Medicine and Health Sciences Commons^™

Priming Deficiency In Male Subjects At Risk For Alcoholism: The N4 During A Lexical Decision Task, Lance O. Bauer

UCHC Articles - Research

Abstract

Background

While there is extensive literature on the relationship between the P3 component of event-related potentials (ERPs) and risk for alcoholism, there are few published studies regarding other potentially important ERP components. One important candidate is the N4(00) component in the context of semantic processing, as abnormalities in this component have been reported for adult alcoholics.

Method

A semantic priming task was administered to non-alcohol dependent male offspring (18 to 25 years) of alcoholic fathers [high risk (HR) n=23] and non-alcoholic fathers [low risk (LR) n=28], to study whether the two groups differ in terms of the N4 component. …

Effect Of Hcv Rna Suppression During Peginterferon Alfa-2a Maintenance Therapy On Clinical Outcomes In The Halt-C Trial, Herbert L. Bonkovsky

UCHC Articles - Research

Background and Aims

The HALT-C trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine if suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes.

Methods

764 patients treated during the lead-in phase of HALT-C were randomized to either peginterferon alfa-2a (90 mcg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites, spontaneous …

Alcohol Use And Gender Effects On Hiv Risk Behaviors In Cocaine-Using Methadone Patients, Carla J. Rash, Nancy M. Petry

UCHC Articles - Research

Injection drug users engage in behaviors that increase the spread of human immunodeficiency virus (HIV) and other infectious diseases. Although methadone maintenance (MM) is highly effective in decreasing heroin use and the spread of HIV, polydrug use, especially the combined use of cocaine and alcohol, is common in MM patients. Alcohol use is independently associated with HIV risk behaviors, and the effects of alcohol use on risk behaviors may vary by gender. This study evaluated the effects of recent heavy alcohol use and gender with respect to HIV risk behaviors in 118 cocaine-abusing methadone patients. Both lifetime and past month …

Individualized Assessment And Treatment Program For Alcohol Dependence: Results Of An Initial Study To Train Coping Skills, Mark D. Litt, Ronald M. Kadden, Elise Kabela-Cormier

UCHC Articles - Research

Cognitive-behavioral treatments (CBT) are among the most popular interventions offered for alcohol and other substance use disorders, but it is not clear how they achieve their effects. CBT is purported to exert its beneficial effects by altering coping skills, but data supporting coping changes as the mechanism of action are mixed. The purpose of this pilot study was to test a treatment in which coping skills were trained in a highly individualized way, allowing us to determine if such training would result in an effective treatment. Conclusions The IATP approach was more successful than PCBT at training adaptive coping responses …

Rna-Guided Rna Cleavage By A Crispr Rna-Cas Protein Complex, Brenton R. Graveley, Sara Olson, Michael O. Duff

UCHC Articles - Research

Compelling evidence indicates that the CRISPR-Cas system protects prokaryotes from viruses and other potential genome invaders. This adaptive prokaryotic immune system arises from the clustered regularly interspaced short palindromic repeats (CRISPRs) found in prokaryotic genomes, which harbor short invader-derived sequences, and the CRISPR-associated (Cas) protein-coding genes. Here we have identified a CRISPR-Cas effector complex that is comprised of small invader-targeting RNAs from the CRISPR loci (termed prokaryotic silencing (psi)RNAs) and the RAMP module (or Cmr) Cas proteins. The psiRNA-Cmr protein complexes cleave complementary target RNAs at a fixed distance from the 3' end of the integral psiRNAs. In Pyrococcus furiosus …

Control Of Electrochemical And Ferryloxy Formation Kinetics Of Cyt P450s In Polyion Films By Heme Iron Spin State And Secondary Structure, Sadagopan Krishnan, Amila Abeykoon, John B. Schenkman, James F. Rusling

UCHC Articles - Research

Voltammetry of cytochrome P450 (cyt P450) enzymes in ultrathin films with polyions was related for the first time to electronic and secondary structure. Heterogeneous electron transfer (hET) rate constants for reduction of the cyt P450s depended on heme iron spin state, with low spin cyt P450cam giving a value 40-fold larger than high spin human cyt P450 1A2, with mixed spin human P450 cyt 2E1 at an intermediate value. Asymmetric reduction–oxidation peak separations with increasing scan rates were explained by simulations featuring faster oxidation than reduction. Results are consistent with a square scheme in which oxidized and reduced forms of …

