bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secular Trends in the Familial Transmission of Alcoholism
Authors: Reich Theodore , Cloninger C. Robert , Van Eerdewegh Paul , Rice John P. , Mullaney Joseph 
Published: April 2006

This is a study of the familial transmission of alcoholism in the families of 60 female and 240 male alcoholics ascertained in four psychiatric hospital units and in a local parole office. Eight hundred and thirty‐one interviewed first‐degree relatives and 125 spouses are included. The lifetime population prevalences of alcoholism in white males and females based on the Epidemiological Catchment Area Study in St. Louis were compared with the family rates. A semistructured comprehensive interview schedule (Home Environment and Lifetime Psychiatric Evaluation Record) was used and diagnoses made according to Feighner criteria for alcoholism.The methods of Survival Analysis established the presence of strong secular trends in the age‐of‐onset and lifetime prevalence of alcoholism in these families and in the general population. Accordingly, new methods for the analysis of family data that incorporate secular variation were developed.The Multifactorial Model of Disease Transmission was used to estimate familial correlations and these were parameterized by the “Tau” model of Familial Transmission. The model does not assume that all familial resemblance is due to genetic factors, but also includes the possibility of nongenetic transmission. Our analyses confirmed that more recently born cohorts of individuals had increased expected lifetime prevalences of alcoholism and decreased ages of onset, when compared with older cohorts. Separate age‐of‐onset distributions were required for males and females and the secular trends in age‐of‐onset were greatest in females. The differences between males and females were least in more recently born cohorts suggesting that sex‐specific differences in the family and population distribution of alcoholism are decreasing.Sex and cohort specific transmissibilities for alcoholism were found and the age‐specific transmissibilities in females (t2= 0.27–0.59) were significantly less than that for males (t2= 0.65–0.98). The transmissibilities were greatest in the youngest cohorts. The correlation between nonfamilial environmental factors common to siblings was 0.22 and a large degree of assortative mating was present (Rm=0.64).The influence of parental transmissible factors was greater than that expected for polygenic transmission, strongly suggesting the presence of intrafamilial nongenetic familial transmission between generations.
Ethanol‐induced Changes in Morphology and Strength of Femurs of Rats
Authors: Peng Tai‐Chan , Kusy Robert P. , Hirsch Philip F. , Hagaman John R. 
Published: April 2006

Chronic ingestion of ethanol resulted in ultrastructural and mechanical changes in rat femurs. Scanning electron microscopy of the distal end of the femur revealed that the trabeculae of bones from ethanol‐fed rats were thinner, more columnar, and more extensive than those from control rats. Three‐point bending tests of the rat femurs showed that the maximum force or so‐called “strength” required to break the bone was less in ethanol‐ than in control‐fed animals. A significant inverse correlation was observed between the strength required to break the femur and the dose of ethanol calculated on a body weight basis.For the first time our study presents quantitative proof that a relationship exists between bone strength and the consumption of ethanol in rats. The study revealed that ethanol consumption resulted in a weaker femur compared to controls. We suggest that a common mechanism may be responsible for the decreased bone strength of ethanol‐fed rats and the increased incidence of fractures in human alcoholics.
Influence of Ethanol on Stiffness, Toughness, and Ductility of Femurs of Rats
Authors: Kusy Robert P. , Hirsch Philip F. , Peng Tai‐Chan 
Published: April 2006

Recently, we reported that the ingestion of alcohol in rats reduced the mechanical strength of femurs. Our results showed that, as the dose exceeded 0.012 g of ethanol per gram of body weight, a significant (p<0.001) loss of “strength” occurred that was independent of sex according to the relationship
image
In the present effort, the same flexure tests were reevaluated to include the parameters of stiffness, toughness, and ductility. These latest results confirm that the femurs of rats fed an ethanol liquid diet for 4 weeks are not only weaker but also more compliant and less energy absorbing. Although the femurs of rats fed ethanol are more ductile, the bones are more prone to fracture in fatigue and impact circumstances as well as under simple loading situations. The rat may be an appropriate model to study the mechanisms that lead to the higher incidence of fractures in the alcoholic human.
In Vivo Effect of Chronic Ethanol Abuse on Membrane αl‐Glycoprotein of Lymphocytes and Immune Response to Various Stimulating Agents
Authors: Stefanini G. F. , Mazzetti M. , Zunarelli P. , Piccinini G. , Amorati P. , Capelli S. , Cicognani G. , Gasbarrini G. 
Published: April 2006

