bluuebunny/crossref_metadata_2025 huggingface dataset:
Bile Reflux into the Stomach and the Esophagus for Volunteers Older than 40 Years
Authors: Bollschweiler Elfriede , Wolfgarten Eva , Pütz Benito , Gutschow Christian , Hölscher Arnulf H.
Published: March 2005

Background: An increased incidence of Barrett’s esophagus in cases with combined acidic and bile reflux is reported. The volunteers serving as controls in those studies were significantly younger than the patients. The aim of this study was to analyze bile reflux patterns of healthy volunteers aged comparably to patients with Barrett’s esophagus. Subjects and Methods: 19 older (8 f, 11 m; median age 51 years) (OV) and 20 younger (10 f, 10 m; median age 25 years) (YV) healthy volunteers without history of gastrointestinal disease or medication underwent simultaneous 24-hour pH and bile monitoring (Bilitec®). All subjects consumed a special diet that did not interfere with bile measurements. Indicators for bile reflux in the stomach and esophagus: bilirubin probe absorption >0.25 in total measuring period (TM), upright position (excluding postprandial periods) (UP) and supine period (SP). Results: There were no differences between older and younger volunteers in pH monitoring. Comparing the periods of bilirubin exposure of the stomach, the median (lower and upper quartile) percentage of time was OV = 5.7% (1.0–15.0%) and YV = 3.5% (0.1–7.8%) respectively for TM (n.s.), OV = 3.1% (0.7–9.4%) and YV = 0.4% (0.0–7.1%) for UP (n.s.), and OV = 2.1% (0.2–16.7%) and YV = 5.9% (0.0–12.2%) respectively for SP (n.s.). In 10/19 older volunteers and in 18/20 younger volunteers, no reflux of bile into the esophagus was measured. However, 4 older volunteers presented bile reflux from 4.6 to 51% of the total measuring period in contrast to the younger group with a maximum of 1.3% of TM. Conclusion: No significant differences in bile reflux into the stomach were distinguishable between younger and older healthy volunteers, but older volunteers more frequently exhibited bile reflux into the esophagus.
Altered Expression of TGF-β Receptors in Hepatocellular Carcinoma – Effects of a Constitutively Active TGF-β Type I Receptor Mutant
Authors: Musch Annemarie , Rabe Christian , Paik Mignon-Denise , Berna Marc Jean , Schmitz Volker , Hoffmann Per , Nischalke Hans Dieter , Sauerbruch Tilman , Caselmann Wolfgang H.
Published: March 2005

Background/Aims: Hepatocellular carcinomas (HCC) often show resistance to the effects of transforming growth factor-β (TGF-β). This study focuses on molecular mechanisms of this resistance to explore ways to overcome it. Methods: Transcription and protein expression of TGF-β type I and type II receptors (TGF-βRI/RII) were analyzed in clinical HCCs and the human hepatoma cell lines HuH-7 and HepG2. HuH-7 cells were transiently and stably transfected with a constitutively active TGF-βRI mutant (CA TGF-βRI). Resulting growth kinetics, integrin expression, invasiveness, TGF-β-mediated activation of human plasminogen activator inhibitor type-1 (PAI-1) promoter and Smad expression were determined. Results: In clinical HCCs, there was less TGF-βRII (6/10 cases) and more TGF-βRI (8/10 cases) protein expression detectable in tumor compared to adjacent liver tissue. In HuH-7 cells, TGF-βRII expression was likewise decreased. Cells transiently transfected with CA TGF-βRI exhibited strong TGF-β-related PAI-1 promoter activation. Stably transfected cells showed an attenuated response of the PAI-1 promoter, but increased Smad7 expression. Proliferation of stable clones was decreased. There was no change in integrin expression or invasiveness. Conclusions: Decreased TGF-βRII protein expression might cause TGF-β resistance in a subset of clinical HCCs. Stable transfection with CA TGF-βRI reverses this in HuH-7 cells without increasing invasiveness.
High Prevalence of Celiac Disease in Patients with Lactose Intolerance
Authors: Ojetti Veronica , Nucera Gabriella , Migneco Alessio , Gabrielli Maurizio , Lauritano Cristiano , Danese Silvio , Assunta Zocco Maria , Nista Enrico Celestino , Cammarota Giovanni , de Lorenzo Antonino , Gasbarrini Giovanni , Gasbarrini Antonio
Published: March 2005

Background/Aims: Acquired lactase deficiency is a common cause of gastrointestinal symptoms but its etiology remains unclear. Celiac disease could lead to lactase deficiency and is much more common than previously suspected. Several studies have highlighted the prevalence of lactose intolerance in celiac disease, but studies assessing the prevalence of celiac disease in lactose intolerance are lacking. We evaluated the prevalence of celiac disease in patients with a positive H2-lactose breath test compared to a control group. Methods: This retrospective study included 54 patients (15 males/39 females; mean age 37.8 ± 7 years) from southern Italy, referred to the Gastroenterology Unit for bloating and diarrhea after the introduction of milk or dietary lactose. They had a positive H2-lactose breath test and a negative H2-glucose breath test. 50 blood donors were drawn from a similar population, matched for sex and age, and enrolled as a control group. All patients were screened for possible celiac disease by measuring the serum level of IgA antibodies to endomysium, anti-transglutaminase and total IgA. Patients positive for at least one of these markers were submitted to upper gastrointestinal endoscopy. Results: None of the patients had a IgA deficiency. 24% of the patients showed positivity of celiac disease antibodies compared to 2% in the control group (p < 0.001). Histologic samples of these patients showed villous atrophy (53.8% Marsh type IIIa, 38.4% Marsh IIIb, and 7.6% with Marsh type IIIc) confirming the celiac disease, while in the control subjects duodenal biopsies were normal. Conclusions: A high prevalence of celiac disease was observed in patients with a positive H2-lactose breath test compared to healthy controls. In these subjects lactase deficiency seems to be the only manifestation of celiac disease. We suggest serologic screening for celiac disease in all patients with a positive H2-lactose breath test before beginning a milk-exclusion diet.
Regulatory Roles of Galectins in the Immune Response
Authors: Liu Fu-Tong
Published: March 2005

