Solution structure of a bovine immunodeficiency virus Tat-TAR peptide-RNA complex.

The Tat protein of bovine immunodeficiency virus (BIV) binds to its target RNA, TAR, and activates transcription. A 14-amino acid arginine-rich peptide corresponding to the RNA-binding domain of BIV Tat binds specifically to BIV TAR, and biochemical and in vivo experiments have identified the amino acids and nucleotides required for binding. The solution structure of the RNA-peptide complex has now been determined by nuclear magnetic resonance spectroscopy.

Agouti structure and function: characterization of a potent alpha-melanocyte stimulating hormone receptor antagonist.

The murine agouti gene encodes for a novel 131 amino acid protein. The sequence includes a 22 residue putative secretion signal, an internal basic region, and a C-terminal domain containing 10 cysteines. Agouti has been found to antagonize the binding of certain pro-opiomelanocortin peptides, such as alpha-melanocyte stimulating hormone (alpha-MSH), to the murine melanocortin-1 receptor (MC1-R).

A YAC contig and an EST map in the pericentromeric region of chromosome 13 surrounding the loci for neurosensory nonsyndromic deafness (DFNB1 and DFNA3) and limb-girdle muscular dystrophy type 2C (LGMD2C).

Two forms of inherited childhood nonsyndromic deafness (DFNB1 and DFNA3) and a Duchenne-like form of progressive muscular dystrophy (LGMD2C) have been mapped to the pericentromeric region of chromosome 13. To clone the genes responsible for these diseases we constructed a yeast artificial chromosome (YAC) contig spanning an 8-cM region between the polymorphic markers D13S175 and D13S221. The contig comprises 24 sequence-tagged sites, among which 15 were newly obtained.

Agouti antagonism of melanocortin binding and action in the B16F10 murine melanoma cell line.

Several dominant mutations at the murine agouti locus result in the expression of a number of phenotypic changes, including a predominantly yellow coat color, obesity, and hyperinsulinemia. The mutants exhibit ectopic overexpression of normal agouti protein, suggesting that agouti regulates coat coloration by direct antagonism of the alpha-melanocyte-stimulating hormone receptor. We have tested this hypothesis by examining agouti inhibition of both melanocortin-stimulated cyclic adenosine monophosphate production and the binding of a radioactive melanocortin analog in the murine B16F10 melanoma cell line.

Defective myosin VIIA gene responsible for Usher syndrome type 1B.

Usher syndrome represents the association of a hearing impairment with retinitis pigmentosa and is the most frequent cause of deaf-blindness in humans. It is inherited as an autosomal recessive trait which is clinically and genetically heterogeneous. Some patients show abnormal organization of microtubules in the axoneme of their photoreceptors cells (connecting cilium), nasal ciliar cells and sperm cells, as well as widespread degeneration of the organ of Corti.

Emergence of diabetes mellitus in a Mexican-origin population: a multiple cause-of-death analysis.

The "New World syndrome" is comprised of disorders that are hypothesized to have resulted from an interaction of the Amerindian genotype with an environment that includes marked changes in lifestyle and diet. The principal component of the syndrome is adult-onset (noninsulin dependent) diabetes mellitus. The purpose of this paper is to describe the emergence of diabetes in a Mexican-origin population.

Why is catheter ablation less successful than surgery for treating ventricular tachycardia that results from coronary artery disease?

Nearly 80% of patients with coronary artery disease who have map-directed surgery for control of ventricular tachycardias require no drug therapy to prevent recurrences, while fewer than 50% of patients undergoing catheter ablation have similar outcomes. Catheter ablation will fail if arrhythmogenic sites are incompletely ablated by lesions that are too small or too far away from the reentrant pathway or if all arrhythmogenic sites are not identified. The underlying assumptions used to guide site selection are that: (a) ventricular tachycardias arise from reentrant mechanisms; (b) monomorphic ventricular tachycardias with similar QRS morphologies arise from the same pathway; (c) the ventricular tachycardia initiated during the procedure represents the patient's spontaneous arrhythmia; (d) the endocardial site that should be ablated can be identified from cardiac activation maps produced during induced ventricular tachycardia or from ancillary techniques; and (e) the patient has only one or two reentrant pathways.

