T-cell receptor Vbeta gene usage in CSF lymphocytes in X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder with impaired very-long-chain fatty acid (VLCFA) metabolism that produces a neurological disease with significant variability of clinical phenotypes even within kindred. The two most common forms are the cerebral form (CALD) with an important inflammatory reaction at the active edge of demyelinating lesions, resembling some aspects of multiple sclerosis pathology, and adrenomyeloneuropathy (AMN), which involves the spinal cord and in which the inflammatory reaction is mild or absent. One hypothesis is that the phenotypic variability is related to T cell-mediated immune mechanisms playing a primary role in the demyelinating pathogenic process of CALD.

Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans.

The melanocortin-4 receptor (MC4R), a centrally expressed G protein-coupled receptor (GPCR), is essential for the maintenance of long-term energy balance in humans. Mutations in MC4R are the most common genetic cause of obesity. Since activation of this receptor leads to a decrease in food intake, MC4R is also a major therapeutic target for the treatment of obesity.

Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity.

Elucidating the signalling mechanisms by which obesity leads to impaired insulin action is critical in the development of therapeutic strategies for the treatment of diabetes. Recently, mice deficient for S6 Kinase 1 (S6K1), an effector of the mammalian target of rapamycin (mTOR) that acts to integrate nutrient and insulin signals, were shown to be hypoinsulinaemic, glucose intolerant and have reduced beta-cell mass. However, S6K1-deficient mice maintain normal glucose levels during fasting, suggesting hypersensitivity to insulin, raising the question of their metabolic fate as a function of age and diet.

Use of tuf sequences for genus-specific PCR detection and phylogenetic analysis of 28 streptococcal species.

A 761-bp portion of the tuf gene (encoding the elongation factor Tu) from 28 clinically relevant streptococcal species was obtained by sequencing amplicons generated using broad-range PCR primers. These tuf sequences were used to select Streptococcus-specific PCR primers and to perform phylogenetic analysis. The specificity of the PCR assay was verified using 102 different bacterial species, including the 28 streptococcal species.

Elicited repetitive daily blindness: a new familial disorder related to migraine and epilepsy.

The authors report a family affected by multiple daily episodes of transient visual loss, elicited repetitive daily blindness (ERDB); the onset was early in life, and the disease followed a benign course. ERDB is associated with childhood epilepsy and familial hemiplegic migraine, apparently segregating as a monogenic, autosomal dominant condition with variable expression. Genetic linkage to CACNA1A was excluded.

Laboratory detection of group B Streptococcus for prevention of perinatal disease.

Group B Streptococcus (GBS) or Streptococcus agalactiae emerged in the 1970s as the leading cause of neonatal morbidity and mortality. Today, GBS remains one of the leading causes of sepsis and meningitis in newborns despite important prevention efforts, including the issuance of recommendations for prevention of perinatal GBS disease by the American College of Obstetricians and Gynecologists, the Centers for Disease Control and Prevention, and the American Academy of Pediatrics in 1996/1997. The gastrointestinal tract is the natural human reservoir for GBS and is the likely source of vaginal colonization.

Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma.

Calorie restriction extends lifespan in organisms ranging from yeast to mammals. In yeast, the SIR2 gene mediates the life-extending effects of calorie restriction. Here we show that the mammalian SIR2 orthologue, Sirt1 (sirtuin 1), activates a critical component of calorie restriction in mammals; that is, fat mobilization in white adipocytes.

New real-time PCR assay for rapid detection of methicillin-resistant Staphylococcus aureus directly from specimens containing a mixture of staphylococci.

Molecular methods for the rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) are generally based on the detection of an S. aureus-specific gene target and the mecA gene. However, such methods cannot be applied for the direct detection of MRSA from nonsterile specimens such as nasal samples without the previous isolation, capture, or enrichment of MRSA because these samples often contain both coagulase-negative staphylococci (CoNS) and S.

[Epilepsy and genetics].

Our knowledge in the field of epilepsy has evolved since the discovery of new specific inherited epilepsy syndromes. Causal mutations have been identified for some of these syndromes. They involve various ionic channels: Na+ channels in the generalized epilepsy with febrile seizures plus (GEFS+) among the idiopathic generalized epilepsies, nicotinic receptors in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), K+ channels in benign familial neonatal convulsions, and GABAA receptors in some forms of generalized epilepsy.

Development of a protocol for the isolation of Listeria monocytogenes from sludge.

Given the high level of background flora in sludge, methods for detecting Listeria monocytogenes are not well established. In this study, two critical parameters for the detection of L. monocytogenes were evaluated: the concentration of Listeria sp.

"Tumor-mimicking" multiple sclerosis.

The spectrum of clinical manifestations of multiple sclerosis (MS) may include rare cases where cerebral lesions simulate brain tumors or abscesses on neuroimaging. We report here on a 43-year-old woman with numerous ring-enhancing cystic lesions in the white matter of cerebral hemispheres, brainstem and cerebellum. The radiological picture was overwhelmingly in favor of a metastatic or infectious etiology, but brain biopsy showed subacute demyelination with central necrosis.

Real-time PCR assay for detection of fluoroquinolone resistance associated with grlA mutations in Staphylococcus aureus.

Resistance to fluoroquinolones among clinical isolates of Staphylococcus aureus has become a clinical problem. Therefore, a rapid method to identify S. aureus and its susceptibility to fluoroquinolones could provide clinicians with a useful tool for the appropriate use of these antimicrobial agents in the health care settings.

