bluuebunny/crossref_metadata_2025_split huggingface dataset:
The regulation of veratridine‐stimulated electrogenic ion transport in mouse colon by neuropeptide Y (NPY), Y1 and Y2 receptors
Authors: Hyland Niall P , Cox Helen M 
Published: August 2005

Neuropeptide Y (NPY) is a prominent enteric neuropeptide with prolonged antisecretory effects in mammalian intestine. Veratridine depolarises neurons consequently causing epithelial anion secretion across mouse colon mucosa. Our aim was to characterise functionally, veratridine‐stimulated mucosal responses and to determine the roles for NPY, Y1, and Y2 receptors in modulating these neurogenic effects.
Colon mucosae (with intact submucous innervation) from wild‐type mice (+/+) and knockouts lacking either NPY (NPY−/−), Y1−/− or Y2−/− were placed in Ussing chambers and voltage clamped at 0 mV. Veratridine‐stimulated short‐circuit current (Isc) responses in +/+, Y1 or Y2 antagonist pretreated +/+ colon, Y1−/− and NPY−/− colon were insensitive to cholinergic blockade by atropine (At; 1 μM) and hexamethonium (Hex; 10 μM). Tetrodotoxin (TTX, 100 nM) abolished veratridine responses, but had no effect upon carbachol (CCh) or vasoactive intestinal polypeptide (VIP)‐induced secretory responses.
To establish the functional roles for Y1 and Y2 receptors, +/+ tissues were pretreated with either the Y1 or Y2 receptor antagonist (BIBO3304 (300 nM) or BIIE0246 (1 μM), respectively) and veratridine responses were compared with those from Y1−/− or Y2−/− colon. Neither BIBO3304 nor Y1−/− altered veratridine‐induced secretion, but Y1 agonist responses were abolished in both preparations. In contrast, the Y2 antagonist BIIE0246 significantly amplified veratridine responses in +/+ mucosa. Unexpectedly, NPY−/− colon exhibited significantly attenuated veratridine responses (between 1 and 5 min).
We demonstrate that electrogenic veratridine responses in mouse colon are noncholinergic and that NPY can act directly upon epithelia, a Y1 receptor effect. The enhanced veratridine response observed in +/+ tissue following BIIE0246, indicates that Y2 receptors are located on submucosal neurons and that their activation by NPY will inhibit enteric noncholinergic secretory neurotransmission.
We also demonstrate Y1 and Y2 receptor‐mediated antisecretory tone in +/+ colon and show selective loss of each in Y1 and Y2 null colon respectively. In NPY−/− tissue, only Y1‐mediated tone was present, this presumably being mediated by endogenous endocrine peptide YY. Y2 tone was absent from NPY−/− (and Y2−/−) colon and we conclude that NPY activation of neuronal Y2 receptors attenuates secretory neurotransmission thereby providing an absorptive electrolyte tone in isolated colon.

British Journal of Pharmacology (2005) 146, 712–722. doi:10.1038/sj.bjp.0706368
Volume regulation in cortical collecting duct cells: role of AQP2
Authors: Ford Paula , Rivarola Valeria , Chara Osvaldo , Blot‐Chabaud Marcel , Cluzeaud Françoise , Farman Nicolette , Parisi Mario , Capurro Claudia 
Published: August 2005

Background information. The renal CCD (cortical collecting duct) plays a role in final volume and concentration of urine by a process that is regulated by the antidiuretic hormone, [arginine]vasopressin. This hormone induces an increase in water permeability due to the translocation of AQP2 (aquaporin 2) from the intracellular vesicles to the apical membrane of principal cells. During the transition from antidiuresis to diuresis, CCD cells are exposed to changes in environmental osmolality, and cell‐volume regulation may be especially important for the maintenance of intracellular homoeostasis. Despite its importance, cell‐volume regulation in CCD cells has not been widely investigated. Moreover, no studies have been carried out till date to evaluate the putative role of AQPs during this process in renal cells.Results. In the present study, we have studied the regulatory cell‐volume responses to hypo‐osmotic or hyperosmotic challenges in two CCD cell lines: one not expressing AQPs and the other stably transfected with AQP2. We have used a fluorescent probe technique in which the acquisition of single‐cell kinetic data can be simultaneously recorded with the intracellular pH. Experiments with hyperosmotic mannitol media demonstrated that, independent of AQP2 expression, CCD cells shrink but fail to show regulatory volume increase, at least under the studied conditions. In contrast, under hypo‐osmotic shocks, regulatory volume decrease occurs and the activation of these mechanisms is more rapid in AQP2 transfected cells. This regulatory response takes place in parallel with intracellular acidification, which is faster in cells expressing AQP2. The acidification and the initial regulatory volume decrease response were inhibited by glibenclamide and BaCl2 only in AQP2 cells.Conclusions. These results suggest that increases in the osmotic water permeability due to the expression of AQP2 are critical for a rapid activation of regulatory volume decrease mechanisms, which would be linked to cystic fibrosis transmembrane conductance regulator and to barium‐sensitive potassium channels.
Dynamics of the Ins(1,4,5)P3 receptor during polarization of MDCK cells
Authors: Cruttwell Caroline , Bernard Jérôme , Hilly Mauricette , Nicolas Valérie , Tunwell Richard E.A. , Mauger Jean‐Pierre 
Published: August 2005

