bluuebunny/crossref_metadata_2025 huggingface dataset:
The assessment of craving: psychometric properties, factor structure and a revised version of the Alcohol Craving Questionnaire (ACQ)
Authors: Raabe Almut , Grüsser Sabine M. , Wessa Michèle , Podschus Jan , Flor Herta
Published: January 2005

Aims  The goal of the present study was to examine the psychometric properties and factor structure of the Alcohol Craving Questionnaire (ACQ).

Design and participants  The German version of the ACQ was administered to a sample of 243 alcohol‐dependent or alcohol‐abusing subjects. A subgroup of the sample (n = 46) completed the German translation of the Obsessive Compulsive Drinking Scale (OCDS) and the ACQ a second time.

Measurements  To validate the factor models, confirmatory factor analyses (CFA) were carried out. Examination of the psychometric properties of the ACQ included the analysis of the item characteristics to exclude non‐sensitive items, an exploratory factor analysis of the remaining items and calculation of internal consistency, test–retest reliability and convergent validity.

Findings  Neither of the two models showed a satisfactory correspondence. An exploratory factor analysis of a revised version of the ACQ (ACQ‐R), based on the psychometric properties of the items, revealed two stable factors (‘urge and intention to drink alcohol’ and ‘reinforcement’) with high internal consistency, test–retest reliability and convergent validity. The model fit was also excellent in the CFA.

Conclusions  The ACQ‐R is a reliable and valid instrument to assess alcohol craving. However, the ACQ‐R lacks items related to loss of control. Therefore a multi‐dimensional assessment, e.g. the combination of the ACQ‐R and the OCDS, is recommended.
Does alcohol advertising promote adolescent drinking? Results from a longitudinal assessment
Authors: Ellickson Phyllis L. , Collins Rebecca L. , Hambarsoomians Katrin , McCaffrey Daniel F.
Published: January 2005

Aims  To examine the relationship between exposure to different forms of alcohol advertising and subsequent drinking among US adolescents and assess whether exposure to an alcohol and drug prevention program mitigates any such relationship.

Design  Regression models with multiple control variables examined the relationship between exposure to alcohol advertising in grade 8 and grade 9 drinking for two groups of South Dakotan adolescents: (1) seventh‐grade non‐drinkers (n = 1206) and (2) seventh‐grade drinkers (n = 1905). Interactions between the intervention program and the significant advertising predictors were tested.

Setting  Forty‐one middle schools in South Dakota, USA.

Participants  A total of 3111 seventh‐graders followed through grade 9.

Measurements  Advertising variables were constructed for four types of alcohol advertising—television, in‐store displays, magazines and concession stands. Other predictors tested included measures tapping social influences, social bonds, problem behavior, alcohol beliefs, television exposure and demographics.

Findings  For seventh‐grade non‐drinkers, exposure to in‐store beer displays predicted drinking onset by grade 9; for seventh‐grade drinkers, exposure to magazines with alcohol advertisements and to beer concession stands at sports or music events predicted frequency of grade 9 drinking. Although exposure to television beer advertising had a significant bivariate relationship with alcohol use for grade 7 non‐drinkers, it was not a significant predictor of drinking for either group in multivariate analyses. Participation in the prevention program, ALERT Plus, reduced future drinking for both groups and counteracted the effect of in‐store beer displays.

Conclusions  Several forms of alcohol advertising predict adolescent drinking; which sources dominate depends on the child's prior experience with alcohol. Alcohol prevention programs and policies should help children counter alcohol advertising from multiple sources and limit exposure to these sources.
Laryngeal muscle fibre types
Authors: Hoh J. F. Y.
Published: January 2005

The internal laryngeal muscles have evolved to subserve the highly specialized functions of airways protection, respiration, and phonation. Their contractile properties, histochemistry, biochemical properties, myosin heavy chain (MyHC) expression and their regulation by nerves and hormones are reviewed and compared with limb muscle fibres. Cricothyroid, the vocal cord tensor, is limb‐like in MyHC composition and fibre type properties, while the vocal fold abductor and adductors are allotypically different, with capacity for expressing an isoform of MyHC that is kinetically faster than the fastest limb MyHC. In rats and rabbits the faster isoform is the extraocular (EO) MyHC, while in carnivores, it is the IIB MyHC. These adaptations enable the abductor and adductor muscles to remain always faster than the cricothyroid as the latter changes in speed during evolution to match changing metabolic and respiratory rates in relation to scaling with body mass. Such phylogenetic plasticity is vital to the airways protection and respiratory functions of these muscles. The posterior cricoarythenoid, the abductor muscle, is tonically driven during expiration, and consequently has a slower fibre type profile than the principal adductor, the thyroarythenoid. The human thyroarythenoid appears not to express EO or IIB MyHC significantly, but is unique in expressing the slow‐tonic MyHC. The concepts of allotype and phylogenetic plasticity help to explain differences in fibre type between limb and laryngeal muscles and between homologous laryngeal muscles in different species. Laryngeal muscle fibres exhibit physiological plasticity as do limb muscles, being subject to neural and hormonal modulation.
A novel form of pRb expressed during normal myelopoiesis and in tumour‐associated macrophages
Authors: Liu H. P. , Thompson A. M. , Macleod K. F.
Published: January 2005

