bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tetraspanin superfamily member CD151 regulates outside-in integrin αIIbβ3 signaling and platelet function
Authors: Lau Lai-Man , Wee Janet L. , Wright Mark D. , Moseley Gregory W. , Hogarth P. Mark , Ashman Leonie K. , Jackson Denise E. 
Published: June 2004

AbstractThe tetraspanin family member CD151 forms complexes with integrins and regulates cell adhesion and migration. While CD151 is highly expressed in megakaryocytes and to a lesser extent in platelets, its physiologic role in platelets is unclear. In this study, we investigate the physical and functional importance of CD151 in murine platelets. Immunoprecipitation/Western blot studies reveal a constitutive physical association of CD151 with integrin αIIbβ3 complex under strong detergent conditions. Using CD151-deficient mice, we show that the platelets have impaired “outside-in” integrin αIIbβ3 signaling with defective platelet aggregation responses to protease-activated receptor 4 (PAR-4) agonist peptide, collagen, and adenosine diphosphate (ADP); impaired platelet spreading on fibrinogen; and delayed kinetics of clot retraction in vitro. This functional integrin αIIbβ3 defect could not be attributed to altered expression of integrin αIIbβ3. CD151–/– platelets displayed normal platelet alpha granule secretion, dense granule secretion, and static platelet adhesion. In addition, CD151–/– platelets displayed normal “inside-out” integrin αIIbβ3 signaling properties as demonstrated by normal agonist-induced binding of soluble fluorescein isothiocyanate (FITC)–fibrinogen, JON/A antibody binding, and increases in cytosolic-free calcium and inositol 1,4,5 triphosphate (IP3) levels. This study provides the first direct evidence that CD151 is essential for normal platelet function and that disruption of CD151 induced a moderate outside-in integrin αIIbβ3 signaling defect.
An association of candidate gene haplotypes and bleeding severity in von Willebrand disease (VWD) type 1 pedigrees
Authors: Kunicki Thomas J. , Federici Augusto B. , Salomon Daniel R. , Koziol James A. , Head Steven R. , Mondala Tony S. , Chismar Jeffrey D. , Baronciani Luciano , Canciani Maria Teresa , Peake Ian R. 
Published: June 2004

Abstractvon Willebrand disease (VWD) type 1 is difficult to diagnose because of bleeding variability and low heritability of von Willebrand factor (VWF) levels. We compared a bleeding severity score and bleeding times to candidate gene haplotypes within pedigrees of 14 index cases, using a covariance components model for multivariate traits (Mendel: QTL Association). These pedigrees included 13 affected and 40 unaffected relatives, as defined by plasma ristocetin cofactor (VWF:RCo) levels. The bleeding severity score was derived from a detailed history. Donors were genotyped using a primer extension method, and 9 candidate genes were selected for analysis. VWF:RCo levels had the strongest influence on bleeding severity score and bleeding time. ITGA2 haplotype 2 (807C) and ITGA2B haplotype 1 (Ile843) were each associated with increased bleeding severity scores (P &lt; .01 and P &lt; .01, respectively). GP6 haplotype b (Pro219) was also associated with increased scores (P = .03) after adjustment for donor age. No association was observed with 6 other candidate genes, GP1BA, ITGB3, VWF, FGB, IL6, or TXA2R. Increased plasma VWF:Ag levels were associated with VWF haplotype 1 (–1793G; P = .02). These results establish that genetic differences in the adhesion receptor subunits α2, αIIb, and GPVI can influence the phenotype of VWD type 1.
Cyclin D1 activation in B-cell malignancy: association with changes in histone acetylation, DNA methylation, and RNA polymerase II binding to both promoter and distal sequences
Authors: Liu Hui , Wang Jin , Epner Elliot M. 
Published: June 2004