Background information. The uneven distribution of the Ins(1,4,5)P3R [Ins(1,4,5)P3 receptor] within the ER (endoplasmic reticulum) membrane generates spatially complex Ca2+ signals. The ER is a dynamic network, which allows the rapid diffusion of membrane proteins from one part of the cell to another. However, little is known about the localization and the dynamics of the Ins(1,4,5)P3R in the ER of living cells. We have used a MDCK (Madin—Darby canine kidney) clone stably expressing the Ins(1,4,5)P3R1‐GFP (where GFP stands for green fluorescent protein) to investigate the effect of cell polarity on the lateral mobility of the Ins(1,4,5)P3R.Results. In non‐confluent MDCK cells, the chimaera is homogeneously distributed throughout the ER and the nuclear envelope. FRAP (fluorescence recovery after photobleaching) experiments showed that the receptor can move freely in the ER with a diffusion constant (D=0.01 μm2/s) approx. ten times lower than other ER membrane proteins. In confluent polarized cells, two populations of receptor can be defined: one population is distributed in the cytoplasm and is mobile but with a slower diffusion constant (D=0.004 μm2/s) compared with non‐confluent cells, whereas the other population is concentrated at the periphery of the cells and is apparently immobile.Conclusions. The observed differences in the mobility of the Ins(1,4,5)P3R are most probably due to its interactions with stable protein complexes that form at the periphery of the polarized cells.
Modulation of lipid metabolism by n−3 polyunsaturated fatty acids in gestational diabetic rats and their macrosomic offspring
Authors: Soulimane-Mokhtari Nassima A. , Guermouche Baya , Yessoufou Akadiri , Saker Myrieum , Moutairou Kebirou , Hichami Aziz , Merzouk Hafida , Khan Naim A. 
Published: August 2005

The time course of changes in lipid metabolism by dietary n−3 PUFAs (polyunsaturated fatty acids) in streptozotocin-induced diabetic rats during pregnancy (days 12 and 21) and their macrosomic offspring at birth (day 0) and through adulthood (days 60 and 90) was studied with respect to adipose tissue, liver and serum lipid concentrations, and fatty acid composition. Glucose and insulin levels were also assessed in order to characterize the diabetic state of macrosomic offspring. Pregnant diabetic and control rats were fed either an Isio-4 or EPAX diet (enriched with n−3 PUFA). The same diets were also consumed by pups at weaning. Compared with control rats, during pregnancy diabetic rats had a significant elevation in liver and serum triacylglycerol (triglyceride) and cholesterol concentrations. At birth, macrosomic pups had higher serum insulin and glucose levels than control pups. The macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight and lipid content through the first 12 weeks of age. The macrosomic pups from diabetic rats fed the Isio-4 diet also showed a significant enhancement in liver and serum triacylglycerol and cholesterol levels at birth and during adulthood. Feeding the EPAX diet to diabetic mothers as well as their macrosomic pups increased serum and liver levels of EPA (eicospentaenoic acid) and DHA (docosahexaenoic acid) with a reduction in arachidonic acid. The EPAX diet induced a significant decrease in liver and serum triacylglycerol and cholesterol concentrations in mothers during pregnancy and in their macrosomic pups during adulthood. Since the EPAX diet improves lipid anomalies considerably in diabetic mothers and their macrosomic offspring, it may prevent long-term metabolic abnormalities associated with macrosomia.
Association for Medical Education and Research in Substance Abuse
Authors: Samet Jeffrey H. , Galanter Marc , Bridden Carly , Lewis David C. 
Published: August 2005