Increased Drinking In A Trial Of Treatments For Marijuana Dependence: Substance Substitution?, Ronald M. Kadden, Mark D. Litt, Elise Kabela-Cormier, Nancy M. Petry

UCHC Articles - Research

This report examines whether participants in a study of treatments for marijuana dependence may have increased their use of alcohol when they reduced or ceased marijuana use. Participants were randomly assigned to one of four psychosocial treatments and followed at 3-month intervals for one-year. Findings are from 207 cases with data at posttreatment and at least one other follow-up. 73% of cases reported an increase of at least 10% in drinking days over their level at intake, and 65% reported an increase of at least 10% in drinks per drinking day. Drinking increases were not related to treatment condition nor …

Neuropeptide Y Is Expressed By Osteocytes And Can Inhibit Osteoblastic Activity, John C. Igwe, Xi Jiang, Frane Paic, Li Ma, Douglas J. Adams, Carol C. Pilbeam, Ivo Kalajzic

UCHC Articles - Research

Osteocytes are the most abundant osteoblast lineage cells within the bone matrix. They respond to mechanical stimulation and can participate in the release of regulatory proteins that can modulate the activity of other bone cells. We hypothesize that neuropeptide Y (NPY), a neurotransmitter with regulatory functions in bone formation, is produced by osteocytes and can affect osteoblast activity. To study the expression of NPY by the osteoblast lineage cells, we utilized transgenic mouse models in which we can identify and isolate populations of osteoblasts and osteocytes. The Col2.3GFP transgene is active in osteoblasts and osteocytes, while the DMP1 promoter drives …

Effects Of Nicotine Patch Or Nasal Spray On Nicotine And Cotinine Concentrations In Pregnant Smokers, Cheryl A. Oncken, Winston A. Campbell, Grace Chan, Henry R. Kranzler

UCHC Articles - Research

Objective To examine the short-term effects of the nicotine patch or nasal spray on measures of nicotine exposure, withdrawal symptoms, and on maternal and fetal heart rates in pregnant smokers. Methods We measured nicotine/cotinine concentrations and maternal and fetal heart rates during an 8-hour monitoring session while smoking and again after 4 days of nicotine patch (15 mg/16 hours), nasal spray (recommended regimen of 24 doses per day), or placebo treatment. Nicotine withdrawal symptoms were assessed daily. Results Twenty-one subjects, who smoked an average of 17 cigarettes per day, completed both monitoring sessions. Nicotine concentrations decreased from baseline smoking concentrations …

Weight-Related Effects On Disease Progression In The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial, Herbert L. Bonkovsky

UCHC Articles - Research

BACKGROUND & AIMS With the limited efficacy of current therapy for chronic hepatitis C, modifiable risk factors for liver disease progression are important to identify. Because obesity is associated with liver disease, we examined the effects of weight-related conditions on disease outcomes in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. METHODS Of 1050 patients, 985 could be evaluated for predefined progression of liver disease not related to hepatocellular carcinoma. Clinical outcomes were determined over 3.5 years for all patients and progression to cirrhosis on protocol biopsy among patients who had bridging fibrosis (56.5% of cohort) at entry. …

The Buffering Effect Of Hope On Clinicians’ Behavior: A Test In Pediatric Primary Care, Howard A. Tennen, Michelle M. Cloutier, Dorothy B. Wakefield

UCHC Articles - Research

Although trait hope is thought to motivate goal directed actions in the face of impediments, few studies have examined directly hope’s role in overcoming obstacles, and none have done so while accounting for related goal constructs. We describe a study of 127 pediatric primary care providers who over the course of a year were asked to identify new cases of asthma and confirm previously diagnosed active disease by completing for each of their patients a brief survey validated for this purpose. These clinicians also completed measures of hope, self-efficacy, conscientiousness, and perceived obstacles to implementing a pediatric asthma management program. …

Clock-Cancer Connection In Non-Hodgkin’S Lymphoma: A Genetic Association Study And Pathway Analysis Of The Circadian Gene Cryptochrome 2, Richard G. Stevens

