A novel likely pathogenic variant in a patient with Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by oculocutaneous albinism and variable pulmonary fibrosis, granulomatous colitis, or immunodeficiency. The diagnosis relies on clinical findings, platelet transmission electron microscopy studies showing absent dense granules, or the identification of a pathogenic genotype in one of 11 associated genes, including We report a 2-wk-old male with significant iris transillumination defects, a pale fundus, and mild corectopia found by clinical exome sequencing to have a previously reported pathogenic variant, c.972dupC p.

The effect of indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis.

Objectives: Acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is a severe complication with substantial morbidity and mortality. Indomethacin has been identified to prevent this complication; however, the results using indomethacin have varied. Therefore, we performed a meta-analysis on the efficacy of rectally administered indomethacin in the prevention of post-ERCP pancreatitis (PEP).

Deceptively benign low-grade fibromyxoid sarcoma: array-comparative genomic hybridization decodes the diagnosis.

Low-grade fibromyxoid sarcoma (previously known as Evans tumor) is a rare soft tissue neoplasm characterized by a deceptively bland appearance despite the potential for late metastasis or recurrence. We describe a 13-year-old patient with a popliteal fossa mass initially thought to be benign that, because of array-comparative genomic hybridization findings and subsequent immunohistochemistry, was diagnosed as low-grade fibromyxoid sarcoma. The array-comparative genomic hybridization demonstrated a loss of 11p11.

Colonic in situ mantle cell lymphoma.

This report describes the first case, to our knowledge, of in situ mantle cell lymphoma (MCL) in the gastrointestinal tract identified retrospectively by immunostains and fluorescence in situ hybridization (FISH) analysis after progression to disseminated disease with pleomorphic morphology several years later. A 45-year-old man with blood per rectum underwent colonoscopy and had random biopsies interpreted as benign colonic mucosa. Two years later, he presented with ileocolic intussusception related to enlarged lymph nodes.

Association of SOD2, a mitochondrial antioxidant enzyme, with gray matter volume shrinkage in alcoholics.

Chronic alcoholism leads to gray matter shrinkage and induces the formation of superoxide anions (O(2)(-)) that can cause neuronal cell death. The mitochondrial superoxide dismutase 2 (SOD2) enzyme is critical in the metabolism of superoxide. An Ala16Val polymorphism putatively affects SOD2 enzyme activity in vivo.

OPRM1 Asn40Asp predicts response to naltrexone treatment: a haplotype-based approach.

Background: Individualized pharmacotherapy requires identification of genetic variants predictive of treatment response. In OPRM1, Asn40Asp has been reported to be predictive of response to naltrexone treatment. Nevertheless, the in vitro function of the polymorphism remains elusive and over 300 OPRM1 sequence variants have been identified to date.

An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study.

Context: Naltrexone hydrochloride treatment for alcohol dependence works for some individuals but not for everyone. Asn40Asp, a functional polymorphism of the mu-opioid receptor gene (OPRM1), might predict naltrexone response.

Objective: To evaluate whether individuals with alcoholism who are heterozygous (Asp40/Asn40) or homozygous (Asp40/Asp40) for the OPRM1 Asp40 allele respond better to naltrexone.

Association of THR105Ile, a functional polymorphism of histamine N-methyltransferase (HNMT), with alcoholism in German Caucasians.

Background: CNS histamine has been shown to have an inhibitory effect on reward and it is implicated in the etiology of addiction and stress. Histamine N-methyltransferase (HNMT) is believed to be the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain. A common, functional polymorphism, a C314T transition in the HNMT gene, results in a Thr105Ile substitution of the protein encoded.

Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen.

Epidemiological studies demonstrated that even in the absence of other risk factors (e.g. diabetes, hypertension, hyperhomocysteinemia, hypercholesterolemia), advanced age itself significantly increases cardiovascular morbidity by enhancing vascular oxidative stress and inflammation.

The Met66 allele of the functional Val66Met polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in systemic lupus erythematosus.

Background: A common functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) was previously associated with diminished episodic memory performance in healthy people. As cognitive function is commonly impaired in patients with systemic lupus erythematosus (SLE), the association of the BDNF Val66Met with neurocognitive function was studied.

Objective: To study the association of the BDNF Val66Met with neurocognitive function in a cohort of patients with SLE.

COMBINE genetics study: the pharmacogenetics of alcoholism treatment response: genes and mechanisms.