AbstractCyclin D1 expression is deregulated by chromosome translocation in mantle cell lymphoma and a subset of multiple myeloma. The molecular mechanisms involved in long-distance gene deregulation remain obscure, although changes in acetylated histones and methylated CpG dinucleotides may be important. The patterns of DNA methylation and histone acetylation were determined at the cyclin D1 locus on chromosome 11q13 in B-cell malignancies. The cyclin D1 promoter was hypomethylated and hyperacetylated in expressing cell lines and patient samples, and methylated and hypoacetylated in nonexpressing cell lines. Domains of hyperacetylated histones and hypomethylated DNA extended over 120 kb upstream of the cyclin D1 gene. Interestingly, hypomethylated DNA and hyperacetylated histones were also located at the cyclin D1 promoter but not the upstream major translocation cluster region in cyclin D1-nonexpressing, nontumorigenic B and T cells. RNA polymerase II binding was demonstrated both at the cyclin D1 promoter and 3′ immunoglobulin heavy-chain regulatory regions only in malignant B-cell lines with deregulated cyclin D1 expression. Our results suggest a model where RNA polymerase II bound at IgH regulatory sequences can activate the cyclin D1 promoter by either long-range polymerase transfer or tracking.
From the bench to the bedside: ways to improve rituximab efficacy
Authors: Cartron Guillaume , Watier Hervé , Golay Josée , Solal-Celigny Philippe 
Published: June 2004

AbstractRituximab (MabThera, Rituxan) is a chimeric IgG1 monoclonal antibody that specifically targets the CD20 surface antigen expressed on normal and neoplastic B-lymphoid cells. Rituximab is currently used in the treatment of both follicular and aggressive B-cell non-Hodgkin lymphomas. Despite its demonstrated clinical effectiveness, its in vivo mechanisms of action remain unknown and could differ by subtype of lymphoma. Rituximab has been shown to induce apoptosis, complement-mediated lysis, and antibody-dependent cellular cytotoxicity in vitro, and some evidence points toward an involvement of these mechanisms in vivo. Rituximab also has a delayed therapeutic effect as well as a potential “vaccinal” effect. Here, we review the current understanding of the mechanism of action of rituximab and discuss approaches that could increase its clinical activity. A better understanding of how rituximab acts in vivo should make it possible to develop new and more effective therapeutic strategies. (Blood. 2004;104:2635-2642)
In vitro and in vivo evaluation of a new active heat moisture exchanger
Authors: Chiumello Davide , Pelosi Paolo , Park Gilbert , Candiani Andrea , Bottino Nicola , Storelli Ezio , Severgnini Paolo , D'Onofrio Dunia , Gattinoni Luciano , Chiaranda Massimo 
Published: June 2004

Abstract
Introduction
In order to improve the efficiency of heat moisture exchangers (HMEs), new hybrid humidifiers (active HMEs) that add water and heat to HMEs have been developed. In this study we evaluated the efficiency, both in vitro and in vivo, of a new active HME (the Performer; StarMed, Mirandola, Italy) as compared with that of existing HMEs (Hygroster and Hygrobac; Mallinckrodt, Mirandola, Italy).

Methods
We tested the efficiency by measuring the temperature and absolute humidity (AH) in vitro using a test lung ventilated at three levels of minute ventilation (5, 10 and 15 l/min) and at two tidal volumes (0.5 and 1 l), and in vivo in 42 patients with acute lung injury (arterial oxygen tension/fractional inspired oxygen ratio 283 ± 72 mmHg). We also evaluated the efficiency in vivo after 12 hours.

Results
In vitro, passive Performer and Hygrobac had higher airway temperature and AH (29.2 ± 0.7°C and 29.2 ± 0.5°C, [P < 0.05]; AH: 28.9 ± 1.6 mgH2O/l and 28.1 ± 0.8 mgH2O/l, [P < 0.05]) than did Hygroster (airway temperature: 28.1 ± 0.3°C [P < 0.05]; AH: 27 ± 1.2 mgH2O/l [P < 0.05]). Both devices suffered a loss of efficiency at the highest minute ventilation and tidal volume, and at the lowest minute ventilation. Active Performer had higher airway temperature and AH (31.9 ± 0.3°C and 34.3 ± 0.6 mgH2O/l; [P < 0.05]) than did Hygrobac and Hygroster, and was not influenced by minute ventilation or tidal volume. In vivo, the efficiency of passive Performer was similar to that of Hygrobac but better than Hygroster, whereas Active Performer was better than both. The active Performer exhibited good efficiency when used for up to 12 hours in vivo.