UCHC Articles - Research

Circadian genes have the potential to influence a variety of cancer-related biological pathways, including immune regulation, which may influence susceptibility to non-Hodgkin’s lymphoma (NHL). However, few studies have examined the role of circadian genes in lymphomagenesis. The current study examined Cryptochrome 2 (CRY2), a core circadian gene and transcriptional repressor, as a potential circadian biomarker for NHL. We first performed genetic association analyses of tagging SNPs in CRY2 and NHL risk using DNA samples from a population-based case-control study (N= 455 cases and 527 controls). Three SNPs were found to be significantly associated with risk of NHL when …

A Common Polymorphism In Serotonin Receptor 1b Mrna Moderates Regulation By Mir-96 And Associates With Aggressive Human Behaviors, Kevin P. Jensen, Jonathan Covault, Tamlin S. Conner, Henry R. Kranzler, Howard A. Tennen, Henry M. Furneaux

UCHC Articles - Research

Non-coding regulatory elements can transduce the human genome's response to environmental stimuli. Thus, there is a possibility that variation in non-coding regulatory elements may underlie some of the diversity in human behavior. However, this idea has remained largely untested due to the difficulty in accurately identifying regulatory elements in the 98% of the human genome that does not encode protein. The recent recognition that small trans-acting RNAs anneal to mRNA and regulate gene expression provides a means to identify and test such variants. Here we show that microRNA-directed silencing of mRNA can be attenuated by a common human polymorphism. We …

Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptor 2 Signaling Induces Cox-2 Expression In Wilms Tumor, Mei-Hong Li, Teresa Sanchez, Timothy Hla, Fernando Ferrer

UCHC Articles - Research

Purpose

Cyclooxygenase-2 (COX-2) has been reported to be ubiquitously expressed in Wilms tumor, the most common malignant renal tumor in children. However, the regulation mechanism of COX-2 expression remains unexplored.

Materials and Methods

Quantitative real-time PCR and western blot analysis were performed to detect COX-2 mRNA and protein expression in WiT49 cells upon the stimulation by sphingosine-1-phosphate (S1P) as well as S1P₂ and COX-2 mRNA expression in 10 fresh frozen Wilms tumor tissues and their matched normal tissues. Overexpression, blockade and downregulation of S1P₂ were performed using adenoviral transduction, S1P₂ antagonist JTE-013 and siRNA transfection, respectively. The …

A Rapid Non-Destructive Method For Root Dentin Moisture Measurements, Qiang Zhu, Jin Jiang, Kamran E. Safavi, Larz S.W. Spångberg

UCHC Articles - Research

Dentin moisture content is important in adhesive bonding and structural strength research. However, there is no rapid method available to assess dentin moisture without sample destruction. This study examined the use of a digital grain moisture meter to measure root dentin moisture in vitro. Extracted mandibular single rooted teeth were sectioned at the CEJ. The moisture of the root dentin was measured at six measuring modes for different grains and repeated five times. Dentin weight changes before and after drying were measured to obtain control values. The control values were compared with machine readings. In conclusion, (1) Each non-destructive measurement …

Retention Of Polarization Signatures In Shg Microscopy Of Scattering Tissues Through Optical Clearing, Oleg Nadiarnykh, Paul J. Campagnola

UCHC Articles - Research

Polarization responses in Second Harmonic Generation (SHG) imaging microscopy are a valuable method to quantify aspects of tissue structure, and may be a means to differentiate normal and diseased tissues. Due to multiple scattering, the polarization data is lost in turbid tissues. Here we investigate if this information can be retained through the use of optical clearing which greatly reduces the scattering coefficient and increases the corresponding mean free path. To this end, we have measured the SHG intensity as a function of laser polarization and the SHG signal anisotropy in murine tendon and striated muscle over a depth range …

Alcohol In Moderation, Cardioprotection And Neuroprotection : Epidemiological Considerations And Mechanistic Studies, Dipak K. Das Dr.

UCHC Articles - Research

In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating beneficial effects of light-moderate, non-binge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate …

Identification Of Novel Tumor Antigens With Patient-Derived Immune-Selected Antibodies, Daniel Rodriguez-Pinto, Martin P. Keough, Kathryn N. Phoenix, Frank Vumbaca, David K. K. Han, Kevin P. Claffey

UCHC Articles - Research

The identification of tumor antigens capable of eliciting an immune response in vivo may be an effective method to identify therapeutic cancer targets. We have developed a method to identify such antigens using frozen tumor-draining lymph node samples from breast cancer patients. Immune responses in tumor-draining lymph nodes were identified by immunostaining lymph node sections for B-cell markers (CD20&CD23) and Ki67 which revealed cell proliferation in germinal center zones. Antigen-dependent somatic hypermutation (SH) and clonal expansion (CE) were present in heavy chain variable (VH) domain cDNA clones obtained from these germinal centers, but not from Ki67 negative germinal centers. Recombinant …