Data on the immune status of chronic alcoholic patients are rather conflicting probably due to the interference of liver disease and/or malnutrition on immune function. In order to avoid this kind of interference, peripheral lymphocytes from 12 chronic alcoholic patients in good nutritional status and without heavy liver damage and 15 healthy controls were examined in this study. Lymphocyte functional activity was evaluated by means of response to phytohemagglutinin, calcium ionophore A 23187, and autologous non‐T‐cells [autologous mixed lymphocyte reaction (AMLR)]. Phenotypical analysis was carried out by the indirect immunofluorescence technique using monoclonal antibodies specific to CD5 (mature T‐lymphocytes). CD4 (helper/inducer T‐lymphocytes), CD8 (suppressor/cytotoxic T‐lymphocytes), glycoproteins, and an immunoglobulin fraction from rabbit directed to membrane α1 acid glycoprotein (AGP) that is involved in T‐cell activation process.Our results show significant impairment in AMLR while response to phytohemagglutinin, heterologous non‐T‐cells and carcinoma ionophore did not differ from controls. No differences were present in circulating T‐lymphocytes expressing CD5, CD4, and CD8 on their membrane, whereas AGP‐bearing lymphocytes were significantly lower in chronic alcoholics (14.4 ± 8.6) than in controls (31.9 ± 8.1; p < 0.001). These results support the hypothesis of a direct action of alcohol on one of the pathways of lymphocyte activation and the role of the lymphocyte membrane AGP on the AMLR.
Are Special Treatment Facilities for Female Alcoholics Needed? A Controlled 2‐Year Follow‐up Study from a Specialized Female Unit (EWA) Versus a Mixed Male/Female Treatment Facility
Authors: Dahlgren Lena , Willander Anders 
Published: April 2006

Women with alcohol problems constitute an increasing number of patients in medical service. Do they need special care? How should the treatment program be designed?The specialized female Karolinska Project for Early Treatment of Women with Alcohol Addiction (EWA) unit at the Karolinska Hospital in Stockholm, Sweden, was opened in 1981. The aim of the project is to reach women in an early stage of alcohol dependence behavior and to develop treatment programs specific to the needs of females alone.In order to investigate the value of such a specialized female unit a controlled 2‐year follow‐up study was carried out including 200 women. The probands were treated in the female only EWA‐unit, whereas the controls were placed in the care of traditional mixed‐sex alcoholism treatment centers.The 2‐year follow‐up study showed a more successful rehabilitation regarding alcohol consumption and social adjustment for the women treated in the specialized female unit (EWA). Improvement was noted also for the controls but to a lesser extent. Probably one of the most important achievements of a specialized female unit, such as EWA, is to attract women to come for help earlier.
Effect of Alcohol on Blood Dolichol Concentration
Authors: Roine Risto P. , Nykänen Irma , Ylikahri Reino , Heikkilä Juha , Suokas Antti , Salaspuro Mikko 
Published: April 2006

Serum dolichol levels were studied in 95 active alcoholics and 16 abstinent alcoholics (at the time of blood sampling) and compared to those of 41 social drinkers. Active alcoholics had a significantly higher mean serum dolichol concentration (182.7 ± 5.1 ng/ml, p < 0.001 than either abstinent alcoholics (138.7 ± 5.4 ng/ml) or social drinkers (142.1 ± 4.1 ng/ml). During weekend (48 hr) heavy drinking (5.5 g of alcohol per kg b.w.) no significant changes were seen in mean serum dolichol concentrations in 10 healthy, nonalcoholic volunteers. Neither did moderate drinking for 10 days (60 g of alcohol daily)—preceded and followed by a period of abstinence—produce any significant changes in serum dolichol levels in 10 nonalcoholic subjects.During detoxification treatment of 12 alcoholics, mean serum dolichol concentration stayed constant for the first 7 days; on entering treatment it was 227.7 ± 15.0 ng/ml, on the 3rd day 238.5 ± 15.9 ng/ml, and on the 7th day of treatment 222.6 ± 18.6 ng/ml.Our results show that as well as increasing urinary dolichol excretion, chronic alcohol abuse also produces increased serum dolichol concentrations. However, contrary to urinary dolichols, serum dolichol levels do not react significantly to heavy drinking lasting for 48 hr in nonalcoholic volunteers. Furthermore in alcoholics increased serum dolichol concentrations do not decrease as rapidly during abstinence as urinary dolichol concentrations do.
Human Neutrophils Are Not Severely Injured in Conditions Mimicking Social Drinking
Authors: Corberand J. X. , Laharrague P. F. , Fillola G. 
Published: April 2006