Abstract.  The retinoblastoma (Rb) tumour suppressor promotes cell cycle exit, terminal differentiation and survival during normal development and is functionally inactivated in most human cancers. We have identified a novel myeloid‐specific form of retinoblastoma protein (pRb), termed ΔRb‐p70, that exists in vivo as an N‐terminally truncated form of full‐length pRb. ΔRb‐p70 appears to be the product of alternative translation and is expressed in primary myeloid cells in fetal liver, bone marrow and spleen. It is also expressed in the human myelomonocytic cell line U937 and is down‐regulated as U937s are induced to differentiate. We have also detected ΔRb‐p70 expression in primary human breast tumours and we have determined that ΔRb‐p70 is specifically expressed in tumour‐associated macrophages. These data identify a novel mechanism for regulating pRb expression that is unique to the myeloid system.
Leptin, cell proliferation and crypt fission in the gastrointestinal tract of intravenously fed rats
Authors: FitzGerald A. J. , Mandir N. , Goodlad R. A.
Published: January 2005

Abstract.  Many peptides, hormones and growth factors have been implicated in the control of cell renewal in the gastrointestinal epithelium. Leptin is present in the stomach and salivary glands and leptin receptors are seen throughout the gut. Leptin can stimulate mitogen‐activated protein kinase activity in vitro and short‐term infusion has been reported to have a proliferative action on the colon in vivo, suggesting a biological link between obesity, physical activity and colon cancer. Food intake is one of the most important determinants of intestinal mucosal cell renewal, thus any direct effects of leptin on the gut may be hidden. This problem has been avoided experimentally by maintaining animals on total parenteral nutrition (TPN). Male Wistar rats were anaesthetized and cannulae were inserted into the jugular vein to deliver the TPN diet to which had been added 0, 0.5, 2.5, or 10 mg/kg of recombinant murine leptin. Orally fed rats were also studied. After 6 days of treatment, all animals were injected with vincristine and killed 2 h later. Tissue weight was recorded and crypt cell proliferation (arrested metaphases) and crypt fission were scored in ‘microdissected’ crypts. Leptin infusion led to a small decrease in body weight and in the weight of the caecum. Intestinal cell proliferation was significantly reduced by TPN when compared to the orally fed rats, but the addition of leptin had no effect on the small intestine or colon. Crypt fission was also significantly lowered in the TPN group. Fission was slightly but significantly increased in the proximal and mid‐colon of the leptin‐treated rats, but was decreased in the distal colon. Although leptin did not significantly alter cell proliferation, it had significant effects on the process of crypt fission in the colon, which varied according to the exact locality.
Effect of stem cell mobilization with cyclophosphamide plus granulocyte colony‐stimulating factor on morphology of haematopoietic organs in mice
Authors: Szumilas P. , Barcew K. , Baśkiewicz‐Masiuk M. , Wiszniewska B. , Ratajczak M. Z. , Machaliński B.
Published: January 2005

Abstract.  Both granulocyte colony‐stimulating factor (G‐CSF) and cyclophosphamide (CY) are employed in the clinic as mobilizing agents to stimulate the egress of haematopoietic stem/progenitor cells (HSPC) from bone marrow (BM) into peripheral blood (PB). However, although both compounds are effective, the simultaneous administration of G‐CSF + CY allows for optimal mobilization. The aim of this study was to compare morphological changes in major haematopoietic organs in mice mobilized by G‐CSF + CY. We employed the standard G‐CSF + CY mobilization protocol, in which mice were injected at day 0 with a single dose of CY followed by daily injection of G‐CSF for 6 consecutive days. We noticed that the cytoreductive effect of CY on BM and spleen tissue was compensated at day 2 by the pro‐proliferative effect of G‐CSF. Furthermore, as evidenced by histological examination of BM sections at day 4, egress of haematopoietic cells from BM was accelerated by 2 days as compared to mobilization by G‐CSF or CY alone; also, by day 6 there was accumulation of early haematopoietic (Thy‐1low c‐kit+) cells in the spleens and livers of mobilized animals. This implies that HSPC that are mobilized from BM and circulate in PB may ‘home’ to peripheral organs. We envision that such an accumulation of these cells in the spleen (which is a major haematopoietic organ in mouse) allows them to participate in haematopoietic reconstitution. Their homing to other sites (for example the liver) is evidence that BM‐derived stem cells are playing a pivotal role in organ/tissue regeneration. The potential involvement of major chemoattractants for stem cells, like stromal‐derived factor‐1 which is induced by CY in various regenerating organs such as the liver, requires further study. We conclude that inclusion of CY into mobilization protocols on the one hand efficiently increases the egress of HSPC from the BM, but on the other hand may lead to the relocation of BM stem cell pools to peripheral tissues.
A constitutively active GPCR retains its G protein specificity and the ability to form dimers
Authors: Ladds Graham , Davis Kevin , Das Anamika , Davey John
Published: January 2005