Galectins are a family of animal lectins with affinity for β-galactosides. They are differentially expressed by various immune cells and their expression levels appear to be dependent on cell differentiation and activation. They can interact with cell-surface and extracellular matrix glycoconjugates (glycoproteins and glycolipids), through lectin-carbohydrate interactions. Through this action, they can promote cell growth, affect cell survival, modulate cell adhesions, and induce cell migration. They appear to do so by binding to different glycoconjugates decorated by suitable saccharides, rather than through specific receptors. Galectins do not have a classical signal peptide and are often localized in intracellular compartments, including the nucleus. Intracellularly, they can regulate cell growth and survival by interacting with cytoplasmic and nuclear proteins, through protein-protein interactions, thereby affecting intracellular signaling pathways. Current research indicates that galectins play important roles in the immune response through regulating the homeostasis and functions of the immune cells.
Presymptomatic Signs in Healthy CJD Mutation Carriers
Authors: Gigi Ariela , Vakil Eli , Kahana Ester , Hadar Uri
Published: March 2005

Creutzfeldt-Jacob disease (CJD) is a rapidly progressing dementia with neurological, psychiatric and cognitive symptoms. We focused our study on the familial CJD form among Libyan Jews (the E200K mutation), trying to identify preclinical neuropsychological signs in mutation carriers to facilitate early diagnosis of the disease. A wide range of neuropsychological tests was administered to 27 healthy volunteers, all first-degree relatives of genetic CJD patients. Thirteen of our participants were gene mutation carriers (E200K) and 14 controls. The healthy mutation carriers reported significantly lower Trait and higher State anxiety scores. Repeated Measure analysis showed statistical significance. The Anxiety Index (State-Trait Anxiety Score) progressed with age in the carriers’ group but not in the controls. Since this was more pronounced in the older subjects, we suggest that abnormal stress mechanisms precede the clinical onset of CJD. Cognitive differences have also been found between carriers and controls, especially in visual recognition of pictured objects. Both kinds of differences (anxiety levels and cognitive deficits) were most pronounced in elderly subjects. This study is the first to show any dysfunction in healthy CJD mutation carriers.
Ghrelin Is Suppressed by Glucagon and Does Not Mediate Glucagon-Related Growth Hormone Release
Authors: Hirsh Denton , Heinrichs Claudine , Leenders Bert , Wong Alfred C.K. , Cummings David E. , Chanoine Jean-Pierre
Published: March 2005

Background:Glucagon stimulation is routinely used as a provocative test to assess growth hormone (GH) sufficiency in pediatrics. Ghrelin also markedly stimulates GH secretion. Because glucagon stimulates the promoter of the ghrelin gene in vitro as well as ghrelin secretion by the perfused rat stomach, we sought todetermine whether ghrelin mediates glucagon-induced GH secretion. Methods: We compared ghrelin, GH, insulin and glucose responses following administration of 0.03 mg/kg intravenously (iv; max. 1 mg) and 0.1 mg/kg intramuscularly (im; max. 2 mg) of glucagon in two groups (n = 10–11/group) of GH-sufficient children. We also measured ghrelin before and 6 min after iv administration of 1 mg glucagon in 21 adult subjects. Results: In children, glucagon caused a 26% decrease in ghrelin and a 72% increase in glucose concentrations that were independent of the dose or administration route of glucagon. In contrast, the insulin response was 2–3 times higher following administration of 0.1 mg/kg im compared to 0.03 mg/kg of glucagon iv. There was a significant correlation between the maximum decrease in ghrelin and increases in glucose (p = 0.03) but not in insulin. There was a significant correlation between ghrelin and GH area under the curve after controlling for the dose of glucagon (p = 0.03) but not for the maximum increase in glucose.In normal adults, glucagon administration caused a 7% decrease in ghrelin concentrations after 6 min (p = 0.0002). Conclusion: Ghrelin does not play a causal role in the GH response to pharmacological glucagon administration, which suppresses ghrelin levels starting a few minutes after injection.
Syndecans
Authors: Tkachenko Eugene , Rhodes John M. , Simons Michael
Published: March 2005

Cell-associated proteoglycans provide highly complex and sophisticated systems to control interactions of extracellular cell matrix components and soluble ligands with the cell surface. Syndecans, a conserved family of heparan- and chondroitin-sulfate carrying transmembrane proteins, are emerging as central players in these interactions. Recent studies have demonstrated the essential role of syndecans in modulating cellular signaling in embryonic development, tumorigenesis, and angiogenesis. In this review, we focus on new advances in our understanding of syndecan-mediated cell signaling.
Toward Deciphering the Khipu
Authors: Brokaw Galen
Published: March 2005