In an attempt to assess the effect of alcohol per se on human polymorphonuclear neutrophils (PMN), irrespective of other physiopathological parameters, we examined neutrophil function in healthy volunteers who had taken a single large dose of whisky. Before and at different times after ingestion, several PMN properties were simultaneously tested including random migration, in vitro chemotaxis, adherence, aggregation, cytochrome C reduction, phagocytosis, bacterial killing, intracellular CAMP and cGMP contents, myeloperoxidase, and neutrophil alkaline phosphatase scores. Only phagocytosis of Staphylococcus aureus was significantly depressed after alcohol ingestion. Adherence was inhibited only in some individuals when their respective blood alcohol levels were the highest. Both alterations were moderate and reversible.These data point out the limited effect of occasional alcohol consumption on the different facets of neutrophil behavior. These findings suggest that factors other than alcohol itself could be concerned in the marked PMN dysfunction well established in chronic alcoholism.
A Comparison of Ethanol Partitioning in Biological and Model Membranes: Nonideal Partitioning is Enhanced in Synaptosomal Membranes
Authors: Sarasua Martha M. , Faught Karla R. , Steedman Susan L. , Gordin M. Daniel , Washington M. K. 
Published: April 2006

The partitioning of ethanol into mouse brain synaptosomes at 37°C was characterized as a function of ethanol concentration. In addition, the partitioning of ethanol into multilamellar dipalmitoylphosphatidylcholine (DPPC) vesicles was characterized as a function of ethanol concentration and temperature. DPPC liposomes provided a model for ethanol partitioning into a phospholipid bilayer of defined composition allowing comparison to the more complex synaptosomal membrane.The values of the partition coefficients for ethanol depend on the convention used to express concentration in the partition coefficient ratio. We express these concentrations as mole fractions of ethanol in the membrane and aqueous phases.Ethanol partitioning is nonideal (ethanol membrane: buffer partition coefficients vary with total ethanol concentration). In synaptosomes, the partition coeffients vary markedly with concentration and asymptotically approach zero at higher concentrations. In the DPPC system, the variation of the partition coefficient is less pronounced, but significant. The ethanol: DPPC partition coefficients decrease by a factor of 2 at ethanol concentrations above 3.2 × 10‐3 M. This suggests a model involving at least two distinguishable types of interactions of ethanol with the membrane. Ethanol appears to undergo both bulk phase partitioning into the membrane bilayer core and nonspecific binding to the membrane surface. In pure DPPC, bulk phase hydrophobic partitioning predominates. In synaptosomes, nonspecific surface binding appears to be a major interaction.Temperature studies indicate ethanol partitioning into DPPC increases above the phospholipid gel to liquid crystalline phase transition temperature. This suggests a preferred partitioning of ethanol into fluid state lipid. However, significant membrane concentrations of ethanol are found in gel state DPPC.
Investigations of the Role of Protein Kinase C in the Acute Sedative Effects of Ethanol
Authors: Deitrich Richard A. , Bludeau Pequita A. , Baker Rodney C. 
Published: April 2006

