proteins.

Combined analysis reveals a core set of cycling genes.

Background: Global transcript levels throughout the cell cycle have been characterized using microarrays in several species. Early analysis of these experiments focused on individual species. More recently, a number of studies have concluded that a surprisingly small number of genes conserved in two or more species are periodically transcribed in these species.

Continuous hidden process model for time series expression experiments.

Motivation: When analyzing expression experiments, researchers are often interested in identifying the set of biological processes that are up- or down-regulated under the experimental condition studied. Current approaches, including clustering expression profiles and averaging the expression profiles of genes known to participate in specific processes, fail to provide an accurate estimate of the activity levels of many biological processes.

Results: We introduce a probabilistic continuous hidden process Model (CHPM) for time series expression data.

Tamoxifen induces heparanase expression in estrogen receptor-positive breast cancer.

Purpose: Mammalian heparanase degrades heparan sulfate, the main polysaccharide of the basement membrane. Heparanase is an important determinant in cancer progression, acting via the breakdown of extracellular barriers for invasion, as well as release of heparan sulfate-bound angiogenic and growth-promoting factors. The present study was undertaken to elucidate molecular mechanisms responsible for heparanase overexpression in breast cancer.

Lower heart rate variability is associated with higher plasma concentrations of IL-6 in type 1 diabetes.

Objective: In type 1 diabetes, cardiovascular autonomic neuropathy (CAN) is associated with cardiovascular risk factors related to insulin resistance, which in turn are associated with low-grade systemic inflammation. Reduced heart rate variability (HRV) is considered one of the first indicators of CAN. Since the autonomic nervous system interacts with systemic inflammation, we evaluated CAN to study its possible association with low-grade systemic inflammation.

Spanish methodological approach for biosphere assessment of radioactive waste disposal.

The development of radioactive waste disposal facilities requires implementation of measures that will afford protection of human health and the environment over a specific temporal frame that depends on the characteristics of the wastes. The repository design is based on a multi-barrier system: (i) the near-field or engineered barrier, (ii) far-field or geological barrier and (iii) the biosphere system. Here, the focus is on the analysis of this last system, the biosphere.

B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125 expression.

Objective: This study characterizes the expression of the novel biomarker B7-H4 in ovarian cancer tissue, normal ovaries, and benign ovarian tumors, and evaluates its relationship to CA125.

Methods: Ovarian tissue lysates from 251 patients with ovarian carcinoma were assessed for the levels of B7-H4 and CA125 by ELISA assays. For comparison, ovarian tissues from patients with benign ovarian tumors (n=43) and patients with normal ovaries (n=32) were tested.

Electrostatic versus nonelectrostatic effects in DNA sequence discrimination by divalent ions Mg2+ and Mn2+.

Mg2+ and Mn2+ ions are critical to the functioning of phosphoryl transfer enzymes, such as restriction endonucleases. Although these ions play similar roles in the chemical steps, they govern substrate specificity via modulating sequence discrimination by up to a factor of 10(5) with Mg2+ and only up to a factor of 10 with Mn2+. To explain whether such diversity originates in fundamental differences in the electronic structures of the nucleobase-hydrated-metal ion complexes, structures and interaction energies were determined at the density functional (DFT) and second-order Møller-Plesset (MP2) levels of theory.

Evaluation of the novel serum markers B7-H4, Spondin 2, and DcR3 for diagnosis and early detection of ovarian cancer.

Objective: Early detection through regular screening could significantly reduce mortality from ovarian cancer. Advances in biomarkers and imaging continue to improve the sensitivity and specificity of cancer detection, but further improvements are still needed. In this study, we identified and evaluated three new serum biomarkers that may be used to improve detection of ovarian cancer.

An EcoRI-RsrI chimeric restriction endonuclease retains parental sequence specificity.

To test their structural and functional similarity, hybrids were constructed between EcoRI and RsrI, two restriction endonucleases recognizing the same DNA sequence and sharing 50% amino acid sequence identity. One of the chimeric proteins (EERE), in which the EcoRI segment His147-Ala206 was replaced with the corresponding RsrI segment, showed EcoRI/RsrI-specific endonuclease activity. EERE purified from inclusion bodies was found to have approximately 100-fold weaker activity but higher specific DNA binding affinity, than EcoRI.

[Evaluation of a multifaceted intervention for implementing national guidelines: the case of physical restraint in geriatric care].

Background: There is a growing interest in developing guidelines. The French Agency for accreditation and Evaluation (Anaes) published in October 2000 guidelines on the use of restraint in geriatric care settings because in spite of the risks this practice remains widespread in that type of care setting. A multifaceted intervention was conducted in a Parisian geriatric hospital in order to improve the implementation of the published guidelines.

Prediction of protein disorder at the domain level.

Intrinsically disordered/unstructured proteins exist in a highly flexible conformational state largely devoid of secondary structural elements and tertiary contacts. Despite their lack of a well defined structure, these proteins often fulfill essential regulatory functions. The intrinsic lack of structure confers functional advantages on these proteins, allowing them to adopt multiple conformations and to bind to different binding partners.

Local structural disorder imparts plasticity on linear motifs.

Motivation: The dynamic nature of protein interaction networks requires fast and transient molecular switches. The underlying recognition motifs (linear motifs, LMs) are usually short and evolutionarily variable segments, which in several cases, such as phosphorylation sites or SH3-binding regions, fall into locally disordered regions. We probed the generality of this phenomenon by predicting the intrinsic disorder of all LM-containing proteins enlisted in the Eukaryotic Linear Motif (ELM) database.