G protein‐coupled receptors (GPCRs) are cell surface proteins which help to regulate the physiology of all the major organ systems within higher eukaryotes. They are stimulated by multiple ligands and activate a range of effector molecules to bring about changes in cell behaviour. The use of constitutively active mutants (CAMs) of GPCRs has enabled a better understanding of receptor activation as CAMs exhibit ligand‐independent signalling negating the use of ligands. Here we introduce the fission yeast Schizosaccharomyces pombe as a host for producing CAMs, by describing the isolation and characterization of constitutive mutants of the P‐factor receptor (Mam2). One mutant Mam2[P261L] contained a single‐amino‐acid substitution (Pro261 to Leu) within a region of high homology in GPCRs. Substitution of this proline leads to an 18‐fold increase in ligand‐independent signalling. We utilized Mam2[P261L] to investigate CAM activity by demonstrating that Mam2[P261L] is efficiently trafficked to the cell surface where it can form fully functional oligomeric complexes with the native receptor. Mam2[P261L] also retains the G protein specificity (RG‐profile) of the native receptor and only induces constitutive signalling in the same G proteins. Finally, evidence is provided to indicate that CAM activity results from a reduction in the kinetics of G protein binding. This is the first time that S. pombe has been utilized for isolating and characterizing CAMs and the techniques employed will complement the current systems available for studying these important receptors.
Carbapenem antibiotic biosynthesis in Erwinia carotovora is regulated by physiological and genetic factors modulating the quorum sensing‐dependent control pathway
Authors: McGowan Simon J. , Barnard Anne M. L. , Bosgelmez Gulgun , Sebaihia Mohammed , Simpson Natalie J. L. , Thomson Nicholas R. , Todd Daniel E. , Welch Martin , Whitehead Neil A. , Salmond George P. C.
Published: January 2005

Erwinia carotovora produces the β‐lactam antibiotic, carbapenem, in response to a quorum sensing signalling molecule, N‐(3‐oxohexanoyl)‐ l‐homoserine lactone (OHHL). We have mapped the OHHL‐dependent promoter upstream of the first of the biosynthetic genes, carA. We have also analysed the effect on this promoter of the known genetic regulators of carbapenem expression, carR, carI (encoding homologues of LuxR and LuxI respectively) and hor (encoding a SlyA/MarR‐like transcriptional regulator). We describe a previously unknown promoter located within the carA‐H operon. This promoter does not respond to CarR and is required for quorum sensing‐independent expression of the carbapenem resistance determinants encoded by the carFG genes. We have mapped the carR, carI and hor transcription start points, shown that CarR is positively autoregulated in the presence of OHHL, and have demonstrated negative feedback affecting transcription of carI. In addition, various environmental  and physiological factors were shown to impinge on the transcription of the car biosynthetic genes. The nature of the carbon source and the temperature of growth influence carbapenem production by modulating the level of the OHHL signalling molecule, and thereby physiologically fine‐tune the quorum sensing regulatory system.
Recoding in Archaea
Authors: Cobucci‐Ponzano Beatrice , Rossi Mosè , Moracci Marco
Published: January 2005

Standard decoding of the genetic information into polypeptides is performed by one of the most sophisticated cell machineries, the translating ribosome, which, by following the genetic code, ensures the correspondence between the mature mRNA and the protein sequence. However, the expression of a minority of genes requires programmed deviations from the standard decoding rules, globally named recoding. This includes ribosome programmed –/+1 frameshifting, ribosome hopping, and stop codon readthrough. Recoding in Archaea was unequivocally demonstrated only for the translation of the UGA stop codon into the amino acid selenocysteine. However, a new recoding event leading to the 22nd amino acid pyrrolysine and the preliminary reports on a gene regulated by programmed −1 frameshifting have been recently described in Archaea. Therefore, it appears that the study of this phenomenon in Archaea is still at its dawn and that most of the genes whose expression is regulated by recoding are still uncharacterized.
The polo‐like kinase PLKA is required for initiation and progression through mitosis in the filamentous fungus Aspergillus nidulans
Authors: Bachewich Catherine , Masker Kathryn , Osmani Stephen
Published: January 2005

Polo‐like kinases (PLK) function during multiple stages of mitotic progression and in cytokinesis. We identified and cloned a PLK homologue in Aspergillus nidulans, plkA, which is the first PLK reported in a filamentous fungus and the largest member of the PLK family to date. As plkA was essential, the effects of overexpression and localization of protein in living cells were explored to determine PLKA function. Overexpression of PLKA permitted hyphal formation, but blocked nuclear division in interphase. In NIMA or NIMT temperature‐sensitive backgrounds, overexpression of PLKA impaired normal entry into mitosis upon release from restrictive temperature, supporting a role for PLKA during G2/M. In the few mitotic cells present, spindles were monopolar or disorganized, and chromatin condensation and segregation were impaired, suggesting additional roles for PLKA in spindle formation and in chromosome dynamics. Consistent with this, green fluorescent protein (GFP)‐tagged PLKA could localize to the spb during interphase, and to the spb and nucleus throughout mitosis. Intriguingly, PLKA remained on the spb during telophase and into G1, in contrast to other PLK. In addition, spb localization was independent of NIMA function, unlike that demonstrated in Schizosaccharomyces pombe where PLK localization to the spb required the NIMA homologue Fin1. PLKA was not detected at cortical, septation‐associated sites, and overexpression did not drive septum formation, also in contrast to that observed with other PLK. Therefore, PLKA is important for multiple events during mitosis, similar to PLK in higher organisms, but exhibits differences in size, localization and influence on septation/cytokinesis, suggesting additional novel regulatory features.
In vitro reconstitution of a trimeric complex of DivIB, DivIC and FtsL, and their transient co‐localization at the division site in Streptococcus pneumoniae
Authors: Noirclerc‐Savoye Marjolaine , Le Gouëllec Audrey , Morlot Cécile , Dideberg Otto , Vernet Thierry , Zapun André
Published: January 2005

