bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanisms of cis‐urocanic acid and permethrin‐induced alterations in cutaneous immunity
Authors: Prater M. R. , Blaylock B. L. , Holladay S. D. 
Published: November 2003

Background/Purpose: Cutaneous cis‐urocanic acid (cUCA) or ultraviolet B exposure has been shown to cause diminished cutaneous contact hypersensitivity (CH) and to induce systemic tolerance (increased regulatory T lymphocytes) in mice. Permethrin is also a known CH inhibitor, but the molecular mechanisms are currently poorly understood. In this study, CH was evaluated in four strains of mice: an immunosensitive strain (C57BL/6N), an immunoresistant strain (SvImJ), a strain developed from C57BL/6N mice but genetically altered at both the tumor necrosis factor‐alpha receptors (TNFαp55R and p75R), and a strain developed from C57BL/6N but genetically deleted at the interferon‐gamma (IFNγ) locus.Methods: CH was evaluated in each group via oxazolone challenge following a 5‐day exposure to intradermal (ID) cUCA or a single exposure to topical permethrin, or co‐exposure to both chemicals in 5‐week‐old female C57BL/6N, SvImJ, and C57BL/6N mice genetically altered at the TNFα or IFNγ locus.Results: A 5‐day exposure to ID cUCA or a single exposure to topical permethrin resulted in diminished CH response in C57BL/6N mice, and this effect was exacerbated with concurrent exposure to both chemicals. CH in SvImJ was both cUCA‐ and permethrin‐resistant relative to C57BL/6N mice, as 5‐day cUCA or a single exposure to permethrin did not diminish CH, nor did concurrent exposure to cUCA and permethrin. Mice deleted at both TNFαR loci displayed similar but somewhat blunted diminished CH responses to cUCA or permethrin. This trend became significant with combined chemical exposure. IFNγ knockout mice displayed similar diminished CH responses to cUCA or permethrin alone. Unlike C57BL/6N mice, the IFNγ knockout mice did not show a further reduction in CH with combined chemical exposure.Conclusions: These results suggest the following:

Mouse strains show variable susceptibility to permethrin‐ and cUCA‐induced immunomodulation.
TNFα may be involved in the immunomodulatory effects of cUCA and permethrin.
IFNγ may be required for the more than additive depression of CH caused by cUCA+permethrin.
Effects of a melanogenic bicyclic monoterpene diol on cell cycle, p53, TNF‐α, and PGE2 are distinct from those of UVB
Authors: Kraus Eliyahu , Galvin Jason W. , Boumakis Stavroula , Boamah Ernest K. , Canning Matthew T. , Yarosh Daniel B. , Brown David A. 
Published: November 2003

Purpose: Bicyclic monoterpene (BMT) diols are small‐molecule compounds that mimic ultraviolet radiation (UVR) by inducing melanogenesis. The objective of this study was to compare the effects of 2,2‐dimethyl‐3‐propanyldiol‐norbornane (AGI‐1140), a novel BMT diol, and ultraviolet B (UVB) on additional cellular responses.Methods: S91 mouse melanoma cells were treated with a range of concentrations of AGI‐1140, and examined for induction of melanogenesis and nitric oxide (NO). The effect of AGI‐1140 on dendrite outgrowth from human melanocytes was examined by quantitative microscopy. The effect of AGI‐1140 and UVB on phosphorylation of p53 serine 15 in human keratinocytes was examined by Western blotting, while the release of tumor necrosis factor‐α (TNF‐α) and prostaglandin E2 (PGE2) was determined by enzyme‐linked immunosorbent assay. The effects of AGI‐1140 and UVB on cell cycle arrest of human melanocytes, keratinocytes, fibroblasts, and endothelial cells were compared using fluorescence‐activated cell sorting.Results: Similar to UVB, AGI‐1140 induced both melanogenesis and NO in melanoma cells. AGI‐1140 also induced dendrite outgrowth from melanocytes, indicative of differentiation. However, whereas UVB induced G2 cell cycle arrest with phosphorylation of p53 at serine 15, AGI‐1140 induced G1 cell cycle arrest without this phosphorylation. Additionally, unlike UVB, AGI‐1140 did not increase the secretion of TNF‐α or PGE2, mediators of UVB‐induced immunosuppressive and inflammatory responses in the skin that may contribute to carcinogenesis.Conclusion: This study shows that melanogenesis can be induced by AGI‐1140 without many of the deleterious effects associated with UVB.
Family History of Alcoholism and Response to Sweets
Authors: Kampov‐Polevoy Alexey B. , Garbutt James C. , Khalitov Elena 
Published: November 2003

