bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactions between the megakaryocyte/platelet-specific β1 tubulin and the secretory leukocyte protease inhibitor SLPI suggest a role for regulated proteolysis in platelet functions
Authors: Schulze Harald , Korpal Manav , Bergmeier Wolfgang , Italiano Joseph E. , Wahl Sharon M. , Shivdasani Ramesh A. 
Published: August 2004

AbstractPlatelet-restricted β1 tubulin is required for optimal thrombopoiesis and discoid cell shape. To identify interacting factors, we used the divergent β1-tubulin C-terminus as the bait in a yeast 2-hybrid screen of megakaryocyte (MK) cDNAs. We isolated secretory leukocyte protease inhibitor (SLPI), a serine protease antagonist characterized principally as a secreted factor with multiple roles in inflammation. SLPI is expressed in MKs and platelets in 2 discrete compartments. One pool resides in punctate cytoplasmic structures, whereas a significant fraction localizes along peripheral microtubules (MTs) and is lost with cold-induced MT disruption or in β1 tubulin-/- platelets. These findings reveal unexpected interaction between a prominent cytoskeletal protein and an inhibitor of proteolysis. SLPI-/- mice show intact proplatelet formation, platelet numbers and shape, and marginal MT bands; thus, SLPI is not essential for thrombopoiesis. However, SLPI is released upon platelet activation, which also reverses its association with the resting marginal band. Platelet SLPI inhibits neutrophil elastase, an activity that is reduced when β1 tubulin is absent. We conclude that SLPI localizes in part along the MK and platelet MT cytoskeleton by virtue of specific interactions with β1 tubulin. SLPI may thus have unanticipated roles in MK and platelet functions, including regulated proteolysis after activation. (Blood. 2004;104:3949-3957)
The adaptor protein SH2D1A regulates signaling through CD150 (SLAM) in B cells
Authors: Mikhalap Svitlana V. , Shlapatska Larysa M. , Yurchenko Olga V. , Yurchenko Maria Y. , Berdova Ganna G. , Nichols Kim E. , Clark Edward A. , Sidorenko Svetlana P. 
Published: August 2004

AbstractThe CD150 receptor is expressed on activated T and B lymphocytes, dendritic cells, and monocytes. A TxYxxV/I motif in the CD150 cytoplasmic tail can bind different SH2-containing molecules, including tyrosine and inositol phosphatases, Src family kinases, and adaptor molecules. To analyze CD150-initiated signal transduction pathways, we used DT40 B-cell sublines deficient in these molecules. CD150 ligation on DT40 transfectants induced the extracellular signal-regulated kinase (ERK) pathway, which required SH2-containing inositol phosphatase (SHIP) but not SH2 domain protein 1A (SH2D1A). CD150-mediated Akt phosphorylation required Syk and SH2D1A, was negatively regulated by Lyn and Btk, but was SHIP independent. Lyn directly phosphorylated Y327 in CD150, but the Akt pathway did not depend on CD150 tyrosine phosphorylation and CD150-SHP-2 association. Analysis of CD150 and SH2D1A expression in non-Hodgkin and Hodgkin lymphomas revealed stages of B-cell differentiation where these molecules are expressed alone or coexpressed. Signaling studies in Hodgkin disease cell lines showed that CD150 is linked to the ERK and Akt pathways in neoplastic B cells. Our data support the hypothesis that CD150 and SH2D1A are coexpressed during a narrow window of B-cell maturation and SH2D1A may be involved in regulation of B-cell differentiation via switching of CD150-mediated signaling pathways. (Blood. 2004;104:4063-4070)
Platelets synthesize large amounts of active plasminogen activator inhibitor 1
Authors: Brogren Helén , Karlsson Lena , Andersson Maria , Wang Lingwei , Erlinge David , Jern Sverker 
Published: August 2004