Conclusion
This study showed that active Performer may provide adequate conditioning of inspired gases, both as a passive and as an active device.
Direct-to-consumer advertising of psychotropics
Authors: Gilbody Simon , Wilson Paul , Watt Ian 
Published: June 2004

‘Advertising may be described as the science of arresting the human intelligence long enough to get money from it’ (Leacock, 1924).Until recently, the main targets of pharmaceutical advertisements were clinicians and the major vehicles for ‘educational promotion’ were advertisements in academic and professional journals and visits and gifts from pharmaceutical representatives. All is now changed and patients have become legitimate targets of advertising. Direct-to-consumer advertising represents a new and expanding area of pharmaceutical promotion that harnesses the mass media.
Cumulative incidence of mental disorders among offspring of mothers with psychotic disorder
Authors: Niemi Laura T. , Suvisaari Jaana M. , Haukka Jari K. , Wrede Gunnel , Lönnqvist Jouko K. 
Published: June 2004

BackgroundThe Helsinki High-Risk Study follows up all women born between 1916 and 1948 and treated for schizophrenia-spectrum disorders in psychiatric hospitals in Helsinki, their offspring born between 1960 and 1964, and controls.AimsTo determine the cumulative incidence of adulthood Axis I disorders among offspring.MethodUsing all hospital and out-patient treatment records we rediagnosed parents and offspring according to DSM– IV-TR criteria. Offspring were grouped by mother's diagnosis (schizophrenia n = 104, schizoaffective disorder n=20, other schizophrenia-spectrum disorder n=30, and affective disorder n=25) and compared with a control group (n = 176). The cumulative incidences of Axis I disorders among offspring were calculated.ResultsThe cumulative incidences of any psychotic disorder were 13.5%, 10.0%, 10.0%, 4.0% and 1.1% among offspring of mothers with schizophrenia, schizo-affective disorder, other schizophrenia-spectrum disorders, affective disorders and controls, respectively. The corresponding figures for schizophrenia were 6.7%, 5.0%, 6.7%, 0% and 0.6%, and for any mental disorder 23.1%, 20.0%, 20.0%, 12.0% and 6.9%.ConclusionsOffspring of mothers with a psychotic disorder have heightened risk of developing a wide range of severe mental disorders.
Explanatory models of illness in schizophrenia: Comparison of four ethnic groups
Authors: McCabe Rosemarie , Priebe Stefan 
Published: June 2004

BackgroundExplanatory models of illness may differ between ethnic groups and influence treatment satisfaction and compliance.AimsTo compare explanatory models among people with schizophrenia from four cultural backgrounds and explore their relationship with clinical and psychological characteristics.MethodExplanatory models, insight, treatment compliance, health locus of control, quality of life, treatment satisfaction, therapeutic relationships and symptomatology were assessed in UK Whites and Bangladeshis, African-Caribbeans and West Africans.ResultsWhen biological and supernatural causes of illness were compared, Whites cited biological causes more frequently than the three non-White groups, who cited supernatural causes more frequently. When biological and social causes were compared, Whites cited biological causes more frequently than African-Caribbeans and Bangladeshis, who cited social causes more frequently. A biological explanatory model was related to enhanced treatment satisfaction and therapeutic relationships but not treatment compliance.ConclusionsExplanatory models of illness contribute to patient satisfaction with treatment and relationships with clinicians.
Clinical efficacy of computerised cognitive-behavioural therapy for anxiety and depression in primary care: Randomised controlled trial
Authors: Proudfoot Judith , Ryden Clash , Everitt Brian , Shapiro David A. , Goldberg David , Mann Anthony , Tylee Andre , Marks Isaac , Gray Jeffrey A. 
Published: June 2004