The activity of protein kinase C (PKC) in whole brain and brain areas of mice selectively bred for resistance (short sleep, SS) or sensitivity (long sleep, LS) to the acute ataxic effect of ethanol has been investigated. The cytosolic and membrane fractions of whole brain PKC activities are significantly less in LS mice than in SS mice. There are significant differences in PKC activity between brain areas in both the SS and LS lines. Ethanol given in ataxic doses results in significantly increased amounts in PKC activity in whole brain cytosolic fractions and in some brain areas but egually in both SS and LS mice. Ethanol added in vitro reduced enzyme activity slightly in SS brain membranes, suggesting that the mechanism of the increase in PKC activity seen after in vivo administration is indirect. These results indicate that PKC is not involved in the mechanism whereby LS and SS mice differ in alcohol sensitivity.Direct intracerebroventricular (ICV) injection of phorbol myristate acetate (PMA), an activator of PKC, resulted in increased sleep times in both SS and LS mice. ICV injection of PMA also caused a more marked decrease in body temperature in LS than in SS mice. The half‐life of PMA in brain was determined to be 9.6 hr and no metabolites could be detected.At limiting calcium concentrations, PMA added in vitro activated PKC equally well in both lines. However, PMA given ICV did not alter the level of PKC as determined in vitro.Administration of phorbol myristate‐acetate intraperitoneally (i.p.) to LS mice increased their sleep time response to ethanol and caused a prolonged depression of temperature when given alone. Similar treatment of SS mice caused no change or a decreased sleep time and a smaller temperature drop as compared to LS mice. There was no effect of i.p.‐administered PMA or PMA plus ethanol on PKC activity in whole brain cytosol or membrane fraction except for a decreased activity in membranes of SS mice given PMA alone. It was found that only small amounts of PMA given i.p. reached the brain. There appears to be different mechanisms by which phorbol esters alter sleep time in these mice, one via a central effect which is not related to why LS and SS mice differ and one via a peripherial effect that may be related to the SS and LS differences.
Combined Upper and Lower Gastrointestinal Endoscopy: A Prospective Study in Alcoholic and Nonalcoholic Cirrhosis
Authors: Rabinovitz Mordechai , Kumar Shashi , Kajani Mirza , Van Thiel David H. , Gavaler Judith S. 
Published: April 2006

Upper gastrointestinal hemorrhage is one of the more important complications of cirrhosis. Most of the available data regarding the prevalence of upper and lower gastrointestinal sites of bleeding in cirrhotic patients have been obtained in individuals with alcoholic cirrhosis evaluated in the course of an acute gastrointestinal bleeding episode. Few data exist, however, as to the prevalence of either potential bleeding sites or of normal endoscopic findings in hemo‐dynamically stable individuals with cirrhosis of any etiology.Five hundred ten cirrhotic subjects, who were evaluated for possible liver transplantation (OLTx) between January 1985 and June 1987, were included in this study. Seventy‐five had alcoholic cirrhosis and 435 had nonalcoholic cirrhosis of various etiologies. Of these 510 patients, 412 underwent combined upper and lower gastrointestinal endoscopy and 98 underwent upper gastrointestinal endoscopy alone.Gastritis, gastric and duodenal ulcer disease were found significantly (each at least p < 0.025) more often in patients with alcoholic liver disease than in those with nonalcoholic liver disease. The prevalence of the various lower gastrointestinal lesions in both groups was similar. Of particular interest is the fact that in alcoholic cirrhotics, the prevalence of gastritis, gastric ulcer and duodenal ulcer disease was unrelated to the degree of portal hypertension, whereas in the nonalcoholic cirrhotics the prevalence of gastritis and duodenal ulcer disease but not gastric ulcer disease was associated significantly with the degree of portal hypertension as assessed by the presence or absence of large esophageal varices, ascites, and hepatic encephalopathy.
Immunotoxicity of Alcohol in Young and Old Mice. I. In vitro Suppressive Effects of Ethanol on the Activities of T and B Immune Cells of Aging Mice
Authors: Chang M‐P. , Norman D. C. , Makinodan T. 
Published: April 2006