Gary Urton argues that the khipu employed a seven-bit system of binary coding based upon seven inherently binary characteristics. In most cases, he provides little if any ethnographic or historical evidence for the significance of individual binary features, and his justification for the larger binary code as following from Andean concepts of dualism is theoretically unfounded. Furthermore, the theory of binary coding suffers from numerous logical inconsistencies and contradictions.
The Terrorist Endgame
Authors: de Mesquita Ethan Bueno
Published: March 2005

The author models the relationship between a government and former terrorists as a game with both moral hazard and learning. The government is uncertain about both the former terrorists’ ability and skill at providing counterterrorism aid. The government has the option—after observing the success or failure of counterterrorism—of replacing the former terrorist leadership with a new negotiating partner. This study demonstrates that the threat of replacement, in addition to promised concessions, provides incentives for former terrorists to exert counterterrorism effort, particularly when the potential replacements are of moderate ability. Furthermore, the author identifies conditions under which governments are likely to replace the former-terrorist leadership with which it has been negotiating. The model also has implications for the effect of counterterrorism successes on future concessions and the impact of the government’s ability to consider replacing the former terrorists on concessions and counterterrorism.
Mixed Logit Estimation of Radical Islamic Terrorism in Europe and North America
Authors: Barros Carlos Pestana , Proença Isabel
Published: March 2005

This article estimates what characteristics (e.g., location, number of casualties, and type of attack) are associated with an Islamic terrorist attack. This is established by identifying the significant determinants of the probability that an attack had been carried out by Islamic terrorists. For Europe, the United States, and Canada, the analysis employs ITERATE (International Terrorism: Attributes of Terrorist Events) data from October 1979 to December 2002 to ascertain the significant characteristics of Islamic terrorist attacks. A random-parameter logit model is used to analyze the probability of such attacks, taking into account the heterogeneity of the sample data. This model outperforms the standard logit model. Some policy implications are presented.
Does Democracy Promote or Reduce Transnational Terrorist Incidents?
Authors: Li Quan
Published: March 2005

This article studies the various mechanisms by which democracy affects transnational terrorism. New theoretical mechanisms are identified that either complement or encompass existing arguments. Different effects of democracy on transnational terrorism are assessed for a sample of about 119 countries from 1975 to 1997. Results show that democratic participation reduces transnational terrorist incidents in a country, while government constraints increase the number of those incidents, subsuming the effect of press freedom. The proportional representation system experiences fewer transnational terrorist incidents than either the majoritarian or the mixed system.
IDS Models of Airline Security
Authors: Heal Geoffrey , Kunreuther Howard
Published: March 2005

This article applies an earlier analysis of interdependent security issues to a general class of problems involving discrete interdependent exposure to terrorist risks. Any agent’s incentive to adopt risk-reducing measures depends on the actions of others because of the negative externalities created by not investing in protection. Using airline security as an illustrative example, the authors show that any individual airline will be less likely to invest in security measures as more firms in the industry also fail to invest. For a wide range of parameters, both individual airline and total industry profits can be significantly improved by everyone investing in security. The article discusses the role that private trade associations as well as public-sector actions such as taxes, subsidies, and regulations can play in dealing with the negative externalities caused by interdependent security. The article concludes with suggestions for future research.
Political and Militant Wings within Dissident Movements and Organizations
Authors: Siqueira Kevin
Published: March 2005

A model is developed to provide a basis for investigating the nature of faction behavior and the interrelationships between factions and between factions and their supporters under conditions of competition and cooperation. A general finding of the study illustrates the fact that when factions act competitively and independently of one another, the results do not necessarily lead to increased dissident activity and violence when compared to the case when factions act jointly and coordinate their actions. For example, when faction activities generate positive externalities and are strategic complements, competition and the independent behavior of factions lead to decreased levels of dissident activity. The model can also be used to derive implications for various types of counterterrorism policies when a government faces independently acting groups within a dissident movement.
HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL)
Authors: Soulier Jean , Clappier Emmanuelle , Cayuela Jean-Michel , Regnault Armelle , García-Peydró Marina , Dombret Hervé , Baruchel André , Toribio Maria-Luisa , Sigaux François
Published: March 2005

Using a combination of molecular cytogenetic and large-scale expression analysis in human T-cell acute lymphoblastic leukemias (T-ALLs), we identified and characterized a new recurrent chromosomal translocation, targeting the major homeobox gene cluster HOXA and the TCRB locus. Real-time quantitative polymerase chain reaction (RQ-PCR) analysis showed that the expression of the whole HOXA gene cluster was dramatically dysregulated in the HOXA-rearranged cases, and also in MLL and CALM-AF10-related T-ALL cases, strongly suggesting that HOXA genes are oncogenic in these leukemias. Inclusion of HOXA-translocated cases in a general molecular portrait of 92 T-ALLs based on large-scale expression analysis shows that this rearrangement defines a new homogeneous subgroup, which shares common biologic networks with the TLX1- and TLX3-related cases. Because T-ALLs derive from T-cell progenitors, expression profiles of the distinct T-ALL subgroups were analyzed with respect to those of normal human thymic subpopulations. Inappropriate use or perturbation of specific molecular networks involved in thymic differentiation was detected. Moreover, we found a significant association between T-ALL oncogenic subgroups and ectopic expression of a limited set of genes, including several developmental genes, namely HOXA, TLX1, TLX3, NKX3-1, SIX6, and TFAP2C. These data strongly support the view that the abnormal expression of developmental genes, including the prototypical homeobox genes HOXA, is critical in T-ALL oncogenesis.
Hemoglobin levels correlate with interleukin-6 levels in patients with advanced untreated epithelial ovarian cancer: role of inflammation in cancer-related anemia
Authors: Macciò Antonio , Madeddu Clelia , Massa Daniela , Mudu Maria C. , Lusso Maria R. , Gramignano Giulia , Serpe Roberto , Melis Gian Benedetto , Mantovani Giovanni
Published: March 2005