AbstractPrevious studies have suggested that plasminogen activator inhibitor 1 (PAI-1) released from platelets convey resistance of platelet-rich blood clots to thrombolysis. However, the majority of PAI-1 in platelets is inactive and therefore its role in clot stabilization is unclear. Because platelets retain mRNA and capacity for synthesis of some proteins, we investigated if platelets can de novo synthesize PAI-1 with an active configuration. PAI-1 mRNA was quantified with real-time polymerase chain reaction and considerable amounts of PAI-1 mRNA were detected in all platelet samples. Over 24 hours, the amount of PAI-1 protein as determined by an enzyme-linked immunosorbent assay increased by 25% (P = .001). Metabolic radiolabeling with 35S-methionine followed by immunoprecipitation confirmed an ongoing PAI-1 synthesis, which could be further stimulated by thrombin and inhibited by puromycin. The activity of the newly formed PAI-1 was investigated by incubating platelets in the presence of tissue-type plasminogen activator (tPA). This functional assay showed that the majority of the new protein was in an active configuration and could complexbind tPA. Thus, there is a continuous production of large amounts of active PAI-1 in platelets, which could be a mechanism by which platelets contribute to stabilization of blood clots. (Blood. 2004;104:3943-3948)
Alternative mapping of probes to genes for Affymetrix chips
Authors: Gautier Laurent , Møller Morten , Friis-Hansen Lennart , Knudsen Steen 
Published: August 2004

Abstract
Background
Short oligonucleotide arrays have several probes measuring the expression level of each target transcript. Therefore the selection of probes is a key component for the quality of measurements. However, once probes have been selected and synthesized on an array, it is still possible to re-evaluate the results using an updated mapping of probes to genes, taking into account the latest biological knowledge available.

Methods
We investigated how probes found on recent commercial microarrays for human genes (Affymetrix HG-U133A) were matching a recent curated collection of human transcripts: the NCBI RefSeq database. We also built mappings and used them in place of the original probe to genes associations provided by the manufacturer of the arrays.

Results
In a large number of cases, 36%, the probes matching a reference sequence were consistent with the grouping of probes by the manufacturer of the chips. For the remaining cases there were discrepancies and we show how that can affect the analysis of data.

Conclusions
While the probes on Affymetrix arrays remain the same for several years, the biological knowledge concerning the genomic sequences evolves rapidly. Using up-to-date knowledge can apparently change the outcome of an analysis.
Subcellular distribution of the V-ATPase complex in plant cells, and in vivo localisation of the 100 kDa subunit VHA-a within the complex
Authors: Kluge Christoph , Seidel Thorsten , Bolte Susanne , Sharma Shanti S , Hanitzsch Miriam , Satiat-Jeunemaitre Beatrice , Roß Joachim , Sauer Markus , Golldack Dortje , Dietz Karl-Josef 
Published: August 2004

Abstract
Background
Vacuolar H+-ATPases are large protein complexes of more than 700 kDa that acidify endomembrane compartments and are part of the secretory system of eukaryotic cells. They are built from 14 different (VHA)-subunits. The paper addresses the question of sub-cellular localisation and subunit composition of plant V-ATPase in vivo and in vitro mainly by using colocalization and fluorescence resonance energy transfer techniques (FRET). Focus is placed on the examination and function of the 95 kDa membrane spanning subunit VHA-a. Showing similarities to the already described Vph1 and Stv1 vacuolar ATPase subunits from yeast, VHA-a revealed a bipartite structure with (i) a less conserved cytoplasmically orientated N-terminus and (ii) a membrane-spanning C-terminus with a higher extent of conservation including all amino acids shown to be essential for proton translocation in the yeast. On the basis of sequence data VHA-a appears to be an essential structural and functional element of V-ATPase, although previously a sole function in assembly has been proposed.

Results
To elucidate the presence and function of VHA-a in the plant complex, three approaches were undertaken: (i) co-immunoprecipitation with antibodies directed to epitopes in the N- and C-terminal part of VHA-a, respectively, (ii) immunocytochemistry approach including co-localisation studies with known plant endomembrane markers, and (iii) in vivo-FRET between subunits fused to variants of green fluorescence protein (CFP, YFP) in transfected cells.

