Mutations in the RP1 gene causing autosomal dominant retinitis pigmentosa.

Retinitis pigmentosa is a genetically heterogeneous form of retinal degeneration that affects approximately 1 in 3500 people worldwide. Recently we identified the gene responsible for the RP1 form of autosomal dominant retinitis pigmentosa (adRP) at 8q11-12 and found two different nonsense mutations in three families previously mapped to 8q. The RP1 gene is an unusually large protein, 2156 amino acids in length, but is comprised of four exons only.

Factors contributing to adverse soft tissue reactions due to the use of tartar control toothpastes: report of a case and literature review.

Tetrasodium and/or tetrapotassium pyrophosphate (Ppi) is the anticalculus component of most tartar control dentifrices on the market today. While pyrophosphates alone are not responsible for hypersensitivity reactions, several modifications which may lead to adverse oral manifestations may occur when pyrophosphates are added to a dentifrice. First, tetrasodium pyrophosphate in a dentifrice forms a slightly alkaline solution upon oral use which could irritate oral membranes.

Unraveling a cytoplasmic role for hnRNP D in the in vivo mRNA destabilization directed by the AU-rich element.

AU-rich RNA-destabilizing elements (AREs) have become a paradigm for studying cytoplasmic mRNA turnover in mammalian cells. Though many RNA-binding proteins have been shown to bind to AREs in vitro, trans-acting factors that participate in the in vivo destabilization of cytoplasmic RNA by AREs remains unknown. Experiments were performed to investigate the cellular mechanisms and to identify potential trans-acting factors for ARE-directed mRNA decay.

Autogenous regulation of the Bacillus anthracis pag operon.

Protective antigen (PA) is an important component of the edema and lethal toxins produced by Bacillus anthracis. PA is essential for binding the toxins to the target cell receptor and for facilitating translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. The structural gene for PA, pagA (previously known as pag), is located on the 182-kb virulence plasmid pXO1 at a locus distinct from the edema factor and lethal factor genes.

Middle range theory: spinning research and practice to create knowledge for the new millennium.

The foundation of middle range theory reported during the past decade was described and analyzed. A CINAHL search revealed 22 middle range theories that met selected criteria. This foundation is a firm base for new millennium theorizing.

Childhood and adolescent physical activity patterns and adult physical activity.

Purpose: A major research priority is the influence of childhood and adolescent physical activity patterns on adult physical activity. The research in this area is inconsistent. Therefore, the purpose of this study was to evaluate the relationships among specific components of physical activity during childhood and adolescence and exercise habits in adulthood.

Regulation of reactive oxygen species-induced apoptosis and necrosis by caspase 3-like proteases.

Reactive oxygen species (ROS) and caspases have been implicated as potential mediators of cell death. However, their mechanistic relationship remains to be elucidated. Here we investigated the roles of caspases in apoptosis and necrosis induced by ROS, generated by the mixture of xanthine and xanthine oxidase (X/XO).

Inhibition of mitochondrial respiratory chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis.

Mitochondria have been shown to play a key role in apoptosis induction. However, the sequence of changes that occur in the mitochondria in the initial step of apoptosis has not been clearly elucidated. Here, we showed that mitochondrial respiratory chain (MRC) complex I was inhibited during the early phase of TNF- or serum withdrawal apoptosis.

Cleavage of the C-terminus of NEDD8 by UCH-L3.

NEDD8 is a novel ubiquitin-like protein that has been shown to conjugate to nuclear proteins in a manner analogous to ubiquitination and sentrinization. To identify proteins that are involved in the NEDD8-conjugation and de-conjugation pathway, the yeast two-hybrid system was used to screen a human heart cDNA library using NEDD8 as a bait. Seven strongly positive clones were found to contain a cDNA insert encoding the ubiquitin C-terminal hydrolase, UCH-L3.

Ethnicity and adolescent depression: the case of Chinese Americans.

This paper is concerned with whether an instrument developed in the U.S. may identify lower rates of major depression among Chinese, because its content may not cover culture-specific symptoms of depression.

Identification of three major sentrinization sites in PML.

Acute promyelocytic leukemia arises following a reciprocal chromosome translocation t(15;17), which generates PML-retinoic acid receptor alpha fusion proteins (PML-RARalpha). We have shown previously that wild type PML, but not PML-RARalpha, is covalently modified by the sentrin family of ubiquitin-like proteins (Kamitani, T., Nguyen, H.

Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation.

Elevated blood pressure is an important risk factor for renal-, cerebro- and cardiovascular diseases. We used an efficient discordant sib-pair ascertainment scheme to investigate the impact of the distal end of the long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing genes for the alpha1B and beta2 adrenergic receptors and the dopamine receptor type 1A on variation of systolic blood pressure in young Caucasians.

Systemic lupus erythematosus in three ethnic groups: I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity at disease onset. LUMINA Study Group. Lupus in minority populations, nature versus nurture.

Objective: To study the relative impact of immunogenetic versus socioeconomic factors on systemic lupus erythematosus (SLE) at disease onset/presentation.

Methods: Medical records regarding SLE onset/ presentation were abstracted on 229 SLE patients who were enrolled in a prospective lupus outcome study. Patients were grouped in equivalent proportions of Caucasians, African Americans, and Hispanics.