Anemia occurs in more than 30% of patients with epithelial ovarian cancer before any surgery. High levels of proinflammatory cytokines and increased oxidative stress may contribute to the development of cancer-related anemia. We assessed a population of previously untreated patients with advanced epithelial ovarian cancer to evaluate whether there was a correlation between hemoglobin (Hb) and parameters of inflammation and oxidative stress, stage of disease, and performance status (PS). In 91 patients with epithelial ovarian cancer and 95 healthy women matched for age, weight, and height, levels of Hb, C-reactive protein (CRP), fibrinogen (Fbg), proinflammatory cytokines, leptin, reactive oxygen species (ROS), and antioxidant enzymes were assessed at diagnosis before treatment. The correlations between Hb, parameters of inflammation and oxidative stress, stage, and PS were evaluated. Hb levels were lower in patients with advanced epithelial ovarian cancer than in control subjects and inversely related to stage and PS. Hb negatively correlated with CRP, Fbg, interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNFα), and ROS, and positively correlated with leptin and glutathione peroxidase (GPx). Multivariate regression analysis showed that stage and IL-6 were independent factors determining Hb values. This evidence suggests that anemia in epithelial ovarian cancer is common and its presence is related to stage of disease and markers of inflammation.
The MLL partial tandem duplication: evidence for recessive gain-of-function in acute myeloid leukemia identifies a novel patient subgroup for molecular-targeted therapy
Authors: Whitman Susan P. , Liu Shujun , Vukosavljevic Tamara , Rush Laura J. , Yu Li , Liu Chunhui , Klisovic Marko I. , Maharry Kati , Guimond Martin , Strout Matthew P. , Becknell Brian , Dorrance Adrienne , Klisovic Rebecca B. , Plass Christoph , Bloomfield Clara D. , Marcucci Guido , Caligiuri Michael A.
Published: March 2005

MLL (ALL-1) chimeric fusions and MLL partial tandem duplications (PTD) may have mechanistically distinct contributions to leukemogenesis. Acute myeloid leukemia (AML) blasts with the t(9;11)(p22; q23) express MLL-AF9 and MLL wild-type (WT) transcripts, while normal karyotype AML blasts with the MLLPTD/WT genotype express MLL PTD but not the MLL WT. Silencing of MLL WT in MLLPTD/WT blasts was reversed by DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, and MLL WT induction was associated with selective sensitivity to cell death. Reduction of MLL PTD expression induced MLL WT and reduced blast colony-forming units, supporting opposing functions for MLL PTD and MLL WT whereby the MLL PTD contributes to the leukemic phenotype via a recessive gain-of-function. The coincident suppression of the MLL WT allele with the expression of the MLL PTD allele, along with the functional data presented here, supports the hypothesis that loss of WT MLL function via monoallelic repression contributes to the leukemic phenotype by the remaining mutant allele. These data from primary AML and the pharmacologic reversal of MLL WT silencing associated with a favorable alteration in the threshold for apoptosis suggest that these patients with poor prognosis may benefit from demethylating or histone deacetylase inhibitor therapy, or both.
A novel firmicute protein family related to the actinobacterial resuscitation-promoting factors by non-orthologous domain displacement
Authors: Ravagnani Adriana , Finan Christopher L , Young Michael
Published: March 2005

Background

In Micrococcus luteus growth and resuscitation from starvation-induced dormancy is controlled by the production of a secreted growth factor. This autocrine r esuscitation-p romoting f actor (Rpf) is the founder member of a family of proteins found throughout and confined to the actinobacteria (high G + C Gram-positive bacteria). The aim of this work was to search for and characterise a cognate gene family in the firmicutes (low G + C Gram-positive bacteria) and obtain information about how they may control bacterial growth and resuscitation.

Results

In silico analysis of the accessory domains of the Rpf proteins permitted their classification into several subfamilies. The RpfB subfamily is related to a group of firmicute proteins of unknown function, represented by YabE of Bacillus subtilis. The actinobacterial RpfB and firmicute YabE proteins have very similar domain structures and genomic contexts, except that in YabE, the actinobacterial Rpf domain is replaced by another domain, which we have called Sps. Although totally unrelated in both sequence and secondary structure, the Rpf and Sps domains fulfil the same function. We propose that these proteins have undergone "non-orthologous domain displacement", a phenomenon akin to "non-orthologous gene displacement" that has been described previously. Proteins containing the Sps domain are widely distributed throughout the firmicutes and they too fall into a number of distinct subfamilies. Comparative analysis of the accessory domains in the Rpf and Sps proteins, together with their weak similarity to lytic transglycosylases, provide clear evidence that they are muralytic enzymes.