Conclusions
All three sets of results show that V-ATPase contains VHA-a protein that interacts in a specific manner with other subunits. The genomes of plants encode three genes of the 95 kDa subunit (VHA-a) of the vacuolar type H+-ATPase. Immuno-localisation of VHA-a shows that the recognized subunit is exclusively located on the endoplasmic reticulum. This result is in agreement with the hypothesis that the different isoforms of VHA-a may localize on distinct endomembrane compartments, as it was shown for its yeast counterpart Vph1.
Cluster randomised trials in the medical literature: two bibliometric surveys
Authors: Bland J Martin 
Published: August 2004

Abstract
Background
Several reviews of published cluster randomised trials have reported that about half did not take clustering into account in the analysis, which was thus incorrect and potentially misleading. In this paper I ask whether cluster randomised trials are increasing in both number and quality of reporting.

Methods
Computer search for papers on cluster randomised trials since 1980, hand search of trial reports published in selected volumes of the British Medical Journal over 20 years.

Results
There has been a large increase in the numbers of methodological papers and of trial reports using the term 'cluster random' in recent years, with about equal numbers of each type of paper. The British Medical Journal contained more such reports than any other journal. In this journal there was a corresponding increase over time in the number of trials where subjects were randomised in clusters. In 2003 all reports showed awareness of the need to allow for clustering in the analysis. In 1993 and before clustering was ignored in most such trials.

Conclusion
Cluster trials are becoming more frequent and reporting is of higher quality. Perhaps statistician pressure works.
Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study
Authors: Chintamani  , Singhal Vinay , Singh JP , Lyall Ashima , Saxena Sunita , Bansal Anju 
Published: August 2004

Abstract
Background
Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins) brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer.

Methods
50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio). Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide) were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared.
Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was assessed using chi-square test and coefficient of correlation calculated by Pearson correlation coefficient.

Results
There was a statistically significant correlation observed between clinical, immunohistochemical response (bcl-2/bax ratio) and the drug-induced toxicity.

Conclusion
Responders also had significant toxicity while non-responders did not show significant toxicity following neoadjuvant chemotherapy. The chemotherapy-induced toxicity was observed to be a cost effective and reliable predictor of response to neo-adjuvant chemotherapy.
Factors associated with psychotropic drug use among community-dwelling older persons: A review of empirical studies
Authors: Voyer Philippe , Cohen David , Lauzon Sylvie , Collin Johanne 
Published: August 2004

Abstract
Background
In the many descriptive studies on prescribed psychotropic drug use by community-dwelling older persons, several sociodemographic and other factors associated with drug use receive inconsistent support.

Method
Empirical reports with data on at least benzodiazepine or antidepressant drug use in samples of older persons published between 1990 and 2001 (n = 32) were identified from major databases and analyzed to determine which factors are most frequently associated with psychotropic drug use in multivariate analyses. Methodological aspects were also examined.

Results
Most reports used probability samples of users and non-users and employed cross-sectional designs. Among variables considered in 5 or more reports, race, proximity to health centers, medical consultations, sleep complaints, and health perception were virtually always associated to drug use. Gender, mental health, and physical health status were associated in about two-thirds of reports. Associations with age, marital status, medication coverage, socioeconomic status, and social support were usually not observed.