Objective: Partial efficacy of treatment and differences in adverse events across individuals are a challenge and an opportunity in the treatment of alcoholism. Individuation of therapy and understanding origins of differential treatment response may require identification of inherited functional variants of genes. The neurobiology of reward, executive cognitive function, anxiety and dysphoria have been identified as critical domains that may have a genetic basis that could predict treatment response.

The genetics of addictions: uncovering the genes.

The addictions are common chronic psychiatric diseases that today are prevented and treated using relatively untargeted and only partially effective methods. The addictions are moderately to highly heritable, which is paradoxical because these disorders require use; a choice that is itself modulated by both genes and environment. The addictions are interrelated and related to other psychiatric diseases by common neurobiological pathways, including those that modulate reward, behavioural control and the anxiety or stress response.

Thr105Ile, a functional polymorphism of histamine N-methyltransferase, is associated with alcoholism in two independent populations.

Background: Histamine is expressed in cortical and limbic areas that are involved in emotion and cognition and modulates these behaviors. H1 receptor antagonists are sedative. Histamine N-methyltransferase (HNMT) catalyzes the Ntau methylation of histamine, the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain.

An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk.

Background: Alcoholism is a complex, genetically influenced disorder the cause of which may be better understood through the study of genetically influenced phenotypes that mediate the risk. One such intermediate phenotype is the low level of response (LR) to alcohol. This project used a case-control approach to search for genes that may contribute to LR.

Alcoholism: genes and mechanisms.

Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction.

Distribution of PACAP-38 in the central nervous system of various species determined by a novel radioimmunoassay.

Pituitary adenylate cyclase activating polypeptide (PACAP) occurs in two molecular forms: PACAP-38 and PACAP-27. Soon after the isolation and chemical characterization of PACAP, the first radioimmunoassay (RIA) methods have been developed, but it is a still rarely used laboratory technique in the field of PACAP research. The aim of the present study was to develop a novel, highly specific PACAP-38 assay to investigate the quantitative distribution of PACAP-38 in the central nervous system of various vertebrate species under the same technical and experimental conditions.

Role of voltage-gated cation channels and axon reflexes in the release of sensory neuropeptides by capsaicin from isolated rat trachea.

In order to reveal the role of axon reflexes and sensory receptors in sensory neuropeptide release in response to capsaicin, liberation of substance P, calcitonin gene-related peptide and somatostatin from isolated rat tracheae was investigated in the presence of voltage-sensitive Na(+) and Ca(2+) channel blocking agents. Neuropeptide release induced by capsaicin (10 nM) remained unchanged in the presence of 25 mM lidocaine, 1 microM tetrodotoxin or the N-type Ca(2+) channel inhibitor, omega-conotoxin GVIA (100-300 nM). Peptide release by 100 pulses of 2 Hz field stimulation was prevented by lidocaine or tetrodotoxin.

Impaired capsaicin-induced decrease in heart rate and coronary flow in isolated heart of diabetic rats.

The effect of capsaicin (0.1 microM) on heart rate and coronary flow was studied in Langendorff-perfused heart from streptozotocin-induced (50 mg/kg i.v.

Anti-inflammatory effect of synthetic somatostatin analogues in the rat.

1. Somatostatin (6.11 nmol kg(-1) i.

Functional and biochemical evidence for capsaicin-induced neural endothelin release in isolated working rat heart.

In isolated working rat heart, capsaicin elicited a concentration-dependent constriction of coronary arteries accompanied by decline of all cardiac parameters recorded (heart rate, coronary and aortic flow, left ventricular developed pressure, and first derivative of left ventricular developed pressure). The following evidence suggests that capsaicin-induced changes are mediated by endothelin of neural origin: (1) the capsaicin (10 nM)-evoked decrease in coronary flow resulting in deterioration of cardiac functions was mimicked by endothelin (0.1 nM); (2) the selective endothelin ET(A) receptor antagonist, cyclo (D-alpha-aspartyl-L-propyl-D-valyl-L-leucyl-D-tryptophyl) (1 microM), abolished the cardiac effects provoked by capsaicin (10 nM); (3) reduction of extracellular Ca2+ concentration from 2.

Substance P radioimmunoassay for quantitative characterization of sensory neurotransmitter release.

In the present work we report the development of a new radioimmunoassay method for measuring the substance P content liberated from isolated rat tracheae in response to electrical or chemical (capsaicin, resiniferatoxin, piperine) stimulation. The amount of substance P released by electrical stimulation has been found to be dependent on the number of pulses and chemically elicited substance P release also proved to be dose-dependent. Our findings reinforce previous data that resiniferatoxin is approximately 100 times more potent than capsaicin and the potency ratio between piperine and capsaicin is 1/50.