Conclusions

The results indicate that the firmicute Sps proteins and the actinobacterial Rpf proteins are cognate and that they control bacterial culturability via enzymatic modification of the bacterial cell envelope.
The role of the cytoskeleton in cell body enlargement, increased nuclear eccentricity and chromatolysis in axotomized spinal motor neurons
Authors: McIlwain David L , Hoke Victoria B
Published: March 2005

Background

When spinal motor axons are injured, the nucleolus, nucleus and cell body of the injured cell transiently increase in size, the nucleus becomes more eccentrically placed, and the organization of polyribosomes into Nissl bodies is temporarily disrupted. The mechanisms for these classical morphological responses to axotomy have not been satisfactorily explained.

Results

In this study we address the role of the cell body cytoskeleton in these structural changes. We show that the cytoskeleton of uninjured lumbar motor neuron cell bodies maintains nucleolar, nuclear and cell body size and nuclear position. When isolated, the relatively insoluble cell body cytoskeleton contains Nissl bodies and lipofuscin granules. After axotomy, protein labeling increases markedly and the cytoskeleton enlarges, increasing nucleolar, nuclear and cell body size, as well as nuclear eccentricity. Nearly all of the protein mass that accumulates in the cell body after axotomy appears to be added to the cytoskeleton.

Conclusion

We conclude that axotomy causes the conjugate enlargement of the nucleolus, nucleus and cell body and increases nuclear eccentricity in spinal motor neurons by adding protein to the cytoskeleton. The change in nuclear position, we propose, occurs when cytoskeletal elements of the axon cannot enter the shortened axon and "dam up" between the nucleus and axon hillock. As a consequence, we suggest that Nissl body-free axonal cytoskeleton accumulates between the nucleus and axon, displaces Nissl body-containing cytoskeleton, and produces central chromatolysis in that region of the cell.
Current and future developments in managed care in the United States and implications for Europe
Authors: Lagoe Ronald , Aspling Deborah L , Westert Gert P
Published: March 2005

The paper reviews and evaluates current and future approaches to cost containment in the United States. Managed care was once seen as an effective approach to supporting health care quality while containing costs in the USA. In recent years payors started to look in other directions, since prospects for limiting expenses faded. Nowadays consumer driven health plans seem to be on the rise. The reasons for the decline of managed care, the growing popularity of the consumer driven health plans and the implications for Europe are discussed.
Acute poisoning cases admitted to a university hospital emergency department in Diyarbakir, Turkey
Authors: Güloglu Cahfer , Kara Ismail Hamdi
Published: March 2005

Aim: This study was conducted to determine the biological effects of acute poisoning, the nature of agents involved and the pattern of poisoning in Diyarbakir City, in the Southeast Anatolian region of Turkey, during 2000. Method: Hospital records of all admissions to the Emergency Department (ED) of Dicle University Hospital following acute poisoning were revised and all data from January to December 2000 were analysed. The present study included 44 (25.9%) male (M) and 126 (74.1%) female (F), a total of 170 patients. The M/F ratio was 1.0/3.5. Results: The mean age of patients was 23.39±6.3 years; 63 (37.1%) of them were under 20 years of age and 147 (86.5%) were under 30 years of age. Most intoxication cases occurred during the summer season (93 of 170 patients). On a monthly basis, admissions during April, May and July were most common (24, 26 and 30 patients, respectively). Sixty-two (36.5%) cases involved accidental poisoning while 108 (63.5%) involved deliberate poisoning. In suicide attempts, intoxications were more common in females (77 cases, 71.3%, P < 0.05), and in unmarried persons (74 cases, 68.5%, P < 0.05). There were only two deaths (1.2%) among the 170 admissions of acute poisonings. One of the deaths was due to pesticide poisoning and the other was due to medical drug abuse. Tachycardia (59, 34.7%), vomiting (55, 32.4%) and loss of consciousness (42, 24.7%) were frequently observed, whereas hypersecretion (15, 8.8%), bradycardia (5, 2.9%), convulsion (8, 4.7%) and hypertension (2, 1.2%) were less frequent. Among pesticide poisoning cases the incidence of convulsion (6, 10.2%), miosis (6, 10.2%), and hypersecretion (12, 20.3%) were significantly higher when compared to other cases (P–0.018, P B < 0.0001 and P B < 0.0001, respectively). Conclusion: In the Southeast Anatolian region of Turkey, pesticide intoxication is common especially among young, unmarried females and most of these intoxications are intentional self-poisonings. The annual rate of poisoning-related ED visits and mortality were found to be within expected ranges; psychoactive agents being the most common cause.
A competitive ELISA detecting 7-methylguanosine adduct induced by N-nitrosodimethylamine exposure
Authors: Niot-Mansart Vanessa , Muhamedi Arbana , Arnould Jean-Pierre
Published: March 2005