Substrate specificity in short-chain phospholipid analogs at the active site of human synovial phospholipase A2.

The substrate specificity at the active site of recombinant human synovial fluid phospholipase A2 (hs-PLA2) was investigated by the preparation of a series of short-chain phospholipid analogs and measurement of their enzymatic hydrolysis at concentrations well below the critical micelle concentration. Substrates used in the study included 1,2-dihexanoylglycerophospholipids, 1,2-bis(alkanoylthio)glycerophospholipids, and 1-O-alkyl-2-(alkanoylthio)phospholipids. Turnover was observed for only a few of the 1,2-dihexanoylglycerophospholipids, and the rate of hydrolysis was very low, near the limit of detection of the assay.

Effects of peroneal nerve stimulation on hypothalamic stimulation-induced ventricular arrhythmias in rabbits.

We tested the hypothesis that peripheral afferent nerve stimulation decreases the incidence of ventricular arrhythmias induced by central nervous system stimulation. The hypothalamus in each of 24 anesthetized rabbits (12 with anterior myocardial ischemia) was electrically stimulated for 10 s with 10-min intervals between each of six consecutive stimulation episodes. The left peroneal nerves were electrically stimulated for 15 min beginning 5 min after the second hypothalamic stimulation episode in six ischemic and six nonischemic rabbits.

A fluorescence-based assay for human type II phospholipase A2.

A fluorescence assay for quantitation of human Type II Phospholipase A2 activity is described. Hydrolysis of 1-Acyl-2-(N-4-nitrobenzo-2-oxo-1,3-diazole)aminododecanoyl Phosphatidylethanolamine is accompanied by an increase in fluorescence intensity that is linearly proportional to enzyme activity. Substrate is prepared in the absence of detergents as a sonicated dispersion in aqueous buffer.

An automated technique for identification and analysis of activation fronts in a two-dimensional electrogram array.

Cardiac activation sequences are normally determined by (i) the detection and timing of local activations in cardiac electrograms, (ii) the grouping together of activations in different electrodes that are generated by the same activation fronts, and (iii) the construction by interpolation of isochronal maps showing the pathways of the activation fronts. This process is typically carried out by manual or semiautomated methods. These methods are usually adequate for stable, repeatable rhythms in normal hearts.

A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene.

The identification of mouse models for the various forms of human neurosensory non-syndromic recessive deafness would constitute a major advance in the study of human deafness. Here we describe the localization of a human gene for neurosensory, nonsyndromic recessive deafness (NSRD2) to chromosome 11q13.5 by linkage analysis of a highly consanguineous family.

Mechanisms of electrical defibrillation: impact of new experimental defibrillator waveforms.

Six possible explanations for why some biphasic waveforms have lower defibrillation thresholds than monophasic waveforms of the same duration are as follows: (1) the impedance for the second phase of the biphasic shock is very low because electrode polarization develops during the first phase; (2) the large change in voltage between the first and second phases of a biphasic waveform is responsible for the increased defibrillation efficacy; (3) biphasic waveforms cause less severe detrimental effects in regions of high potential gradient; (4) the first phase of the biphasic waveform restores activity of the sodium channels, which makes defibrillation easier for the second phase; (5) the potential gradient required for defibrillation is less for biphasic waveforms than for monophasic waveforms; and (6) biphasic waveforms are better able to stimulate the myocardium to induce new action potentials or to cause refractory period prolongation. Evidence shows that, while a few of these proposed mechanisms are incorrect, several of the others may together contribute to the general superiority of biphasic waveforms.

A non-syndrome form of neurosensory, recessive deafness maps to the pericentromeric region of chromosome 13q.