Human Cyt P450 Mediated Metabolic Toxicity Of 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (Nnk) Evaluated Using Electrochemiluminescent Arrays, Sadagopan Krishnan, Besnik Bajrami, John B. Schenkman, James F. Rusling

UCHC Articles - Research

Electrochemiluminescent (ECL) arrays containing polymer ([Ru(bpy)₂(PVP)₁₀]²⁺, PVP = polyvinylpyridine), DNA, and selected enzymes were employed to elucidate cytochrome (cyt) P450 dependent metabolism of the tobacco specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Bioactivated NNK metabolites formed upon H₂O₂-enzymatic activation were captured as DNA adducts and detected simultaneously from 36 spot arrays by capturing and quantifying emitted ECL with an overhead CCD camera. Increased ECL emission was dependent on NNK exposure time. Of the enzymes tested, the activity toward NNK bioactivation was cyt P450 1A2 > 2E1 > 1B1 ≈ chloroperoxidase (CPO) > myoglobin (Mb) in accordance …

Validity Testing The Outcomes And Assessment Information Set (Oasis), Richard H. Fortinsky

UCHC Articles - Research

This study evaluated the criterion validity of the Outcome and Assessment Instrument Set (OASIS) items that measure activities of daily living (ADLs), instrumental activities of daily living (IADLs), cognitive functioning, and depression. A convenience sample of patients (n = 203) from five home care agencies participated in the study. Patient OASIS items were compared to data collected using gold standard instruments. Correlations range from .44 to .69 for ADLs and .20 to .68 for IADLs. A correlation of .62 was found for cognitive functioning while correlations for depressive symptoms are .36 and .26. OASIS ADLs and cognitive status items are …

Regulation Of The Prostaglandin Pathway During Development Of Invasive Bladder Cancer In Mice, John A. Taylor Iii, Benjamin Ristau, Mathilde Bonnemaison, Olga S. Voznesensky, Poornima Hegde, George A. Kuchel, Carol C. Pilbeam

UCHC Articles - Research

Prostaglandin E₂ (PGE₂) is reported to play an important role in tumor development. We explored the differential expression of genes governing production of, and response to, PGE₂ during development of invasive bladder cancer. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) or vehicle-treated mice (n = 4–5) were euthanized after 4–8 weeks (period 1, P1), 12–16 weeks (P2), and 20–23 weeks (P3). Half of each bladder was analyzed histologically and the other half extracted for mRNA analysis by quantitative real-time PCR. Bladders from BBN-treated mice showed progression from submucosal inflammation (P1) to squamous metaplasia/focal CIS (P2) to poorly …

Microinjection Of Follicle-Enclosed Mouse Oocytes, Laurinda A. Jaffe, Rachael P. Norris, Marina Freudzon, William J. Ratzan, Lisa M. Mehlmann

UCHC Articles - Research

The mammalian oocyte develops within a complex of somatic cells known as a follicle, within which signals from the somatic cells regulate the oocyte, and signals from the oocyte regulate the somatic cells. Because isolation of the oocyte from the follicle disrupts these communication pathways, oocyte physiology is best studied within an intact follicle. Here we describe methods for quantitative microinjection of follicle-enclosed mouse oocytes, thus allowing the introduction of signaling molecules as well as optical probes into the oocyte within its physiological environment.

Incidence Of Hepatocellular Carcinoma And Associated Risk Factors In Hepatitis C-Related Advanced Liver Disease, Herbert L. Bonkovsky

UCHC Articles - Research

Background and Aims

Although the incidence of hepatocellular carcinoma (HCC) is increasing in the United States, data from large prospective studies are limited. We evaluated the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) cohort for the incidence of HCC and associated risk factors.

Methods

HCV-positive patients with bridging fibrosis or cirrhosis that did not respond to peginterferon and ribavirin were randomized to groups that were given maintenance peginterferon for 3.5 years or no treatment. HCC incidence was determined by Kaplan-Meier analysis and baseline factors associated with HCC were analyzed by Cox regression.

Results

1,005 patients (mean age 50.2 years, …