DivIB, DivIC and FtsL are bacterial proteins essential for cell division, which show interdependencies for their stabilities and localization. We have reconstituted in vitro a trimeric complex consisting of the recombinant extracellular domains of the three proteins from Streptococcus pneumoniae. The extracellular domain of DivIB was found to associate with a heterodimer of those of DivIC and FtsL. The heterodimerization of DivIC and FtsL was artificially constrained by fusion with interacting coiled‐coils. Immunofluorescence experiments showed that DivIC is always localized at mid‐cell, in contrast to DivIB and FtsL, which are co‐localized with DivIC only during septation. Taken together, our data suggest that assembly of the trimeric complex DivIB/DivIC/FtsL is regulated during the cell cycle through controlled formation of the DivIC/FtsL heterodimer.
The expression of a novel antisense gene mediates incompatibility within the large repABC family of α‐proteobacterial plasmids
Authors: MacLellan Shawn R. , Smallbone Laura A. , Sibley Christopher D. , Finan Turlough M.
Published: January 2005

Large extrachromosomal replicons in many members of the α‐proteobacteria encode genes that are required for plant or animal pathogenesis or symbiosis. Most of these replicons encode repABC genes that control their replication and faithful segregation during cell division. In addition to its chromosome, the plant endosymbiont Sinorhizobium meliloti also maintains the 1.4 Mb pSymA and 1.7 Mb pSymB symbiotic megaplasmids both of which are repABC‐type replicons. In all repABC loci that have been characterized, an apparently untranslated intergenic region between the repB and repC genes encodes a strong incompatibility determinant (referred to as incα). Here we report the isolation of mutations within the incα regions of pSymA and pSymB that eliminate incompatibility. These mutations map to and inactivate a promoter in the intergenic region that drives the expression of an approximately 56 nucleotide untranslated RNA molecule that mediates incompatibility. This gene, that we have named incA, is transcribed antisense to the repABC genes. Our analysis suggests that the incA gene is conserved in repABC loci from a diverse spectrum of bacteria.
GlcP constitutes the major glucose uptake system of Streptomyces coelicolor A3(2)
Authors: Van Wezel Gilles P. , Mahr Kerstin , König Miriam , Traag Bjørn A. , Pimentel‐Schmitt Elisângela F. , Willimek Andreas , Titgemeyer Fritz
Published: January 2005

We provide a functional and regulatory analysis of glcP, encoding the major glucose transporter of Streptomyces coelicolor A3(2). GlcP, a member of the Major Facilitator Superfamily (MFS) of bacterial and eucaryotic sugar permeases, was found to be encoded twice at two distinct loci, glcP1 and glcP2, located in the central core and in the variable right arm of the chromosome respectively. Heterologous expression of GlcP in Escherichia coli led to the full restoration of glucose fermentation to mutants lacking glucose transport activity. Biochemical analysis revealed an affinity constant in the low‐micromolar range and substrate specificity for glucose and 2‐deoxyglucose. Deletion of glcP1 but not glcP2 led to a drastic reduction in growth on glucose reflected by the loss of glucose uptake. This correlated with transcriptional analyses, which showed that glcP1 transcription was strongly inducible by glucose, while glcP2 transcripts were barely detectable. In conclusion, GlcP, which is the first glucose permease from high G+C Gram‐positive bacteria characterized at the molecular level, represents the major glucose uptake system in S. coelicolor A3(2) that is indispensable for the high growth rate on glucose. It is anticipated that the activity of GlcP is linked to other glucose‐mediated phenomena such as carbon catabolite repression, morphogenesis and antibiotic production.
Receptor binding studies disclose a novel class of high‐affinity inhibitors of the Escherichia coli FimH adhesin
Authors: Bouckaert Julie , Berglund Jenny , Schembri Mark , De Genst Erwin , Cools Lieve , Wuhrer Manfred , Hung Chia‐Suei , Pinkner Jerome , Slättegård Rikard , Zavialov Anton , Choudhury Devapriya , Langermann Solomon , Hultgren Scott J. , Wyns Lode , Klemm Per , Oscarson Stefan , Knight Stefan D. , De Greve Henri
Published: January 2005

Mannose‐binding type 1 pili are important virulence factors for the establishment of Escherichia coli urinary tract infections (UTIs). These infections are initiated by adhesion of uropathogenic E. coli to uroplakin receptors in the uroepithelium via the FimH adhesin located at the tips of type 1 pili. Blocking of bacterial adhesion is able to prevent infection. Here, we provide for the first time binding data of the molecular events underlying type 1 fimbrial adherence, by crystallographic analyses of the FimH receptor binding domains from a uropathogenic and a K‐12 strain, and affinity measurements with mannose, common mono‐ and disaccharides, and a series of alkyl and aryl mannosides. Our results illustrate that the lectin domain of the FimH adhesin is a stable and functional entity and that an exogenous butyl α‐ d‐mannoside, bound in  the  crystal  structures,  exhibits  a  significantly better affinity for FimH (Kd = 0.15 µM) than mannose (Kd = 2.3 µM). Exploration of the binding affinities of α‐ d‐mannosides with longer alkyl tails revealed affinities up to 5 nM. Aryl mannosides and fructose can also bind with high affinities to the FimH lectin domain, with a 100‐fold improvement and 15‐fold reduction in affinity, respectively, compared with mannose. Taken together, these relative FimH affinities correlate exceptionally well with the relative concentrations of the same glycans needed for the inhibition of adherence of type 1 piliated E. coli. We foresee that our findings will spark new ideas and initiatives for the development of UTI vaccines and anti‐adhesive drugs to prevent anticipated and recurrent UTIs.
From fundamental studies of sporulation to applied spore research
Authors: Barák Imrich , Ricca Ezio , Cutting Simon M.
Published: January 2005