The estrogen antagonist EM-652 and dehydroepiandrosterone prevent diet- and ovariectomy-induced obesity.

Objective: EM-652 is a pure antiestrogen in human breast and uterine cancer cells that also reduces bone loss and plasma lipid levels in the rat. This study aimed to assess the ability of EM-652, alone or with dehydroepiandrosterone (DHEA), to prevent obesity and related metabolic abnormalities induced by an obesity-promoting diet and ovariectomy.

Research Methods And Procedures: Female rats were fed a high-sucrose, high-fat (HSHF) diet, were left intact or ovariectomized (OVX), and were treated with EM-652, DHEA, or both for 20 days.

Exploration of a putative susceptibility locus for idiopathic generalized epilepsy on chromosome 8p12.

Purpose: A recent genome-wide scan revealed a major susceptibility locus for idiopathic generalized epilepsies (IGEs) in the chromosomal region 8p12 in 32 IGE families without members with juvenile myoclonic epilepsy (JME). This study explored the presence of an IGE locus in the chromosomal region 8p12.

Methods: Our study included 176 multiplex families of probands with common IGE syndromes.

Rapid detection of Clostridium difficile in feces by real-time PCR.

Clostridium difficile is the major causative agent of nosocomial antibiotic-associated diarrhea, colitis, and pseudomembranous colitis. The pathogenicity of C. difficile is closely related to the production of toxins A and B.

Rapid molecular theranostics in infectious diseases.

The increasing availability of rapid and sensitive nucleic acid testing assays for infectious diseases will revolutionize the practice of medicine by gradually reducing the need for standard culture-based microbiological methods that take at least two days. Molecular theranostics in infectious diseases is an emerging concept in which molecular biology tools are used to provide rapid and accurate diagnostic assays to enable better initial management of patients and more efficient use of antimicrobials. Essential conditions and the quality control required for the development and validation of such molecular theranostic assays are reviewed.

Nuclear receptors and the control of metabolism.

The metabolic nuclear receptors act as metabolic and toxicological sensors, enabling the organism to quickly adapt to environmental changes by inducing the appropriate metabolic genes and pathways. Ligands for these metabolic receptors are compounds from dietary origin, intermediates in metabolic pathways, drugs, or other environmental factors that, unlike classical nuclear receptor ligands, are present in high concentrations. Metabolic receptors are master regulators integrating the homeostatic control of (a) energy and glucose metabolism through peroxisome proliferator-activated receptor gamma (PPARgamma); (b) fatty acid, triglyceride, and lipoprotein metabolism via PPARalpha, beta/delta, and gamma; (c) reverse cholesterol transport and cholesterol absorption through the liver X receptors (LXRs) and liver receptor homolog-1 (LRH-1); (d) bile acid metabolism through the farnesol X receptor (FXR), LXRs, LRH-1; and (e) the defense against xeno- and endobiotics by the pregnane X receptor/steroid and xenobiotic receptor (PXR/SXR).

SRC-1 and TIF2 control energy balance between white and brown adipose tissues.

We have explored the effects of two members of the p160 coregulator family on energy homeostasis. TIF2-/- mice are protected against obesity and display enhanced adaptive thermogenesis, whereas SRC-1-/- mice are prone to obesity due to reduced energy expenditure. In white adipose tissue, lack of TIF2 decreases PPARgamma activity and reduces fat accumulation, whereas in brown adipose tissue it facilitates the interaction between SRC-1 and PGC-1alpha, which induces PGC-1alpha's thermogenic activity.

Detection of enteroviral RNA (poliovirus types 1 and 3) in endomyocardial biopsies from patients with ventricular tachycardia and survivors of sudden cardiac death.

The purpose of this study was to determine the prevalence of enteroviral infection in the myocardium of consecutive patients with serious ventricular arrhythmias by using a reverse transcription nested PCR followed by direct DNA sequencing. After exclusion of coronary heart disease, right ventricular endomyocardial biopsies were obtained from 32 consecutive patients with a history of ventricular tachycardia or sudden cardiac death. Control biopsies were obtained from 36 subjects with no history of viral myocarditis, dilated cardiomyopathy, ventricular tachycardia or recent infection.

N-substituted 4-(4-carboxyphenoxy)benzamides. Synthesis and evaluation as inhibitors of steroid-5alpha-reductase type 1 and 2.

In search of non-steroidal inhibitors of human prostatic 5alpha-reductase, we recently described N-substituted 4'-biphenyl-4-carboxylic acids. Here, we report the optimisation of this series of compounds by increasing the conformational flexibility using an ether linker between the steroidal A-C ring mimetics. Ten new compounds were synthesised and tested against human and rat isozymes 1 and 2.

Progesterone receptor knockout mice have an improved glucose homeostasis secondary to beta -cell proliferation.

Gestational diabetes coincides with elevated circulating progesterone levels. We show that progesterone accelerates the progression of diabetes in female dbdb mice. In contrast, RU486, an antagonist of the progesterone receptor (PR), reduces blood glucose levels in both female WT and dbdb mice.

Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia.

A map of 191 single-nucleotide polymorphism (SNPs) was built across a 5-Mb segment from chromosome 13q34 that has been genetically linked to schizophrenia. DNA from 213 schizophrenic patients and 241 normal individuals from Canada were genotyped with this marker set. Two 1,400- and 65-kb regions contained markers associated with the disease.