N-Nitrosodimethylamine is a chemical compound known to be carcinogenic to animals and probably to humans. It is widespread and it can be found in food, tobacco smoke and in industrial emissions, such as in the rubber industry. N-Nitrosodimethylamine exerts its biological effects after metabolic activation by forming methylating nucleic acids in DNA. The most formed adduct is 7-methylguanosine. Our laboratory has developed and validated a competitive enzyme-linked immunosorbent assay in order to detect this adduct in DNA exposed to N-nitrosodimethylamine in vitro or in vivo. The imidazole ring-opening (iro) of 7-methylguanosine was required because of its stability. When 7-methylguanosine iro and serum were incubated at 48C, the assay was 35 times more sensitive than at 378C (50% inhibition at 37 fmol 7-methylguanosine iro per well at 48C and 1.28 pmol at 378C) with a lower limit of detection at 1.58 fmol 7-methylguanosine iro. This assay is reproducible, can be routinely performed and is sensitive enough to detect 7-methylguanosine adduct in DNA samples from human exposed to N-nitrosodimethylamine. We aim to use this method in further studies on epidemiological assessment in people at high risk, such as smokers.
Formate kinetics in methanol poisoning
Authors: Hantson P , Haufroid V , Wallemacq P
Published: March 2005

Objective: The objective is to describe the kinetics of formate, the main toxic metabolite of methanol, in a series of consecutive patients treated in the same intensive care unit for severe methanol poisoning. Methods: The charts of the patients admitted between 1987 and 2001 were reviewed. Inclusion criteria were: a history of deliberate methanol ingestion, with a blood methanol concentration greater than 20 mg/dL (6.2 mmol/L) or a high anion gap metabolic acidosis. Indications for hemodialysis were: blood methanol concentration>50 mg/dL (15.8 mmol/L), metabolic acidosis (bicarbonate < 15 mmol/L, arterial pH < 7.30), visual toxicity. Antidotal therapy included ethanol administration in 22 cases, and fomepizole in three cases. Serial blood measurements were obtained for pH, bicarbonate, methanol and formate. Endogenous and hemodialysis elimination half-lives were calculated as t1/2=0.693/Ke. Fick principle was applied for hemodialysis clearance calculation. Results: The records of 25 methanol poisoned patients were analysed. Among them, 18 patients had sufficient data to allow accurate determinations of formate kinetics. Formate half-life elimination during hemodialysis was 1.809 ± 0.78 h, which was statistically different from the values observed before or in the absence of dialysis (6.049 ± 3.26 h, P=0.004). The mean hemodialysis formate clearance rate calculated in eight cases was 1769 ± 43 mL/min. A rebound in plasma formate concentration was observed in three patients after the discontinuation of hemodialysis. Conclusions: In accordance with previous isolated case reports and in contrast with a recent case series, our data document that hemodiaysis is effective in reducing formate elimination half-life. The impact on clinical outcome is still debatable.
Phase III Southwest Oncology Group 9415/Intergroup 0153 Randomized Trial of Fluorouracil, Leucovorin, and Levamisole Versus Fluorouracil Continuous Infusion and Levamisole for Adjuvant Treatment of Stage III and High-Risk Stage II Colon Cancer
Authors: Poplin Elizabeth A. , Benedetti Jacqueline K. , Estes Norman C. , Haller Daniel G. , Mayer Robert J. , Goldberg Richard M. , Weiss Geoffrey R. , Rivkin Saul E. , Macdonald John S.
Published: March 2005

Purpose

Modest toxicity and possibly enhanced activity makes continuous-infusion fluorouracil (FU) an attractive alternative to FU plus leucovorin (FU/LV) for the adjuvant treatment of colorectal cancer. Intergroup trial 0153 (Southwest Oncology Group trial 9415) was developed to compare the efficacy of continuous-infusion FU (CIFU) plus levamisole to FU/LV plus levamisole in the adjuvant treatment of high-risk Dukes' B2 and C1 or C2 colon cancer.

Patients and Methods

After surgery, patients were randomly assigned to CIFU 250 mg/m2/d for 56 days every 9 weeks for three cycles or FU 425 mg/m2 and LV 20 mg/m2 daily for 5 days every 28 to 35 days for six cycles. All patients received levamisole 50 mg tid for 3 days every other week. The primary end point was overall survival (OS).

Results

The study closed in December 1999 after an interim analysis demonstrated little likelihood of CIFU showing superiority to FU/LV within the stipulated hazard ratio. A total of 1,135 patients were registered. At least one grade 4 toxicity occurred in 39% of patients receiving FU/LV and 5% of patients receiving CIFU. However, almost twice as many patients receiving CIFU discontinued therapy early compared with those receiving FU/LV. The 5-year OS is 70% (95% CI, 66% to 74%) for FU/LV and 69% (95% CI, 64% to 73%) for CIFU. The corresponding 5-year disease-free survival (DFS) is 61% (95% CI, 56% to 65%) and 63% (95% CI, 59% to 68%), respectively. For all patients, 5-year OS is 83%, 74%, and 55%; 5-year DFS is 78%, 67%, and 47% for N0, N1, and N2-3, respectively.

Conclusion

CIFU had less severe toxicity but did not improve DFS or OS in comparison with bolus FU/LV.
Psychological Impact of Genetic Testing for Hereditary Nonpolyposis Colorectal Cancer
Authors: Gritz Ellen R. , Peterson Susan K. , Vernon Sally W. , Marani Salma K. , Baile Walter F. , Watts Beatty G. , Amos Christopher I. , Frazier Marsha L. , Lynch Patrick M.
Published: March 2005

Purpose

This study examines the impact of hereditary nonpolyposis colorectal cancer (HNPCC) genetic test results on psychological outcomes among cancer-affected and -unaffected participants up to 1 year after results disclosure.

Patients and Methods

A total of 155 persons completed study measures before HNPCC genetic testing, and at 2 weeks and 6 and 12 months after disclosure of test results.