Sporulation in the Gram‐positive bacterium, Bacillus subtilis, has been used as an excellent model system to study cell differentiation for almost half a century. This research has given us a detailed picture of the genetic, physiological and biochemical mechanisms that allow bacteria to survive harsh environmental conditions by forming highly robust spores. Although many basic aspects of this process are now understood in great detail, including the crystal and NMR structures of some of the key proteins and their complexes, bacterial sporulation still continues to be a highly attractive model for studying various cell processes at a molecular level. There are several reasons for such scientific interest. First, some of the complex steps in sporulation are not fully understood and/or are only described by ‘controversial’ models. Second, intensive research on unicellular development of a single microorganism, B. subtilis, left us largely unaware of the multitude of diverse sporulation mechanisms in many other Gram‐positive endospore and exospore formers. This diversity would likely be increased if we were to include sporulation processes in the Gram‐negative spore formers. Spore formers have great potential in applied research. They have been used for many years as biodosimeters and as natural insecticides, exploited in the industrial production of enzymes, antibiotics, used as probiotics and, more, exploited as possible vectors for drug delivery, vaccine antigens and other immunomodulating molecules. This report describes these and other aspects of current fundamental and applied spore research that were presented at European Spores Conference held in Smolenice Castle, Slovakia, June 2004.
Genetic susceptibility screening in schools: attitudes of the school community towards hereditary haemochromatosis
Authors: Gason AA , Aitken MA , Metcalfe SA , Allen KJ , Delatycki MB
Published: January 2005

Carrier screening to provide reproductive options has been offered to students in the school setting for a number of years; however, genetic susceptibility screening for disease predisposition has not been introduced to the school community. Experience has shown that the success of a population‐based programme relies on the community's acceptance. Therefore, we sought to establish the Australian secondary school community's attitudes towards genetic susceptibility screening in schools, with hereditary haemochromatosis as the model condition with an available prevention. School students, aged 15–18 (n = 748), completed a questionnaire immediately before and following an oral educational presentation. Their parents (n = 179) and staff (n = 89) received written information and returned a questionnaire by post. Semi‐structured interviews were with Government representatives. Attitudes towards genetic screening in schools and knowledge of genetic and clinical features of haemochromatosis, as well as the likelihood of accepting a genetic susceptibility test for haemochromatosis, were all measured. Participants were positive about genetic screening for disease susceptibility in schools. Their knowledge was high following education with no significant differences between participants of each group. Sixty‐eight percent of students would be likely to have the test if it were offered, with parents and staff, indicating that they would like the students to be offered a test, on average. Genetic susceptibility screening in schools is a novel concept. The results of our study indicate that it could be a public health success with the support of the community.
The developing limb and the control of the number of digits
Authors: Talamillo A , Bastida Mf , Fernandez‐Teran M , Ros Ma
Published: January 2005

Congenital malformations of the limbs are among the most frequent congenital anomalies found in humans, and they preferentially affect the distal part – the hand or foot. The presence of extradigits, a condition called polydactyly, is the most common limb deformity of the human hand and is the consequence of disturbances in the normal program of limb development. However, despite the extensive use of the developing limb as a classical developmental model, the cellular and genetic mechanisms that control the number and identity of the digits are not completely understood. The aim of this review is to introduce the reader to the current state of knowledge in limb development and to provide the necessary background for an understanding of how deviations from the normal developmental program may lead to polydactyly.
Significant overexpression of urokinase‐type plasminogen activator in pancreatic adenocarcinoma using real‐time quantitative reverse transcription polymerase chain reaction
Authors: NIELSEN AIQUN , SCARLETT CHRISTOPHER J , SAMRA JASWINDER S , GILL ANTHONY , LI YONG , ALLEN BARRY J , SMITH ROSS C
Published: January 2005

Background and Aims:  Overexpression of urokinase‐type plasminogen activator (uPA) has been shown to be strongly associated with an increased metastatic potential and poor prognosis in a variety of human malignancies. It was hypothesized that uPA would be overexpressed in highly metastatic pancreatic cancer. The aims of this study were to analyze uPA mRNA expression in pancreatic cancer and to correlate this to the expression of uPA protein and to the stage of the disease.

Methods:  Twenty‐one pancreatic adenocarcinoma, six ampullary carcinoma and 10 benign mucinous cystadenoma samples, all with adjacent normal tissue, were collected. uPA mRNA was measured using real‐time quantitative reverse transcription polymerase chain reaction. Localization of uPA within normal and pancreatic tumor sections was subsequently confirmed using immunohistochemistry.

Results:  The median and range of the ratios of uPA mRNA measures between tumor tissue and non‐involved pancreatic tissue was 17.1 (1.4–653.6) for pancreatic adenocarcinoma (P < 0.001), 3.9 (0.7–7.7) for ampullary carcinoma (P = 0.055) and 1.9 (0.6–5.9) for mucinous cystadenoma tissue (P = 0.052). uPA low tumors were associated with an exuberant stromal reaction, whereas uPA high tumors showed little stromal response. Immunohistochemistry confirmed that uPA protein was more prevalent in pancreatic adenocarcinoma tissue than in normal tissue and that it was membrane‐bound. uPA mRNA expression was significantly associated with poorly differentiated pancreatic cancers (P < 0.05) and positively associated with tumor stage.