Background: The relationship between a hedonic response to sweet tastes and a propensity to excessive alcohol drinking is supported by both animal and human studies. This study was designed to test the hypothesis that the genetic risk for alcoholism as measured by a paternal history of alcoholism in young social drinkers is associated with sweet‐liking, defined as rating the strongest offered sucrose solution (i.e., 0.83 M) as the most palatable during the standard sweet test.Methods: Participants were 163 subjects (39% male) without a lifetime history of alcohol or drug abuse or dependence. Eighty‐one subjects had a paternal history of alcoholism (FH+), and 82 did not (FH−). Each subject rated a series of sucrose solutions for intensity of sweetness and palatability. Subjects were categorized as sweet‐likers if they rated the highest sucrose concentration as the most pleasurable.Results: The estimated odds of being a sweet‐liker were 2.5 times higher for FH+ than for FH− subjects. FH+ subjects disliked the tastes of the two weakest offered sucrose concentrations (0.05 and 0.10 M), whereas FH− subjects reported these tastes to be neutral.Conclusions: The results of this study support the hypothesis that sweet‐liking is associated with a genetic vulnerability to alcoholism.
Role of Nitric Oxide in Alcohol Alteration of β‐Endorphin Release From Hypothalamic Cells in Primary Cultures
Authors: Boyadjieva Nadka I. , Chen Cui P. , Sarkar Dipak K. 
Published: November 2003

Background: Nitric oxide (NO) mediates many pharmacological actions of ethanol. NO's role in regulating ethanol action on hypothalamic β‐endorphin (β‐EP) neurons is not established.Methods: In this study, we determined the role of NO in ethanol regulation of β‐EP release from primary cultures of rat fetal mediobasal hypothalamic cells. Real‐time polymerase chain reaction was used for messenger RNA (mRNA) detection; radioimmunoassay was used for hormone measurements.Results: Acute ethanol treatment for 3 hr increased the release of β‐EP but reduced nitrite levels in the media of hypothalamic cells in primary cultures. In contrast, ethanol exposure for 48 hr reduced the release of β‐EP but increased the release of nitrite from these cells. Alcohol treatments altered the expression of neuronal NO synthase mRNA, but not inducible NO synthase mRNA, in a pattern similar to that of nitrite levels. Alcohol treatments blocked sodium nitroprusside–induced increases in the level of cellular cyclic guanidine monophosphate. The nonspecific NO blocker NG‐nitro‐l‐arginine‐methyl‐esther, but not the inactive isomer N‐nitro‐d‐arginine‐methyl‐esther (d‐NAME), inhibited ethanol inhibitory actions on β‐EP release.Conclusions: These results suggest that the cyclic guanidine monophosphate/NO pathway is involved in ethanol alteration of hypothalamic β‐EP release.
Leptin and Cellular and Innate Immunity in Abstinent Alcoholics and Controls
Authors: Motivala Sarosh J. , Dang Jeff , Obradovic Tanja , Meadows Gary G. , Butch Anthony W. , Irwin Michael R. 
Published: November 2003