Results

Mean scores on all outcome measures remained stable and within normal limits for cancer-affected participants, regardless of mutation status. Among unaffected carriers of HNPCC-predisposing mutations, mean depression, state anxiety, and cancer worries scores increased from baseline to 2 weeks postdisclosure and decreased from 2 weeks to 6 months postdisclosure. Among unaffected noncarriers, mean depression and anxiety scores did not differ, but cancer worries scores decreased during the same time period. Affected and unaffected carriers had higher mean test-specific distress scores at 2 weeks postdisclosure compared with noncarriers in their respective groups; scores decreased for affected carriers and all unaffected participants from 2 weeks to 12 months postdisclosure. Classification of participants into high- versus low-distress clusters using mean scores on baseline psychological measures predicted significantly higher or lower follow-up scores, respectively, on depression, state anxiety, quality of life, and test-specific distress measures, regardless of mutation status.

Conclusion

Although HNPCC genetic testing does not result in long-term adverse psychological outcomes, unaffected mutation carriers may experience increased distress during the immediate postdisclosure time period. Furthermore, those with higher levels of baseline mood disturbance, lower quality of life, and lower social support may be at risk for both short- and long-term increased distress.
Phase I and Pharmacologic Study of 17-(Allylamino)-17-Demethoxygeldanamycin in Adult Patients With Solid Tumors
Authors: Grem Jean L. , Morrison Geraldine , Guo Xiao-Du , Agnew Elizabeth , Takimoto Chris H. , Thomas Rebecca , Szabo Eva , Grochow Louise , Grollman Frank , Hamilton J. Michael , Neckers Len , Wilson Richard H.
Published: March 2005

Purpose

To determine the clinical toxicities of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) given as a 1-hour infusion daily for 5 days every 3 weeks.

Patients and Methods

Nineteen patients received 17-AAG over six dose levels (10 to 56 mg/m2) using an accelerated titration scheme. Drug levels of 17-AAG were determined by high-performance liquid chromatography. Biologic effects of 17-AAG were monitored by changes in the content of target proteins by immunoblot analysis of lysates prepared from peripheral-blood mononuclear cells.

Results

Toxicity was acceptable at doses up to 28 mg/m2. The cohort was expanded to three patients at 40 mg/m2 because a second occurrence of grade 2 hepatic transaminitis occurred. Two of six assessable patients who received 56 mg/m2 had reversible, grade 3 hepatic transaminitis. Five additional patients were enrolled at 40 mg/m2; none had dose-limiting toxicity. The maximum plasma concentrations (Cmax) of 17-AAG at 40 and 56 mg/m2 were 1,724 and 2,046 ng/mL, respectively; the average plasma exposures (AUC) were 2,809 and 6,708 hours·ng/mL, respectively. Less than 3% of the daily dose was excreted into the urine. Clearance did not correlate with body-surface area. Possible biologic activity was suggested by apparent increased protein content of either glucose-related 78 kd protein or heat shock protein 70 with ≥ 14 mg/m2 and decreased protein content of either Lck or Raf1 with ≥ 28 mg/m2 of 17-AAG.

Conclusion

17-AAG 40 mg/m2 (median dose, 70 mg) was well tolerated when given daily for 5 days every 3 weeks.
Pulses of Prolactin Promoter Activity Depend on a Noncanonical E-Box that Can Bind the Circadian Proteins CLOCK and BMAL1
Authors: Leclerc Gilles M. , Boockfor Fredric R.
Published: March 2005

Recent findings from our laboratory and those of others demonstrated that prolactin gene expression (PRL-GE) oscillates in single living mammotropes, but little information is available on the molecular processes that contribute to this phenomenon. To elucidate the source of this activity, we generated a series of constructs containing decreasing lengths of the PRL promoter fused to a luciferase reporter gene. These constructs were injected into single cells and assayed for photonic activity. We found pulse activity with all plasmids tested, even with the smallest promoter fragment of 331 bp. Sequence analysis of this fragment identified two potential E-boxes (elements known to bind CLOCK and BMAL1 circadian proteins). Furthermore, RT-PCR of PRL cells (pituitary, MMQ, and GH3) revealed expression of clock and bmal1 as well as five other clock genes (per1, per2, cry1, cry2, and tim), suggesting that the circadian system may function in PRL cells. Next, we mutated the core sequences of both E-boxes within the 2.5-kb PRL promoter and found that only mutation of the E-box133 completely abolished PRL-GE pulses. EMSAs revealed that CLOCK and BMAL1 were able to bind to the E-box133 site in vitro. Our results demonstrate that PRL-GE pulses are dependent on a specific E-box binding site in the PRL promoter. Moreover, the indication that CLOCK/BMAL1 can bind to this site suggests that these circadian proteins, either alone or in conjunction with other factors, may regulate intermittent PRL promoter activity in mammotropes, perhaps by acting as a temporal switch for the on/off expression of PRL.
Minireview: Hexose-6-Phosphate Dehydrogenase and Redox Control of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity
Authors: Hewitt Kylie N. , Walker Elizabeth A. , Stewart Paul M.
Published: March 2005