Conclusions:  These observations suggest that significant overexpression of uPA correlates closely to the rapid progression and invasiveness of pancreatic cancer and that uPA may provide a future therapeutic target for pancreatic cancer treatment.
Diagnostic accuracy of the 13C‐urea breath test in children: Adjustment of the cut‐off value according to age
Authors: YANG HYE RAN , SEO JEONG KEE
Published: January 2005

Background and Aims: The 13C‐urea breath test (13C‐UBT) is a reliable non‐invasive method of diagnosing Helicobacter pylori infection in adults and children. However, only a few validation studies have been performed on the 13C‐UBT in very young children. The purpose of the present study was to evaluate the diagnostic accuracy of the 13C‐UBT according to age, and to determine the optimal cut‐off value in children.

Methods: A total of 307 13C‐UBT were performed in 274 children. All were compared with the results of endoscopic biopsy‐based methods to confirm H. pylori infection. Seventy‐five milligrams of 13C‐urea was ingested without a test meal. Two breath samples were collected at 0 and 30 min. The optimal cut‐off value of the 13C‐UBT was assessed by determining the sensitivity, specificity, false negative, and false positive results, at cut‐off values ranging from 2.0 to 10.0‰.

Results: The delta over baseline (DOB) values of the 13C‐UBT showed a significant negative correlation with age in both the H. pylori‐positive group (r = −0.309; P = 0.005) and the H. pylori‐negative group (r = −0.162; P = 0.015). High false positive results and low specificity were noted in children aged 6 years or less compared with children older than 6 years at a cut‐off value of 4.0‰ (false positives; 8.3%vs 0.85%, specificity; 89.8%vs 98.8%). After adjusting the cut‐off value, the optimal cut‐off values were found to be 4.0‰ in children older than 6 years and 7.0‰ in children aged 6 years or less.

Conclusions: The cut‐off value of the 13C‐UBT recommended regardless of age must be adjusted in preschool children to reduce the false positive results.
Rapid diagnosis of spontaneous bacterial peritonitis with leukocyte esterase reagent strips in a European and in an American center
Authors: SAPEY THIERRY , MENA EDWARD , FORT ERIC , LAURIN CHRISTINE , KABISSA DENIS , RUNYON BRUCE A , MENDLER MICHEL‐HENRY
Published: January 2005

Background:  Timely diagnosis and treatment of spontaneous bacterial peritonitis (SBP) are essential to survival. The purpose of the present paper was to evaluate leukocyte esterase reagent strips (Nephur‐Test and MultistixSG10) in the bedside diagnosis of SBP.

Methods:  Patients with cirrhotic ascites were prospectively included in France (center 1) and in the USA (center 2). Paracenteses were performed on admission and repeated as indicated. Bedside reagent strip testing was performed on the ascitic fluid and compared to manual cell count with differential and ascitic fluid culture. In center 1, the Nephur‐Test was tested in all cases, with dual testing with MultistixSG10 in a subgroup. In center 2, all cases had dual testing. Spontaneous bacterial peritonitis was defined as a polymorphonuclear ascites count ≥250/µL.

Results:  A total of 184 samples was obtained in 76 patients. Center 1 included 151 samples from 53 patients. Seven samples had SBP, obtained in six patients. Center 2 included 33 samples from 23 patients. Six samples had SBP, obtained in five patients. The sensitivity, specificity, positive and negative predictive value of the reagent strips were as follows. Center 1/Nephur‐Test: 86%, 100%, 100%, 99%; center 1/MultistixSG10: 100%, 100%, 100%, 100%; center 2/Nephur‐Test: 100%, 92.5%, 75%, 100%; center 2/MultistixSG10: 83%, 96%, 83%, 96%.

Conclusion:  Leukocyte esterase reagent strips may provide a rapid bedside diagnosis of SBP.
Exposure to continuous darkness ameliorates gastric and colonic inflammation in the rat: Both receptor and non‐receptor‐mediated processes
Authors: ÇEVÍK HÜLYA , ERKANLI GÖZDE , ERCAN FERÍHA , ÍŞMAN ÇAĞla A , YEĞEN BERRAK Ç
Published: January 2005

Background and Aim:  Melatonin is a hormone involved in the transduction of photoperiodic information, and appears to modulate a variety of neural and endocrine functions. The present study was designed to determine the impact of continuous darkness (CD) on acute gastric and colonic inflammation and the involvement of melatonin receptors in the darkness‐related alterations in oxidant gut injury.

Methods:  Rats were housed either in CD or in standardized light/dark (12/12 h) cycles for 15 days before the induction of colitis or gastric ulcer. Luzindole (MT2 receptor antagonist) was given at a dose of 0.25 mg/kg intraperitoneally 30 min before and 6 and 18 h following the induction of colitis with acetic acid or gastric ulcer with ethanol. Rats were decapitated at 24 h, and the colons and stomachs were removed for macroscopic scoring, histologic assessment and for the determination of tissue malondialdehyde and glutathione levels.

Results:  All inflammation parameters were increased by acetic acid‐induced colitis or ethanol‐induced gastric ulcer compared with the control group. Our results indicate that the severity of both gastric and colonic injury is reduced by a 2‐week exposure to CD prior to the induction of inflammatory event, while luzindole treatment reversed the protective effect of CD on the colonic and gastric injury. However, darkness‐related alterations in malondialdehyde and glutathione levels were not altered by luzindole.

Conclusion:  Although the CD‐induced amelioration of gut injury involves melatonin receptors, the direct antioxidant effects on melatonin appear to be independent of receptor activity.
13C‐Urea breath test: Reproducibility and association with the severity of Helicobacter pylori‐associated antral gastritis
Authors: MATTHEWS GEOFFREY M , CUMMINS ADRIAN G , LAWRENCE ANDREW , JOHNSON BRUCE , CAMPBELL FIONA , BUTLER ROSS N
Published: January 2005

Background: The purpose of the present paper was to assess the reproducibility of the 13C‐urea breath test (13C‐UBT) and its ability to reflect the level of Helicobacter pylori‐associated inflammation.