A murine aging model was employed to assess effects of ethanol exposure on the T‐cell proliferative response to mitogenic stimulation and on the T cell‐dependent primary antibody response to sheep red blood cells (RBC) in vitro. Splenic cells from young (3–5 months) and old (28–32 months) BALB/c mice were first assessed for their ability to produce interleukin (IL) 2 and proliferate in response to mitogenic stimulation in the presence of various doses of ethanol. Then, splenic T blast cells from young and old mice, generated by Con A‐activation, were assessed for their IL2‐dependent proliferative capacity in the presence of various doses of ethanol. Finally, splenic cells of young and old mice were assessed for their ability to generate plaque‐forming cells (PFC) in response to sheep RBC in the presence of various doses of ethanol.The results revealed that ethanol has a much greater suppressive effect on old than young splenic T cells (10–15 times), as judged by their ability to proliferate in response to mitogenic stimulation. However, the magnitude of the difference in the suppressive effect is less when the cells are cycling (2 times). Furthermore, ethanol had only a minimal suppressive effect on IL2 production by T cells of both young and old mice, even at the concentration of 100 mm. These findings would suggest that the ethanol‐mediated suppression of T cell proliferation of both young and old mice is more likely due to an impairment of metabolic event(s) associated with or subsequent to the interaction of IL2 and IL2 receptor leading to cellular replication. The primary anti‐sheep RBC antibody responses of young and old spleen cells were also significantly suppressed, but the magnitude of suppression was comparable.
Plasma Noradrenaline, Platelet α2‐Adrenoceptors, and Functional Scores during Ethanol Withdrawal
Authors: Smith A. J. , Brent P. J. , Henry D. A. , Foy A. 
Published: April 2006

Plasma noradrenaline and platelet α2‐adrenoceptor density (sites/cell using 3H‐rauwolscine with and without phentolamine) were correlated with withdrawal score in 23 hospitalized patients undergoing ethanol withdrawal. Control groups for plasma noradrenaline were 25 patients admitted to hospital for elective gastroscopy and 12 laboratory workers accustomed to venipuncture. Controls for platelet α2‐adrenoceptor measurements were a separate group of 31 normal subjects with a mean age close to that of the patients' withdrawing from ethanol.Plasma noradrenaline was significantly higher in the patients undergoing ethanol withdrawal than in patients admitted to hospital for elective endoscopy. Twelve laboratory controls had plasma noradrenaline levels significantly lower than either patient group.A significant though poor statistical correlation existed between ethanol withdrawal score and simultaneously determined plasma noradrenaline level.Platelet α2‐adrenoceptor sites/cell were reduced in ethanol withdrawal compared with the normal controls. Platelet α2‐adrenoceptor sites/cell increased over the first 24 hr of ethanol withdrawal but remained significantly lower than control values. The change in platelet adrenoceptors was accompanied by a fall in mean plasma noradrenaline.Thus, the stress of hospital admission itself is associated with an increase in plasma noradrenaline, but ethanol withdrawal enhances this increase, which is accompanied by and probably causes a reduction in platelet α2‐adrenoceptor numbers. These changes begin to return towards normal within 24 hr as the withdrawal reaction subsides.
Ethanol Causes Accelerated G1 Arrest in Differentiating HL‐60 Cells
Authors: Cook Robert T. , Keiner Judith A. , Yen Andrew 
Published: April 2006

The effects of clinically relevant ethanol concentrations on myeloid differentiation in the HL‐60 cell promyelocytic leukemia line have been studied. The exposure of noninduced stem cells to 60 mm ethanol results in an increase in G1 cells, but there is no increase in superoxide production or expression of the Mo1 antigen. When HL‐60 cells are induced to differentiate along the myeloid line with dimethylsulfoxide (DMSO) or retinoic acid (RA), there is a shift to smaller cell size, an increase in G1 cells and acquisition of the ability to produce superoxide as reported previously by several authors. When ethanol is present during differentiation, there are further increases in G1 cells, and increases in the percentage of cells which produce superoxide and express Mo1, and decreases in mean cell size and total growth during the incubation period. Regrowth experiments after periods of differentiation indicate that the increased G1 arrest seen in the presence of ethanol represents terminal commitment if inducer is present, but in the absence of inducer the increased G1 percentage is readily reversible.Examination of RNA content by flow cytometry reveals a decrease in both the peak and mean G1 RNA content during DMSO or RA induced differentiation. These decreases are accentuated by the presence of ethanol, resulting in a higher G1A/G1B ratio than in nonexposed cells.These findings indicate that ethanol enhances G1 growth arrest in HL‐60 cells exposed to myeloid inducers. Partial differentiation occurs during this process, resulting in terminally arrested cells, some of which have undergone fewer postinduction cell divisions than normal and may not be fully competent.