Hexose-6-phosphate dehydrogenase (H6PDH) is a microsomal enzyme that is able to catalyze the first two reactions of an endoluminal pentose phosphate pathway, thereby generating reduced nicotinamide adenine dinucleotide phosphate (NADPH) within the endoplasmic reticulum. It is distinct from the cytosolic enzyme, glucose-6-phosphate dehydrogenase (G6PDH), using a separate pool of NAD(P)+ and capable of oxidizing several phosphorylated hexoses. It has been proposed to be a NADPH regenerating system for steroid hormone and drug metabolism, specifically in determining the set point of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity, the enzyme responsible for the activation and inactivation of glucocorticoids. 11β-HSD1 is a bidirectional enzyme, but in intact cells displays predominately oxo-reductase activity, a reaction requiring NADPH and leading to activation of glucocorticoids. However, in cellular homogenates or in purified preparations, 11β-HSD1 is exclusively a dehydrogenase. Because H6PDH and 11β-HSD1 are coexpressed in the inner microsomal compartment of cells, we hypothesized that H6PDH may provide 11β-HSD1 with NADPH, thus promoting oxo-reductase activity in vivo. Recently, several studies have confirmed this functional cooperation, indicating the importance of intracellular redox mechanisms for the prereceptor control of glucocorticoid availability. With the increased interest in 11β-HSD1 oxo-reductase activity in the pathogenesis and treatment of several human diseases including insulin resistance and the metabolic syndrome, H6PDH represents an additional novel candidate for intervention.
Test of a service profit chain model in the retail banking sector
Authors: Gelade Garry A. , Young Stephen
Published: March 2005

Research has shown that organizational subunits where employee perceptions are favourable enjoy superior business performance. The service profit chain model of business performance (Heskett, Sasser, & Schlesinger, 1997) has identified customer satisfaction as a critical intervening variable in this relationship. This paper examines the relationships between organizational climate, employee attitudes, customer satisfaction, and sales performance in the retail‐banking sector. The role of customer satisfaction as a mediator between employee attitudes and sales performance is examined in a large sample of bank branches, spanning multiple organizations. Mediation effects are found, which border on significance when the sample size is large, but the effects seem to be too small to be of practical importance. It is argued that alternative formulations of the service profit chain model may provide more powerful explanations of the link between employee attitudes and business performance.
Work‐group and organizational support: A test of distinct dimensions
Authors: Self Dennis R. , Holt Daniel T. , Schaninger William S.
Published: March 2005

Using data from 467 members of a large firm in the United States, this paper found that perceived work‐group support is a distinct construct from perceived organizational support. To reinforce the uniqueness of the constructs, the work‐group and organizational support constructs exhibited meaningful, differential relationships with six of eight variables reflecting different levels of exchange relationships and commitments. The implications of these findings are discussed.
Confirmatory factor analysis of the Cybernetic coping scale
Authors: Brough Paula , O'Driscoll Michael , Kalliath Thomas
Published: March 2005

The Ways of Coping Questionnaire (WCQ; Folkman & Lazarus, 1985) remains one of the widely used measures of self‐report coping behaviours, despite an acknowledgement of its relatively poor psychometric properties. In contrast, the Cybernetic coping scale (CCS; Edwards & Baglioni, 1993) appears to have improved psychometric characteristics, but is scarcely employed within published research. To examine the factor structure and criterion validity of the CCS, a longitudinal study was conducted using a diverse sample of New Zealand employees from a range of organizations. Using confirmatory factor analysis, the CCS was found to have construct validity over time. However, a 14‐item CCS model produced the best goodness‐of‐fit and improved item properties. The implications of this improved CCS are discussed in terms of longitudinal research designs, and the necessity for the inclusion of robust self‐report coping measures.
The role of leader‐member exchanges in mediating the relationship between locus of control and work reactions
Authors: Martin R. , Thomas G. , Charles K. , Epitropaki O. , McNamara R.
Published: March 2005

The relationship between locus of control, the quality of exchanges between subordinates and leaders (LMX), and a variety of work‐related reactions (intrinsic/extrinsic job satisfaction, work‐related well‐being, and organizational commitment) are examined. It was predicted that people with an internal locus of control develop better quality relations with their manager and this, in turn, results in more favourable work‐related reactions. Results from two different samples (N=404, and N=51) supported this prediction, and also showed that LMX either fully, or partially, mediated the relationship between locus of control and all the work‐related reactions.
Officially recorded convictions for probationers: The relationship with self‐report and supervisory observations
Authors: Farrall Stephen
Published: March 2005

Objectives. For the past 20–25 years the assessment of the outcomes of probation supervision and its associated variants has relied upon officially recorded offending as the chief determinant of ‘success’ and ‘failure’. A recent assessment of the impact of accredited programmes aimed at reducing offending called for reconviction rates to be supplemented with other outcome measures to give a more accurate picture of treatment effectiveness.

Methods. Self‐reports of offending are one such alternative outcome measure, and this paper responds to recent calls for developments in this field. This paper throws further light on the frequency of offending by probationers during their probation orders, the extent to which their officers knew of this offending and the relationship between self‐reported offending and subsequent convictions.

Results. The data suggest that about a half of the probationers committed at least one offence during the time they were on probation and that about a third of the probationers reported that they had committed more than four offences during this same time. In the main, probation officers reports mirrored the reports gained from the probationers. Generally speaking, the relationship between self‐reported offending and officially recorded convictions was also very close. However, this varied by the offences/convictions under consideration.

Conclusion. There were slightly more probationers found guilty of property offences than had admitted to such offending during their interviews. The explanation for this appeared to have been deliberate concealment on the part of the probationer, rather than recall failure.