Methods: Asymptomatic H. pylori‐positive subjects (n = 21) performed the 13C‐UBT six times. The H. pylori‐positive symptomatic subjects (n = 55) performed the 13C‐UBT and had antral biopsies taken for histopathology, culture, urease activity assay and myeloperoxidase activity assay.

Results: No significant intraindividual variation in 13C‐UBT results were observed for the asymptomatic subjects. The 13C‐UBT results were significantly higher in symptomatic subjects with a moderate to severe gastritis compared to a mild gastritis and to no inflammation (34.5 ± 4.4 vs 17.7 ± 2.8 vs 1.7 ± 0.1, respectively, P < 0.01). The 13C‐UBT results significantly correlated with urease (r = 0.55) and myeloperoxidase activity (r = 0.82) but not with bacterial load.

Conclusion: The 13C‐UBT is a reproducible determinant of H. pylori infection and non‐invasively assesses the severity of antral inflammation.

© 2004 Blackwell Publishing Asia Pty Ltd
Gallbladder cancer in India: A dismal picture
Authors: BATRA YOGESH , PAL SUJOY , DUTTA USHA , DESAI PREMAL , GARG PRAMOD KUMAR , MAKHARIA GOVIND , AHUJA VINEET , PANDE GIRISH KUMAR , SAHNI PEUSH , CHATTOPADHYAY T K , TANDON RAKESH KUMAR
Published: January 2005

Background: Gallbladder cancer (GBC) is one of the most common gastrointestinal malignancies. The data regarding GBC are, however, limited.

Methods: Records of 634 patients with GBC over a 10‐year period were examined with regard to the clinical presentation, investigative findings, treatment, operative findings and outcome.

Results: The mean age of patients was 51 ± 11 years and men : women ratio was 0.36:1.00. Pain, jaundice and hepatomegaly were seen in 81.0%, 76.0% and 61.5% patients, respectively. On imaging, a mass replacing the gallbladder was seen in 73% patients. Gallstones were present in 54% patients. Surgery was carried out in 291 (46%) patients and endoscopic treatment in 72 (19%) patients but no intervention was carried out in the remaining patients because of disseminated disease. Among the patients who were operated on, 2.0% had stage I GBC, 3.4% stage II, 17.5% stage III, 47.0% stage IVa and 29.8% stage IVb. Radical resection was possible in 133 (46%) patients. The 30‐day mortality was 10% with most (90%) deaths in patients with stage IV disease. The median survival after simple cholecystectomy and radical surgery was 33.5 and 12.0 months, respectively. However, among those who underwent debulking, palliative bypass or exploratory laparotomy alone, the survival ranged between 1 and 3 months. Logistic regression analysis showed that only radical resection improved the long‐term survival (P < 0.05).

Conclusions: The majority of patients with GBC in India have advanced unresectable disease. Detection of GBC at an early stage is incidental and rare but is associated with long‐term survival. Radical surgery, when feasible, is the only option for achieving long‐term survival.

© 2005 Blackwell Publishing Asia Pty Ltd
Recognition of affect in facial expression using the Noh Mask Test: Comparison of individuals with schizophrenia and normal controls
Authors: MINOSHITA SEIKO , MORITA NOBUAKI , YAMASHITA TOSHIYUKI , YOSHIKAWA MAIKO , KIKUCHI TADASHI , SATOH SHINJI
Published: January 2005

Abstract  The purpose of the present study was to compare facial expression recognition in individuals with schizophrenia and normal controls using the Noh Mask Test. Fifteen men with schizophrenia and 15 normal controls were presented with a photograph of a Noh mask rotated either upward or downward from the neutral front‐facing position, and an emotion label, and were requested to judge whether the expression of the mask was congruent with the indicated emotion. Using multidimensional scaling, the facial expression of the Noh mask recognized by the patients and the healthy controls was analyzed in 3‐D: (i) Rejection–Attention; (ii) Pleasant–Unpleasant; and (iii) Awakening–Relaxation. Individuals with schizophrenia had difficulty recognizing that others had intentions of harming them. The Noh Mask Test was found to be useful in discriminating between individuals with schizophrenia and controls in the recognition of facial expression (discriminant ratio: 99.9%).
Are the patients with post‐transplant psychiatric consultation different from other medical–surgical consultation inpatients?
Authors: KISHI YASUHIRO , MELLER WILLIAM H. , SWIGART SUSAN E. , KATHOL ROGER G.
Published: January 2005

Abstract  The present study examines the characteristics of post‐transplant patients compared with non‐transplant patients seen by consultation psychiatrists. Medical records of 541 consecutive psychiatric consultation patients at a university teaching hospital in 2001 were reviewed. Of the 541 patients who were evaluated, 67 were post‐transplant patients. Post‐transplant psychiatric consultation is different in some aspects from other psychiatric consultation. Post‐transplant patients suffer complicated medical, psychiatric, and social burdens.
Alcohol drinking frequency is more directly associated with alcohol use disorder than alcohol metabolizing enzymes among male Japanese
Authors: NISHIYORI ATSUSHI , SHIBATA AKIRA , OGIMOTO ITSURO , UCHIMURA NAOHISA , EGAMI HIDEKI , NAKAMURA JUN , SAKATA RITSU , FUKUDA KATSUHIRO
Published: January 2005