Background: Basic studies indicate that in vitro and in vivo doses of leptin modulate cellular immune responses. Given evidence that concentrations of leptin are altered in alcoholics who also show immune abnormalities, this study examined the relationships between circulating levels of leptin and markers of cellular and innate immunity.Methods: Circulating levels of leptin, natural killer cell (NK) activity, interleukin‐2 (IL‐2)–stimulated NK activity, and concanavalin A–stimulated production of IL‐2, IL‐6, IL‐10, and IL‐12 were compared between abstinent DSM‐IV alcohol‐dependent men (n= 27) and age‐ and gender‐matched controls (n= 34).Results: As compared with controls, alcoholics showed lower NK activity (p < 0.01) and a trend for lower levels of leptin (p= 0.055). In the total sample, leptin predicted NK activity (β= 0.33; p < 0.05) after controlling for the confounding influence of body mass index, alcohol intake, and smoking. Leptin was not correlated with any of the cytokine measures. To examine whether the effects of leptin were mediated by its direct action on NK, additional studies examined in vitro effects of leptin on NK activity in healthy volunteers (n= 10); leptin doses (0.1, 1, and 10 nM) yielded levels of NK activity comparable to those with media alone.Conclusions: These data show that circulating levels of leptin are associated with NK activity in humans and suggest that abnormal in vivo concentrations of leptin may contribute to the declines of NK activity in alcoholics who are at risk for infectious diseases.
Specific Alteration of Peripheral Cytotoxic Cell Perforin Expression in Alcoholic Patients: A Possible Role in Alcohol‐Related Diseases
Authors: Perney Pascal , Portalès Pierre , Corbeau Pierre , Roques Valérie , Blanc François , Clot Jacques 
Published: November 2003

Background: The association between chronic alcohol consumption and an increasing risk of infectious and neoplastic disease is related to an impairment of cellular immunity. However, studies of the number and activity of lymphocyte subsets show highly variable results. The aim of this study was to assess the expression of perforin, one of the main molecular agents of T and natural killer (NK) cell–mediated cytotoxicity, in alcoholic patients without cirrhosis.Methods: Eighteen patients with chronic alcoholism were prospectively included and compared with 18 age‐ and sex‐matched healthy volunteers. Signs of hepatic insufficiency or portal hypertension, viral co‐infection, other serious medical illness, and immune‐related medications were exclusion criteria. Lymphocyte phenotype was assessed, and perforin expression was analyzed by flow cytometry in CD3+CD56+ T cells and NK cells. Granzyme synthesis was also evaluated in 11 of the 18 patients and compared with that of 11 age‐ and sex‐matched controls.Results: The mean number of white blood cells and lymphocytes was not different between the controls and alcoholic patients, whereas the mean number of NK cells was significantly decreased in alcoholic patients (110 ± 79/mm3 versus 271 ± 192/mm3; p < 0.03). Perforin expression in T CD3+/CD56+ and in NK cells was significantly decreased in alcoholic patients compared with controls: 16 ± 3% vs. 36 ± 4% (p < 0.03) and 65 ± 15% vs. 78 ± 9% (p= 0.04), respectively. The percentage of cells expressing granzyme was similar in both groups.Conclusions: A decrease in perforin expression by cytotoxic cells could be a major factor in explaining the physiopathologic mechanisms of several alcohol‐associated diseases.
I. Veterans Affairs Cooperative Study of Polyenylphosphatidylcholine in Alcoholic Liver Disease: Effects on Drinking Behavior by Nurse/Physician Teams
Authors: Lieber Charles S. , Weiss David G. , Groszmann Roberto , Paronetto Fiorenzo , Schenker Steven ,   for the Veterans Affairs Cooperative Study 391 Group
Published: November 2003