ABSTRACTThe Association for Medical Education and Research in Substance Abuse (AMERSA) is a multi‐disciplinary organization committed to health professional faculty development in substance abuse. In 1976, members of the Career Teachers Training Program in Alcohol and Drug Abuse, a US federally funded multi‐disciplinary faculty development program, formed AMERSA. The organization grew from 59 founding members, who were primarily medical school faculty, to over 300 health professionals from a spectrum of disciplines including physicians, nurses, social workers, dentists, allied health professionals, psychologists and other clinical educators who are responsible for advancing substance abuse education. AMERSA members promote substance abuse education among health professionals by developing curricula, promulgating relevant policy and training health professional faculty to become excellent teachers in this field. AMERSA influences public policy by offering standards for improving substance abuse education. The organization publishes a peer‐reviewed, quarterly journal, Substance Abuse, which emphasizes research on the education and training of health professions and also includes original clinical and prevention research. Each year, the AMERSA National Conference brings together researchers and health professional educators to learn about scientific advances and exemplary teaching approaches. In the future, AMERSA will continue to pursue this mission of advancing and supporting health professional faculty who educate students and trainees to address substance abuse in patients and clients.
Comparing the effectiveness of two types of cooling blankets for febrile patients
Authors: Loke Alice Y , Chan Helen CL , Chan Tony MF 
Published: August 2005

AbstractA randomized controlled trial was conducted to compare the effectiveness of airflow‐ and waterflow‐cooling blankets for febrile patients in intensive care unit. More patients in the airflow than in the waterflow‐cooling blanket group reached the desired temperature of <38°C at the end of 8 h (94·1 versus 60·0%, χ2 = 2·86, P = 0·047). Patients in the airflow blanket group also took less time than those in the waterflow blanket group to achieve the desired temperature (3·1 and 5·7 h, respectively, U = 2·00, P < 0·001). These findings suggest that the airflow blanket is the cooling blanket of choice for febrile patients when external cooling is needed.
The measurement and application of thrombin generation
Authors: Baglin Trevor 
Published: August 2005

SummaryIt is the capacity to generate thrombin, and the enzymatic work that thrombin does, that determines blood coagulability. Therefore, measurement of the enzymatic work potential of thrombin provides a method for quantifying the composite effect of the multiple factors that determine coagulation capacity. The application of measurement of thrombin generation to clinical decision making has been hampered by numerous technical difficulties and pitfalls, many of which have now been overcome. Technical advances now permit rapid, reproducible measurement. A review of clinical studies performed to date indicates the need to appreciate the precise methodology used in each case and the need to consider standardisation in future studies. Applying thrombin generation measurement to clinical decision making will require up‐to‐date estimates of risks relating to the disorder and the intended therapeutic intervention. Ultimately management studies will be required if the clinical utility of measurement of thrombin generation is to be proven.
Indirubin, a Chinese anti‐leukaemia drug, promotes neutrophilic differentiation of human myelocytic leukaemia HL‐60 cells
Authors: Suzuki Kazuhiro , Adachi Reiko , Hirayama Akiko , Watanabe Hidemi , Otani Saki , Watanabe Yuka , Kasahara Tadashi 
Published: August 2005

SummaryIndirubin, a purple vegetable dye, is a traditional Chinese medicine for myelocytic leukaemia. Indirubin inhibits cyclin‐dependent protein kinases (CDKs) and is present in human urine and serum. When indirubin was present during the neutrophilic differentiation of human myelocytic leukaemia HL‐60 cells, it augmented superoxide production triggered by opsonized zymosan (OZ) by the terminally differentiated HL‐60 cells. It also augmented the calcium response to OZ stimulation, and HL‐60 cell chemotaxis evoked by interleukin‐8 (IL‐8, CXCL8) and formylpeptide. In addition, indirubin induced marked IL‐8 release by the cells during differentiation and the cells differentiated with indirubin had typical neutrophilic properties, deformed nuclei and granules. Use of stable cloned HL‐60 cells that contained a reporter vector for monitoring the activity of the transcription factor PU.1, which acts specifically at the stage of promyelocyte differentiation into neutrophils and monocytes, revealed that indirubin has a potent promoting activity on intracellular PU.1. Indirubin enhanced the expression of typical neutrophil proteins, including granulocyte‐colony stimulating factor receptor, the β2‐integrin subunit CD18, the NADPH‐oxidase subunit p47phox, and the IL‐8 receptor CXCR1, all are controlled by PU.1. Indirubin also inhibited CDK2‐dependent phosphorylation of retinoblastoma protein during neutrophilic differentiation. These results suggest that indirubin augments the neutrophilic differentiation of human myelocytic leukaemia HL‐60 cells through inhibition of CDK2 and activation of PU.1.
Gene conversions are a common cause of von Willebrand disease
Authors: Gupta P. K. , Adamtziki E. , Budde U. , Jaiprakash M. , Kumar H. , Harbeck‐Seu A. , Kannan M. , Oyen F. , Obser T. , Wedekind I. , Saxena R. , Schneppenheim R. 
Published: August 2005