Abstract  The development of alcohol use disorder (AUD) is related to various social, economic, cultural, environmental and hereditary factors. Several potential risk factors have been proposed for AUD in addition to alcohol consumption, including alcohol dehydrogenase2 (ADH2), acetaldehyde dehydrogenase2 (ALDH2), marital status, educational, occupational or past medical history (e.g. diabetes mellitus, hypertension, lung, digestive tract, or chronic liver disease) or smoking habits. The present study was performed to investigate the relationship between the aforementioned potential risk factors and AUD in Japan. A case–control study was performed on 153 male Japanese AUD patients and age‐, gender‐, or other confounder‐matched controls to investigate the relation multivariately between ADH2, ALDH2 or alcohol drinking and AUD. Genomic DNA were extracted from nail clippings by the guanidium method, and genotyping of ADH2 and ALDH2 were performed using polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) methods. Univariate analyses by the conditional logistic regression model revealed statistically significant odds ratios due to ADH2*1/1 genotype, ALDH2*1/1 genotype, middle school as the final school attended, longest occupations as farmers, fishermen, craftsmen, miners, production process or construction workers, and past histories of chronic liver disease and AUD. However, multivariate analyses under a hierarchically well‐formulated model strategy with interaction and confounding assessment indicated that (i) heavy alcohol intake was a significant risk factor (odds ratio per 1.0 g of daily ethanol intake; 1.096, 95% confidence interval; 1.026–1.171) for developing AUD after adjusting for other confounders; and (ii) ADH2*1/1 genotype and ALDH2*1/1 genotype were not risk factors after adjusting for daily ethanol intake and other confounders. The present study shows that AUD was more directly and strongly associated with alcohol drinking than with alcohol metabolizing enzymes among male Japanese.
Occupation and social experience: Factors influencing attitude towards people with schizophrenia
Authors: ISHIGE NAOKO , HAYASHI NAOKI
Published: January 2005

Abstract  The purpose of the present study was to examine the role of occupation and social experience as factors determining the attitude of psychiatric care workers and other workers from various backgrounds toward people with schizophrenia. To measure the attitude of 786 subjects from six occupational groups toward people with schizophrenia, the evaluation scale applying semantic differential technique and the modified Social Rejection Scale were used, which assess two aspects of the attitude: affective acceptance and social distancing, respectively. The results of the two scales from the six groups were similar on the whole. Public health nurses showed the most accepting attitude in both scales. Psychiatric nurses and local welfare commissioners were the second and the third groups in affective acceptance, and the third and the second in socially accepting behavior, respectively. There was no significant difference in attitude among the rest of the groups (non‐psychiatric care workers, professional probation officers and non‐care workers). These results can be understood in terms of the workers’ experience of contact with people with schizophrenia, and education and other support opportunities. The importance of positive contact experiences and the means for facilitation of an accepting attitude in psychiatric care workers and other workers need to be stressed.
Evaluating community attitudes to people with schizophrenia and mental disorders using a case vignette method
Authors: TANAKA GORO , INADOMI HIROYUKI , KIKUCHI YASUKI , OHTA YASUYUKI
Published: January 2005

Abstract  Utilizing the case vignette method, community attitudes about people with schizophrenia and mental disorders, and perceived causes of and images regarding schizophrenia were investigated. Participants comprised 1596 respondents living in the area covered by the K health center in N prefecture. The survey utilized the Mental Disorder Prejudice Scale, a case vignette, and other basic attributes. The case vignette survey yielded the following results: when asked about a landlord refusing to rent an apartment to the vignette subject, approximately 80% of respondents agreed with the landlord's decision. However, when asked about necessary conditions for the vignette subject to live in an apartment independently, only 2.4% of respondents chose ‘difficult under any circumstance’. Approximately half of the respondents chose the following conditions: ‘periodic visits to the hospital’, ‘availability of a system where people can discuss and address any problems that might arise’ and ‘attending a sheltered workshop or making attempts to rehabilitate’. Regarding acceptance as a neighbor after meeting the listed conditions, most respondents stated they would ‘treat him just like any other neighbor’ (47.3%), followed by ‘help as much as possible in times of need’ (36.3%). In other words, approximately 80.0% of respondents were willing to have the vignette subject as their neighbor. In addition, many respondents thought that schizophrenia is caused by problems in interpersonal relationships (64.8%) and represents an unstable disease (69.9%). When asked about having the subject as a neighbor, respondents were more willing to accept him as a neighbor after clarifying conditions for living arrangements.
Childhood histories of attention‐deficit hyperactivity disorders in Japanese methamphetamine and inhalant abusers: Preliminary report
Authors: MATSUMOTO TOSHIHIKO , KAMIJO ATSUSHI , YAMAGUCHI AKIKO , ISEKI EIZO , HIRAYASU YOSHIO
Published: January 2005

Abstract  The present study examined childhood histories of attention‐deficit hyperactivity disorder (ADHD) in 54 methamphetamine and 12 inhalant abusers using the Wender Utah Rating Scale. The inhalant abusers experienced initial drinking at a younger age than methamphetamine abusers (P = 0.038). The Wender Utah Rating Scale score was significantly higher in the inhalant abusers than in the methamphetamine abusers (P = 0.013) although 83.3% of inhalant and 55.6% of methamphetamine abusers had higher scores than the cut‐off for ADHD. These findings suggest that drug abuse is associated with childhood ADHD, and that inhalant abusers have a higher incidence of childhood ADHD than methamphetamine abusers.