Conclusions
The large variety of methods to operationalize drug use, mental health status, and social support probably affected the magnitude of observed relationships. Employing longitudinal designs and distinguishing short-term from long-term use, focusing on samples of drug users exclusively, defining drug use and drug classes more uniformly, and utilizing measures of psychological well-being rather than only of distress, might clarify the nature of observed associations and the direction of causality. Few studies tested specific hypotheses. Most studies focused on individual characteristics of respondents, neglecting the potential contribution of health care professionals to the phenomenon of psychotropic drug use among seniors.
Primary small-cell neuroendocrine carcinoma of the duodenum – a case report and review of literature
Authors: Sata Naohiro , Tsukahara Munetoshi , Koizumi Masaru , Yoshizawa Koji , Kurihara Katsumi , Nagai Hideo , Someya Tsutomu , Saito Ken 
Published: August 2004

Abstract
Background
Small-cell neuroendocrine carcinoma in the duodenum is an extremely rare neoplasm with poor prognosis.

Case presentation
A 57-year-old man presented with sudden onset gastrointestinal bleeding and fainting attacks. Duodenoscopy and hypotonic duodenography revealed a 3 × 3 cm protruding tumor with ulcerations situated opposite the ampulla of Vater in the second part of the duodenum. Local excision of the tumor was performed, followed by adjuvant chemotherapy with 5-fluoro uracil and leucovorin. Examination of the tumor by immunohistochemistry and electron microscopy indicated it to be neuroendocrine in nature, expressing synaptophysin and AE1/AE3, and containing dense core granules. The patient showed no sign of recurrence and has been disease-free for more than 48 months after surgery.

Conclusions
Most cases of small-cell neuroendocrine carcinoma in the duodenum show rapid progression of the disease, and even radical surgery with or without chemotherapy do not prevent death. We report a rare subtype of small-cell neuroendocrine carcinoma. This subtype appears to have a much better prognosis, and may be amenable to local excision, if the lesion is away from the ampulla of Vater.
Induction and antimicrobial activity of platelet basic protein derivatives in human monocytes
Authors: Schaffner Andreas , King Charles C , Schaer Dominik , Guiney Donald G 
Published: August 2004

AbstractThe antimicrobial activity of a number of chemokines has recently come into focus of research about innate immunity. We have previously shown that platelet basic protein (PBP), which gives rise to several antimicrobial peptides of platelets, is also expressed in human monocytes. In the present studies, we show that exposure of human monocytes to bacteria or microbial components (lipopolysaccharide and zymosan) induces a several-fold greater expression of derivates of PBP. Also, activation of proteinase-activated receptors (PARs) by thrombin or the synthetic peptide ligand SFLLRN of PAR-1 significantly increased PBP expression, presumably on the transcriptional level, as evidenced by higher mRNA levels. Derivates of PBP appeared to reach phago-lysosomes, as higher concentration was found in latex phagosomes isolated by a flotation method. By the gel-overlay technique, two bactericidal derivatives of PBP could be visualized, which were immunoreactive with anti-PBP antibody in Western blots. By matrix-assisted laser desorption/ionization time of flight and surface-enhanced laser desorption and ionization techniques, it was confirmed that the bands corresponded to PBP derivates. After immunofixation with a monoclonal antibody to PBP, the major peptide in zymosan-stimulated monocytes was identified to correspond by molecular weight to connective tissue-activating peptide III, which has been reported to be a major antimicrobial PBP derivate also in platelets. Our observations indicate that PBP and its derivates are constituents of the antimicrobial arsenal of human monocytes. Their increased expression after exposure to microorganisms allows a rapid host response to pathogens.
Dendritic cells retrovirally overexpressing IL-12 induce strong Th1 responses to inhaled antigen in the lung but fail to revert established Th2 sensitization
Authors: Kuipers Harmjan , Heirman Carlo , Hijdra Daniëlle , Muskens Femke , Willart Monique , van Meirvenne Sonja , Thielemans Kris , Hoogsteden Henk C , Lambrecht Bart N 
Published: August 2004