Summaryvon Willebrand disease (VWD), the most common inherited bleeding disorder, is very heterogeneous, both in its phenotype and genotype. One particular molecular mechanism of VWD is due to recombination events between the true gene and its pseudogene on chromosome 22. We assessed the frequency and extension of such events in 50 multi‐ethnic index patients with severe VWD type 3 and in five index patients with VWD type 2M Vicenza. One additional unclassified patient had been diagnosed with possible VWD in Russia solely on a clinical basis. Gene conversions, previously thought to be rare events, were identified in >10% of our study population: in six multi‐ethnic patients with severe VWD type 3, in one patient with VWD type 2M Vicenza and the Russian patient was finally diagnosed with VWD type 2B New York/Malmoe. Our results suggest a significant contribution of this particular molecular mechanism to the manifestation of VWD. The location of the gene conversions, their extension and their occurrence as homozygous, compound heterozygous or heterozygous mutations determines the resulting phenotype.
Primary mediastinal large B‐cell lymphoma: optimal therapy and prognostic factor analysis in 141 consecutive patients treated at memorial Sloan Kettering from 1980 to 1999
Authors: Hamlin Paul A. , Portlock Carol S. , Straus David J. , Noy Ariela , Singer Andrew , Horwitz Steven M. , OConnor Owen A. , Yahalom Joachim , Zelenetz Andrew D. , Moskowitz Craig H. 
Published: August 2005

SummaryPrimary mediastinal large B‐cell lymphoma (PMLBL) is a distinct clinicopathological entity with unclear prognostic factors and optimal treatment approach. To elucidate an optimal treatment and identify predictive factors, a retrospective analysis of 141 consecutive patients was undertaken. Patients received cyclophosphamide, hydroxydaunomycin, Oncovin, prednisone (CHOP)‐like therapy, the non‐Hodgkin lymphoma (NHL)‐15 regimen or upfront autologous stem cell transplantation (ASCT) on Institutional Review Board approved trials or according to the institutional guidelines. Evaluation included lactate dehydrogenase, International Prognostic Index (IPI) assessment, computed tomography scan and gallium imaging. With a median follow‐up of 10·9 years, event‐free survival (EFS) and overall survival (OS) was 50% and 66% respectively. EFS/OS for CHOP/CHOP‐like, NHL‐15 and upfront ASCT was 34/51%, 60/84% and 60/78% respectively. CHOP/CHOP‐like regimens had inferior EFS and OSversusNHL‐15 or upfront ASCT (P < 0·001). A total of 23% of patients received radiotherapy. Multivariate analysis revealed the following outcome predictors: for EFS, greater than or equal to two extranodal sites and initial therapy received (NHL‐15 or upfront ASCT); for OS, only initial therapy with NHL‐15. We conclude: (i) dose‐dense chemotherapy with NHL‐15 may be superior to CHOP for PMLBL; (ii) The impact of consolidative radiotherapy requires randomised controlled trials; (iii) The age‐adjusted IPI did not predict survival in this analysis; (iv) high‐dose chemotherapy/ASCT should be reserved for upfront anthracycline‐based therapy failure or in clinical trials for high‐risk patients.
Lineage‐specific engraftment and outcomes after T‐cell‐depleted peripheral blood stem cell transplant with Flu/Cy/TBI conditioning
Authors: Montero Aldemar , Savani Bipin N. , Kurlander Roger , Read Elizabeth J. , Leitman Susan F. , Childs Richard , Solomon Scott R. , John Barrett A. 
Published: August 2005

SummarySixty patients with haematological malignancies received a myeloablative regimen of total body irradiation, cyclophosphamide and fludarabine followed by a T‐cell‐depleted peripheral blood stem cell transplant from a human leucocyte antigen identical sibling. To improve donor immune function, 1 × 107 CD3+ cells/kg were added‐back between d 45 and 100. T‐cell and myeloid chimaerism were monitored regularly to evaluate the effect of T‐cell chimaerism on outcome. The major factor affecting outcome was disease risk, with significantly lower relapse and higher survival in 29 standard risk (SR) patients compared with 31 patients at high risk (HR) for treatment failure (relapse 4·8 ± 5% vs. 59 ± 11%, P < 0·0001, and overall survival 93 ± 5% vs. 39 ± 10%, P < 0·0001, respectively). Donor myeloid chimaerism reached ≥95% within 14 d of transplant, but in the first several months, donor T‐cell chimaerism was frequently mixed. Full T‐cell chimaerism was significantly more frequent in HR vs. SR patients. Landmark analysis at days 30 and 90 in HR patients with mixed versus full T‐cell chimaerism, showed relapse probabilities of 50·5 ± 14% vs. 70 ± 16% (P = 0·62) and 34·4 ± 20% vs. 58·8 ± 15% (P = 0·32) respectively. Early full T‐cell engraftment correlated with development of severe acute graft‐versus‐host disease (GVHD). However, mixed T‐cell chimaerism was favourable for reducing GVHD, and did not affect relapse in this small series.
Comparative genomic hybridisation identifies two variants of smoldering multiple myeloma
Authors: Rosiñol Laura , Carrió Ana , Bladé Joan , Queralt Rosa , Aymerich Marta , Cibeira MaTeresa , Esteve Jordi , Rozman Maria , Campo Elías , Montserrat Emili 
Published: August 2005