Background: This multicenter prospective, randomized, double‐blind placebo‐controlled trial was designed to evaluate the effectiveness of polyenylphosphatidylcholine against the progression of liver fibrosis toward cirrhosis in alcoholics. Seven hundred eighty‐nine alcoholics with an average intake of 16 drinks per day were enrolled. To control excessive drinking, patients were referred to a standard 12‐step–based alcoholism treatment program, but most patients refused to attend. Accordingly, study follow‐up procedures incorporated the essential features of the brief‐intervention approach. An overall substantial and sustained reduction in drinking was observed. Hepatic histological and other findings are described in a companion article.Methods: Patients were randomized to receive daily three tablets of either polyenylphosphatidylcholine or placebo. Monthly follow‐up visits included an extensive session with a medical nurse along with brief visits with a study physician (hepatologist or gastroenterologist). A detailed physical examination occurred every 6 months. In addition, telephone consultations with the nurse were readily available. All patients had a liver biopsy before entry; a repeat biopsy was scheduled at 24 and 48 months.Results: There was a striking decrease in average daily alcohol intake to approximately 2.5 drinks per day. This was sustained over the course of the trial, lasting from 2 to 6 years. The effect was similar both in early dropouts and long‐term patients, i.e., those with a 24‐month biopsy or beyond.Conclusions: In a treatment trial of alcoholic liver fibrosis, a striking reduction in alcohol consumption from 16 to 2.5 daily drinks was achieved with a brief‐intervention approach, which consisted of a relative economy of therapeutic efforts that relied mainly on treatment sessions with a medical nurse accompanied by shorter reinforcing visits with a physician. This approach deserves generalization to address the heavy drinking problems commonly encountered in primary care and medical specialty practices.
The Effects of Moderate Ethanol Consumption on the Liver of the Monkey, Macaca fascicularis
Authors: Ivester Priscilla , Shively Carol A. , Register Thomas C. , Grant Kathleen A. , Reboussin David M. , Cunningham Carol C. 
Published: November 2003

Background: Although evidence has accumulated for the cardioprotective effects of moderate ethanol consumption, little is known about the effects on the liver of consuming the equivalent of two drinks per day. The objective of this study was to determine the effects of moderate ethanol administration on the hepatic content of enzymes involved in ethanol oxidation, on hepatic lipid accumulation, and on serum markers of liver function/damage in the monkey, Macaca fascicularis.Methods: Ovariectomized, adult monkeys were maintained for 34 months on an atherogenic diet containing cholesterol 1.21 mg/kJ. They were trained to drink ethanol plus vehicle at a dose of 0.5 g/kg body weight, which was administered 5 days a week for 2 years. Blood was collected for ethanol concentrations (1 hr after ethanol administration) and was also assayed for γ‐glutamyltransferase, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. Liver obtained at necropsy was analyzed for triglyceride and cholesterol contents and for alcohol dehydrogenase, cytochrome P450 2E1, and cytochrome P450 3A4 by Western blots.Results: The blood ethanol concentrations measured 1 hr after ethanol administration were relatively constant over the 2‐year dosing period. Hepatic levels of alcohol dehydrogenase and the cytochrome P450s were not significantly different between ethanol‐consuming animals and control animals. Ethanol‐associated increases in liver triglyceride were not significant due to high variability in hepatic lipid content in both the controls and ethanol consumers. However, covariance analyses using pretreatment concentrations of plasma cholesterol and apolipoprotein A‐I suggested that the ethanol‐related increase in hepatic free cholesterol was significant. Relative to controls, alcohol consumers had higher levels of serum ALT and a transient increase in ALP at 5 months.Conclusions: The observations made in this study on primates administered an atherogenic diet suggest that moderate ethanol ingestion has modest effects on the liver, including slightly increased ALT and ALP values. However, additional studies will be required to verify that this level of consumption is hepatotoxic when ingested over extended periods. This is still a concern because some human studies suggest that levels of ethanol considered to be cardioprotective cause liver injury when consumed over a lifetime.
Demographic Characteristics of Hospitalized Patients With Alcoholic Liver Disease and Pancreatitis in Los Angeles County
Authors: Tao Nico , Sussman Steve , Nieto Jose , Tsukamoto Hidekazu , Yuan Jian‐Min 
Published: November 2003