Temporal relationships between de novo protein synthesis, calpain and caspase 3-like protease activation, and DNA fragmentation during apoptosis in septo-hippocampal cultures.

Caspase 3-like proteases are key executioners in mammalian apoptosis, and the calpain family of cysteine proteases has also been implicated as an effector of the apoptotic cascade. However, the influence of upstream events on calpain/caspase activation and the role of calpain/caspase activation on subsequent downstream events are poorly understood. This investigation examined the temporal profile of apoptosis-related events after staurosporine-induced apoptosis in mixed glial-neuronal septo-hippocampal cell cultures.

Black and white patients response to antidepressant treatment for major depression.

Differences in response to psychopharmacologic agents according to race has so far primarily focused on investigations related to the response of Asian-American patients to neuroleptics and lithium. In this article, we present evidence which depicts that black patients need lower doses of tricyclic antidepressants (TCAs) than white patients to attain a similar response in the treatment of major depression. Likewise, we also advance that black patients might need lower doses of selective serotonin re-uptake inhibitor antidepressants (SSRIs) than white patients to attain a similar response in the treatment of major depression.

Injury-coupled induction of endothelial eNOS and COX-2 genes: a paradigm for thromboresistant gene therapy.

Nitric oxide (NO) and prostacyclin (PGI2) are potent molecules produced by endothelial cells that act synergistically to maintain normal vascular functions. Recent studies indicate that key enzymes that catalyze the synthesis of these two molecules are induced by chemical and physical factors. Because NO and PGI2 and their synthetic enzymes have short half-lives, transcriptional induction by injurious agents, such as lysophosphatidylcholine (lysoPC), represents an important defense mechanism.

Dentin matrix proteins.

Dentinogenesis consists of highly controlled events occurring a short distance from the periphery of odontoblasts: it involves formation of extracellular collagen fibrils that act as an undergirding for deposition of plate-like carbonate apatite crystals. Odontoblasts also form a set of matrix proteins that are probably secreted at the mineralization front. Although most of these proteins are similar to those of bone, and differ from soft tissue proteins, dentin contains two unique proteins.

Salmeterol-induced desensitization, internalization and phosphorylation of the human beta2-adrenoceptor.

1. Partial agonists of the beta2-adrenoceptor which activate adenylyl cyclase are widely used as bronchodilators for the relief of bronchoconstriction accompanying many disease conditions, including bronchial asthma. The bronchodilator salmeterol has both a prolonged duration of action in bronchial tissue and the ability to reassert this activity following the temporary blockade of human beta2-adrenoceptors with antagonist.

Covalent modification of PML by the sentrin family of ubiquitin-like proteins.

PML, a RING finger protein with tumor suppressor activity, has been implicated in the pathogenesis of acute promyelocytic leukemia that arises following a reciprocal chromosomal translocation that fuses the PML gene with the retinoic acid receptor alpha (RARalpha) gene. Immunocytochemical analysis has demonstrated that PML is co-localized with a novel ubiquitin-like protein in the nuclear bodies, which could be disrupted by the PML-RARalpha fusion protein. The physical nature of this co-localization is unknown.

A broader role for AU-rich element-mediated mRNA turnover revealed by a new transcriptional pulse strategy.

The widespread occurrence of AU-rich elements (AREs) in mRNAs encoding proteins with diversified functions and synthesized under a vast variety of physiological conditions suggests that AREs are involved in finely tuned and stringent control of gene expression. Thus it is important to investigate the regulation of ARE-mediated mRNA decay in a variety of mammalian cells in different physiological states. The tetracycline (Tet)-regulatory promoter system appears appropriate for these investigations.

Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein.

NEDD8 is a novel 81 amino acid polypeptide which is 60% identical and 80% homologous to ubiquitin. Northern blot analysis showed that the NEDD8 message was developmentally down-regulated. In adult tissues, NEDD8 expression was mostly restricted to the heart and skeletal muscle.

Modulation of the fate of cytoplasmic mRNA by AU-rich elements: key sequence features controlling mRNA deadenylation and decay.

Regulation of cytoplasmic deadenylation has a direct impact on the fate of mRNA and, consequently, its expression in the cytoplasm. AU-rich elements (AREs) found in the 3' untranslated regions of many labile mRNAs are the most common RNA-destabilizing elements known in mammalian cells. AREs direct accelerated deadenylation as the first step in mRNA turnover.

Flow cytometric detection of Cryptosporidium oocysts in human stool samples.

Cryptosporidium parvum is an important pathogen that causes diarrhea in virtually all human populations. Improved diagnostic methods are needed to understand the risk factors, modes of transmission, and impact of cryptosporidiosis. In the present study, we fluorescently labeled and counted C.

Preferential modification of nuclear proteins by a novel ubiquitin-like molecule.

Sentrin is a novel ubiquitin-like protein that protects cells against both anti-Fas and tumor necrosis factor-induced cell death. Antiserum recognizing the N terminus of sentrin revealed the presence of a 18-kDa sentrin monomer, a 90-kDa band (p90), and multiple high molecular mass bands. Because sentrin possesses the conserved Gly-Gly residues near the C terminus, it is likely that these additional bands represent conjugation of sentrin to other proteins in a manner that is similar to the ubiquitination pathway.