SummaryTwo variants of smoldering multiple myeloma (SMM) have been recognised: (i) an evolving type, characterised by a progressive increase in the M‐protein size and short time to progression to overt multiple myeloma (MM) and (ii) a non‐evolving type, with a long‐lasting, stable M‐protein and longer time to progression. Comparative genomic hybridisation (CGH) analyses in both subtypes of SMM (seven evolving and eight non‐evolving SMM) were performed. Evolving SMM showed cytogenetic changes consistent with those found in de novo symptomatic MM (1q gains, chromosome 13 deletions) while the non‐evolving variant showed no 1q gains and deletions were uncommon.
Validation of questions on asthma and wheeze in farming and anthroposophic children
Authors: Üblagger E. , Schreuer M. , Eder W. , Von Mutius E. , Benz M. R. , Braun‐Fahrländer C. , Moeller A. , Brunekreef B. , Schram D. , Wickman M. , Swartz J. , Pershagen G. , Riedler J. ,   on behalf of the PARSIFAL study group
Published: August 2005

SummaryBackground
In most epidemiological surveys the estimated prevalence of asthma is based on questionnaire responses, which may depend on the individual's perception as well as medical consulting habits in a given population. Therefore, measurement of bronchial hyper‐responsiveness as a key feature of asthma has been suggested as an objective parameter for asthma.Objective
The aim of the present study was to validate questionnaire responses on asthma and wheeze against bronchial response to hypertonic saline (HS) (4.5%) in populations previously shown to have a lower prevalence of asthma and allergies: farmers' children and children from anthroposophic families.Methods
Children whose parents had completed a written questionnaire in the cross‐sectional PARSIFAL‐study were drawn from the following four subgroups: ‘farm children’ (n=183), ‘farm reference children’ (n=173), ‘Steiner schoolchildren’ (n=243) and ‘Steiner reference children’ (n=179). Overall, 319 children with wheeze in the last 12 months and 459 children without wheeze in the last 12 months performed an HS challenge.Results
Odds ratios, sensitivity, specificity, likelihood ratios and measures of association did not differ significantly between the four subgroups. The correlation between the bronchial response to HS and wheeze and asthma questions was moderate and similar for farm children, farm reference children, Steiner schoolchildren and Steiner reference children (κ for ‘wheeze’: 0.25, 0.33, 0.31, 0.35, respectively, P=0.754, κ for ‘doctor's diagnosis of asthma’: 0.33, 0.19, 0.33, 032, respectively, P=0.499).Conclusion
The findings from this study suggest that the reliabilitiy of questionnaire responses on asthma and wheeze is comparable between farmers' children, children raised in families with anthroposophic lifestyle and their respective peers.
The effects of Anabaena spiroides (Cyanophyceae) exopolysaccharide on copper toxicity to Simocephalus serrulatus (Cladocera, Daphnidae)
Authors: NOGUEIRA PATRÍCIA F. M. , MELÃO MARIA DA G. G. , LOMBARDI ANA T. , VIEIRA ARMANDO A. H. 
Published: August 2005

Summary1. This work investigated the consumption of a microalgal (Anabaena spiroides) exopolysaccharide by the cladoceran Simocephalus serrulatus (Cladocera, Daphnidae) and its effect on copper toxicity.2. Total organic carbon concentration was used to quantify the microalgal exopolysaccharide. Both copper‐complexed exopolysaccharides and copper‐free exopolysaccharides were taken up by S. serrulatus.3. A reduction of free copper ions was obtained in the presence of A. spiroides exopolysaccharide. Copper toxicity (EC50) and zooplankton concentrations were inversely correlated to exopolysaccharide concentration in experimental media.4. An increase of free copper ions in experimental media was obtained after exopolysaccharide consumption, suggesting that S. serrulatus excreted copper to the surrounding environment.