Non-syndromic, recessively inherited deafness is the most predominant form of severe inherited childhood deafness. Until now, no gene responsible for this type of deafness has been localized, due to extreme genetic heterogeneity and limited clinical differentiation. Linkage analyses using highly polymorphic microsatellite markers were performed on two consanguineous families from Tunisia affected by this form of deafness.

Maternal and congenital syphilis in Brooklyn, NY. Epidemiology, transmission, and diagnosis.

Objective: To define the epidemiology, to determine factors associated with transmission, and to describe the clinical and laboratory features of congenital syphilis.

Design: Retrospective chart review and prospective analysis.

Setting: Kings County Hospital Center, Brooklyn, NY.

Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome.

Kallmann syndrome represents the association of hypogonadotropic hypogonadism with anosmia. Three modes of transmission, X chromosome-linked, autosomal recessive and autosomal dominant, have been described. The KAL gene, responsible for the X-linked form of the disease, has been isolated and its intron-exon organization recently determined.

Variations in muscle chemical composition, pH, and protein extractability among eight different broiler crosses.

Variations in muscle chemical composition, pH, and protein extractability were studied using male broilers of eight different genetic crosses of commercial strains. Three replicate groups of 24 birds of each cross were grown in floor pens using commercial corn-soybean meal diets. At 8 wk of age, three birds per replicate, weighing within 5% of the pen average, were slaughtered, scalded, defeathered, eviscerated, and chilled in ice slurries overnight.

In vitro studies to investigate the reasons for the low potency of cholestyramine and colestipol.

The association rates, dissociation rates, and equilibrium binding of bile acids with cholestyramine and colestipol were measured under physiological conditions with the most abundant bile acids found in humans. Cholestyramine and colestipol equilibrated with the bile acids (5 mM) within 1 h and they bound > 58% and > 17% of the bile acid, respectively, when at equilibrium with physiological concentrations of bile acid (4.3-10.

Structure of the X-linked Kallmann syndrome gene and its homologous pseudogene on the Y chromosome.

The gene for the X-linked Kallmann syndrome (KAL), a developmental disorder characterized by hypogonadotropic hypogonadism and anosmia, maps to Xp22.3 and has a homologous locus, KALP, on Yq11. We show here that KAL consists of 14 exons spanning 120-200 kilobases that correlate with the distribution of domains in the predicted protein including four fibronectin type III repeats.

X chromosome-linked Kallmann syndrome: stop mutations validate the candidate gene.

Kallmann syndrome represents the association of hypogonadotropic hypogonadism with anosmia. This syndrome is from a defect in the embryonic migratory pathway of gonadotropin-releasing hormone synthesizing neurons and olfactory axons. A candidate gene for the X chromosome-linked form of the syndrome was recently isolated by using a positional cloning strategy based on deletion mapping in the Xp22.

Salivary IgA responses to Porphyromonas gingivalis in the cynomolgus monkey. 1. Total IgA and IgA antibody levels to P. gingivalis.

Porphyromonas gingivalis has been associated with the subgingival plaque of advancing disease lesions in various types of periodontitis. Additionally, this species of oral microorganism has been found to increase dramatically in ligature-induced periodontitis in nonhuman primates (Macaca fascicularis) and has recently been shown to induce progressing disease when implanted into the subgingival plaque in this animal model. Although systemic antibody responses have been demonstrated to P.

Attenuation of age-related conditioning deficits in humans by extension of the interstimulus interval.

Young (17-22 years) and older (61-86 years) persons underwent classical conditioning of the eye-blink response to a tone conditioned stimulus (CS) and an airpuff unconditioned stimulus (UCS) at 1 of 3 interstimulus intervals (ISIs; 400, 650, and 900 ms). As in a previous study, older subjects conditioned more slowly and emitted fewer conditioned responses at the optimal 400-ms ISI. At longer ISIs, however, this age-related disruption of classical conditioning was attenuated.