Preparation of β-Hydroxyketones (Aldols) from the Alkylation of -Silyl Aryl Cyanohydrins with Epoxides.

β-Hydroxyketones (aldols) are prepared from the alkylation-deprotection of -silylated aryl cyanohydrins with epoxides. Key to the success of the method was the suppression of an cyclic imidate formation that occurs upon initial opening of the epoxide ring.

Factors that influence adherence and strategies to maintain adherence to injected therapies for patients with multiple sclerosis.

A key aspect of the management of care for patients with multiple sclerosis (MS) is identifying which patients are struggling with adherence. Disease-modifying therapies for the treatment of MS are primarily preventative, with modest efficacy, and they can possibly cause significant side effects. These factors can lead patients to stop taking their medication because they continue to experience symptoms or relapses of the disease, and/or they have painful injection-site reactions on most parts of their bodies.

Injectable disease-modifying therapy for relapsing-remitting multiple sclerosis: a review of adherence data.

Long-term adherence to disease-modifying therapy in relapsing-remitting multiple sclerosis (RRMS) is associated with improved patient outcomes, including a reduced risk of relapse and a better preserved quality of life. However, the unpredictable nature of the disease--even when it is being treated--may make it difficult to convince patients of the importance of treatment adherence. A number of studies have attempted to pinpoint factors that affect adherence.

Emerging multiple sclerosis oral therapies.

Currently, patients suffering from multiple sclerosis (MS), a chronic demyelinating disorder of the CNS, must be injected with medication to provide modest relief for their symptoms. Five orally available therapies are being evaluated in phase II/III clinical trials. If these therapies prove safe and tolerable, oral compounds may improve patient endorsement and compliance.

Multiple sclerosis immunology: The healthy immune system vs the MS immune system.

Multiple sclerosis (MS) is a debilitating autoimmune disease characterized by both inflammation and axonal degeneration. The resulting demyelination and subsequent degeneration of axons account for the disability of patients with MS. Early investigations indicated that disease progression was driven by CD4(+) effector T cells.

Molecular profiling of matched samples identifies biomarkers of papillary thyroid carcinoma lymph node metastasis.

Biomarkers of papillary thyroid carcinoma (PTC) metastasis can accurately identify metastatic cells and aggressive tumor behavior. To find new markers, serial analysis of gene expression (SAGE) was done on three samples from the same patient: normal thyroid tissue, primary PTC, and a PTC lymph node metastasis. This genomewide expression analysis identified 31 genes expressed in lymph node metastasis, but not in the primary tumor.

The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, paralysis and death within 2-5 years of diagnosis. Currently, no effective pharmacological agents exist for the treatment of this devastating disease. Neuroinflammation may accelerate the progression of ALS.

Diagnosis of suspicious thyroid nodules using four protein biomarkers.

Purpose: Fine-needle aspiration (FNA) cytology, a standard method for thyroid nodule diagnosis, cannot distinguish between benign follicular thyroid adenoma (FTA) and malignant follicular thyroid carcinoma (FTC). Previously, using expression profiling, we found that a combination of transcript expression levels from DDIT3, ARG2, C1orf24, and ITM1 distinguished between FTA and FTC. The goal of this study was to determine if antibody markers used alone or in combination could accurately distinguish between a wider variety of benign and malignant thyroid lesions in fixed sections and FNA samples.

Statistical challenges with gene expression studies.

Studies that include high-throughput data, such as gene expression data, raise unique issues with respect to study design and analysis. At the same time, they should be viewed through the lens (albeit a modified one) of standard scientific approach that involves such issues as specifying objectives (even if the study is mainly hypothesis generating or exploratory), a careful consideration of design, including sample size and replication, deciding whether to include technical replication in addition to biological replication, and ensuring that the methods of analysis are appropriate for the objective.

NAD(P)H oxidase contributes to the progression of remote hepatic parenchymal injury and endothelial dysfunction, but not microvascular perfusion deficits.

Oxidative stress occurs in remote liver injury, but the origin of the oxidant generation has yet to be thoroughly delineated. Some reports suggest that the source of the distant oxidative stress originates from the site of initial insult [i.e.

Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors.

This study examined the ability of the endocannabinoids 2-arachidonoyl glycerol (2-AG) and noladin ether as well as the synthetic cannabinoid CP-55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol] to regulate three intracellular effectors via CB2 receptors in transfected Chinese hamster ovary cells. Although the three agonists regulate all effectors with equivalent efficacy, the rank order of potencies differs depending on which effector is evaluated. Noladin ether and CP-55,940 most potently inhibit adenylyl cyclase, requiring higher concentrations to stimulate the extracellular signal-regulated kinase subgroup of the mitogen-activated protein kinases (extracellular signal-regulated kinase-mitogen-activated protein kinase; ERK-MAPK) and Ca(2+)-transients.

The endocannabinoid noladin ether acts as a full agonist at human CB2 cannabinoid receptors.

Noladin ether (NE) is a putative endogenously occurring cannabinoid demonstrating agonist activity at CB1 receptors. Because of reported selective affinity for CB1 receptors, the pharmacological actions of NE at CB2 receptors have not been examined. Therefore, the purpose of this study was to characterize the binding and functional properties of NE at human CB2 receptors stably expressed in Chinese hamster ovary (CHO) cells as well as in HL-60 cells, which express CB2 receptors endogenously.

MedlineR: an open source library in R for Medline literature data mining.

Summary: We describe an open source library written in the R programming language for Medline literature data mining. This MedlineR library includes programs to query Medline through the NCBI PubMed database; to construct the co-occurrence matrix; and to visualize the network topology of query terms. The open source nature of this library allows users to extend it freely in the statistical programming language of R.

A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression.

Accurate diagnosis of thyroid tumors is challenging. A particular problem is distinguishing between follicular thyroid carcinoma (FTC) and benign follicular thyroid adenoma (FTA), where histology of fine-needle aspirates is not conclusive. It is often necessary to remove healthy thyroid to rule out carcinoma.

An anatomy of normal and malignant gene expression.

A gene's expression pattern provides clues to its role in normal physiology and disease. To provide quantitative expression levels on a genome-wide scale, the Cancer Genome Anatomy Project (CGAP) uses serial analysis of gene expression (SAGE). Over 5 million transcript tags from more than 100 human cell types have been assembled.

Statistical issues with microarrays: processing and analysis.

The study of gene expression with printed arrays and prefabricated chips is evolving from a qualitative to a quantitative science. Statistical procedures for determining quality control, differential expression, and reproducibility of findings are a natural consequence of this evolution. However, problems inherent to the technologies have raised important issues of how to apply adequate statistical tests.