AbstractIt has been postulated that low-level interleukin (IL)-12 production of antigen-presenting cells is associated with the risk of developing atopic asthma. To study the relationship between IL-12 production capacity of dendritic cells (DCs) and development of T helper type 2 (Th2) responses in the lung, we genetically engineered DCs to constutively overexpress bioactive IL-12. Retrovirally mediated overexpression of IL-12 in DCs strongly polarized naïve ovalbumin (OVA)-specific CD4+ T cells toward Th1 effector cells in vitro. After intratracheal injection, OVA-pulsed IL-12-overexpressing DCs failed to induce Th2 responses in vivo and no longer primed mice for Th2-dependent eosinophilic airway inflammation upon OVA aerosol challenge, readily observed in mice immunized with sham-transfected, OVA-pulsed DCs. Analysis of a panel of cytokines and chemokines in the lung demonstrated that the lack of Th2 sensitization was accompanied by increased production of the Th1 cytokine interferon-γ (IFN-γ), chemokines induced by IFN-γ, and the immunoregulatory cytokine IL-10. When Th2 priming was induced using OVA/alum prior to intratracheal DC administration, DCs constitutively expressing IL-12 were no longer capable of preventing eosinophilic airway inflammation and even enhanced it. These data show directly that high-level expression of IL-12 in DCs prevents the development of Th2 sensitization. Enhancing IL-12 production in DCs should be seen as a primary prevention strategy for atopic disorders. Enhancing IL-12 production in DCs is less likely to be of benefit in already Th2-sensitized individuals.
Respiratory Stimulant Use in Chronic Obstructive Pulmonary Disease
Authors: Bales Melissa J , Timpe Erin M 
Published: August 2004

OBJECTIVE To evaluate the use of respiratory stimulants in chronic obstructive pulmonary disease (COPD). DATA SOURCES MEDLINE (1966–July 2003) and EMBASE (1980–3rd quarter 2003) were searched using the search terms medroxyprogesterone acetate, acetazolamide, chronic obstructive pulmonary disease, and chronic obstructive lung disease. DATA SYNTHESIS Trials are reviewed evaluating ventilatory parameters with acetazolamide and/or medroxyprogesterone in patients with COPD. All studies found improvements in ventilatory parameters, but failed to demonstrate improvements in survival or quality of life. CONCLUSIONS Significant improvement in arterial blood gas and ventilatory parameters was reported in COPD patients after acetazolamide and medroxyprogesterone treatment; however, with no improvement in survival or quality of life, the place of these drugs in therapy remains unknown.
Valproic Acid—Induced Hyperammonemia and Thrombocytopenia in an Elderly Woman
Authors: Mallet Louise , Babin Steve , Morais José A 
Published: August 2004

OBJECTIVE To describe a case of oral valproic acid—induced hyperammonemia and thrombocytopenia in an elderly patient. CASE SUMMARY A 76-year-old white woman presented to the emergency department with generalized weakness, confusion, nausea, and vomiting. She was taking sodium divalproex 750 mg 3 times daily, with valproic acid concentration 144 mg/L. She was admitted to the medical ward. The dose of sodium divalproex was decreased and discontinued. During her hospital stay, the woman's ammonia level rose to 211 μg/dL despite a normal valproic acid concentration. She was confused, somnolent, and had decreased mobility. Her platelet count decreased from 133 to 86 × 103/mm 3 . Gabapentin was prescribed for seizure control. The patient's mental status, ammonia level, and platelet count returned to baseline following discontinuation of valproic acid. DISCUSSION It has been reported that valproic acid can interfere with the enzyme carbamoylphosphate synthetase, which is responsible for incorporating ammonia into the urea cycle. It has also been reported that valproic acid can increase the transport of glutamine across the mitochondrial membrane in the kidney, thereby increasing the production of ammonia. The etiology of valproic acid—induced thrombocytopenia has not been elucidated. Using the Naranjo probability scale, a probable relationship between hyperammonemia and valproic acid and a possible relationship between thrombocytopenia and valproic acid were determined. CONCLUSIONS Valproic acid can be associated with hyperammonemia and thrombocytopenia. Clinicians should be aware of changes in patients' cognitive and functional capacity, especially elderly patients on sodium divalproex.