Background: This study sought to identify demographic characteristics of hospitalized patients with alcoholic liver disease (ALD) in Los Angeles County for the purpose of implementing new preventive and educational programs. Another specific aim of the study was to characterize demographic and comorbid differences between patients with ALD and patients with pancreatitis, another alcohol‐related disease.Methods: Analyses were performed on discharge data from all nonfederal short‐stay hospitals within Los Angeles County, released for the year 1999 by the Office of Statewide Health Planning and Development. Repeated hospital stays for ALD by the same patients were deleted from the data analysis based on individual identification numbers. For the analysis of medical costs of ALD, repeated hospital stays were included.Results: Primary diagnosis of ALD accounted for 1.2% of total deaths among hospitalized patients and was the eighth most common cause of death among diseases examined. Moreover, the fatality rate of primary ALD among ALD hospital visits was the second highest, behind septicemia. ALD was most prevalent in the middle‐aged (45–65 years old) and low‐ to middle‐income men. The age‐standardized hospitalization rate of ALD was highest in Hispanic men (61.1 per 100,000 per year), whereas that of chronic pancreatitis, another common complication of alcohol abuse, was most prevalent in African American men.Conclusions: Middle‐aged Hispanic men with low‐ to middle‐income status were identified as a high‐risk group for ALD in Los Angeles County. These data will guide us to develop a new strategy for future preventative and educational programs for ALD.
The Causal Attribution of Injury to Alcohol Consumption: A Cross‐National Meta‐Analysis From the Emergency Room Collaborative Alcohol Analysis Project
Authors: Cherpitel Cheryl J. , Ye Yu , Bond Jason , Borges Guilherme 
Published: November 2003

Background: Whereas a substantial literature exists documenting the association of alcohol and injuries, causal associations are less well established.Methods: The relationship of drinking‐in‐the‐event variables with attributing a causal association of alcohol consumption and the injury event was examined by using meta‐analysis across 13 emergency room studies from 8 countries included in the Emergency Room Collaborative Alcohol Analysis Project.Results: Pooled odds ratios for both log‐transformed blood alcohol concentration at the time of the emergency room visit and the amount of alcohol consumed in the 6 hr before injury were positively predictive (1.19 and 1.80, respectively) and heterogeneous across studies. Effect size changed little when age and gender were controlled. When stratifying on reporting five or more drinks on an occasion during the last year (5+ yearly drinkers), the amount consumed was positively predictive of reporting a casual association of drinking and injury only for 5+ yearly drinkers. The effect size of feeling drunk at the time of injury, controlling for the amount of alcohol consumed, was positively predictive (2.04) but heterogeneous across studies. Meta‐analysis regression found the level to which alcohol is consumed in a detrimental pattern to be a significant predictor of blood alcohol concentration, and of the amount consumed and feeling drunk at the time of injury, on causal attribution, with a lower detrimental pattern level with a larger effect size.Conclusions: The association of acute use of alcohol on causal attribution may be affected by chronic use to some extent, but this association is negatively affected by the degree to which a society exhibits harmful drinking patterns.
The Prevalence of DSM‐III‐R Alcohol Dependence in Two American Indian Populations
Authors: Spicer Paul , Beals Janette , Croy Calvin D. , Mitchell Christina M. , Novins Douglas K. , Moore Laurie , Manson Spero M. ,   the American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project Team
Published: November 2003

Background: Evidence suggests that American Indian (AI) populations may be at increased risk for problems with alcohol, but a lack of community‐based research using diagnostic criteria has constrained our ability to draw inferences about the extent of severe alcohol problems, such as dependence, in AI populations.Methods: This article draws on data collected by the American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI‐SUPERPFP), which involved interviews with 3084 AI people living on or near their reservations. The AI‐SUPERPFP sample was drawn from two culturally distinct tribes, which were designated with geographical descriptions: Northern Plains (NP) and Southwest (SW). Comparisons with data collected by the National Comorbidity Survey (NCS) were explored by using shared measures to situate the findings from AI‐SUPERPFP in a national context.Results: Lifetime rates of DSM‐III‐R alcohol dependence for men in both AI‐SUPERPFP samples were 50% higher than those found in the NCS. Rates of lifetime alcohol dependence for women varied by sample, however; NP women had twice the rate of women in the NCS, but SW women had rates quite similar to those of NCS women. Patterns for 12‐month alcohol dependence in AI‐SUPERPFP were generally more similar to those found in NCS.Conclusions: The rates of DSM‐III‐R alcohol dependence found in AI‐SUPERPFP were generally higher than US averages and justify continued attention and concern to alcohol problems in AI communities, but they are not nearly as high as those in other reports in the literature that rely on less stringent sampling methods. Furthermore, significant sociocultural influences on the correlates of alcohol dependence in AI communities are evident in these data, underscoring the need to appreciate the complex and varying influences on the patterning of alcohol problems in the diverse cultural contexts of the US.