BackgroundPreliminary results have demonstrated the clinical efficacy of computerised cognitive-behavioural therapy (CBT) in the treatment of anxiety and depression in primary care.AimsTo determine, in an expanded sample, the dependence of the efficacy of this therapy upon clinical and demographic variables.MethodA sample of 274 patients with anxiety and/or depression were randomly allocated to receive, with or without medication, computerised CBTor treatment as usual, with follow-up assessment at 6 months.ResultsThe computerised therapy improved depression, negative attributional style, work and social adjustment, without interaction with drug treatment, duration of preexisting illness or severity of existing illness. For anxiety and positive attributional style, treatment interacted with severity such that computerised therapy did better than usual treatment for more disturbed patients. Computerised therapy also led to greater satisfaction with treatment.ConclusionsComputer-delivered CBT is a widely applicable treatment for anxiety and/or depression in general practice.
Repetition of deliberate self-harm and subsequent suicide risk: Long-term follow-up study of 11 583 patients
Authors: Zahl Daniel Louis , Hawton Keith 
Published: June 2004

BackgroundRepetition of deliberate self-harm (DSH) is a risk factor for suicide. Little information is available on the risk for specific groups of people who deliberately harm themselves repeatedly.AimsTo investigate the long-term risk of suicide associated with repetition of DSH by gender, age and frequency of repetition.MethodA mortality follow-up study to the year 2000 was conducted on 11583 people who presented to the general hospital in Oxford between 1978 and 1997. Repetition of DSH was determined from reported episodes prior to the index episode and episodes presenting to the same hospital during the follow-up period. Deaths were identified through national registers.ResultsThirty-nine percent of patients repeated the DSH. They were at greater relative risk of suicide than the single-episode DSH group (2.24; 95% CI 1.77–2.84). The relative risk of suicide in the repeated DSH group compared with the single-episode DSH group was greater in females (3.5; 95% C11.3–2.4) than males (1.8; 95% C1 2.3–5.3) and was inversely related to age (up to 54 years). Suicide risk increased further with multiple repeat episodes of DSH in females.ConclusionsRepetition of DSH is associated with an increased risk of suicide in males and females. Repetition may be a better indicator of risk in females, especially young females.
Nucleolar localization and mobility analysis of the NF-κB repressing factor NRF
Authors: Niedick Ina , Froese Natali , Oumard André , Mueller Peter P. , Nourbakhsh Mahtab , Hauser Hansjörg , Köster Mario 
Published: June 2004

NF-κB plays a central role in mediating pathogen and cytokine-stimulated gene transcription. NF-κB repressing factor (NRF) has been shown to interact with specific negative regulatory DNA elements (NRE) to mediate transcriptional repression by inhibition of the NF-κB activity at certain promoters. mRNA ablation experiments demonstrated that the trans-acting NRF protein is involved in constitutive but not post-stimulated silencing of IFN-β, IL-8 and iNOS genes by binding to cis-acting NRE elements in their promoters.
We have examined the subcellular localization and mobility of the NRF protein. Since neither tagging nor overexpression perturbs NRF localization the GFP-tagged protein was used for detailed localization and mobility studies. Owing to an N-terminal nuclear localization sequence, all NRF fragments that contain this signal show a constitutive nuclear accumulation. C-terminal NRF fragments also localize to the nucleus although no canonical NLS motifs were detected. Full-length NRF is highly enriched in nucleoli and only a small fraction of NRF is found in the nucleoplasm and cytoplasm. This relationship was found to be independent of the protein expression rate. FRAP analysis proved to be a sensitive method to determine protein mobility and made it possible to differentiate between the NRF protein fragments. Nucleolar localization correlated inversely with mobility. The data demonstrate that a series of neighboring fragments in a large central domain of the protein contribute to the strong nucleolar affinity. These properties were not altered by viral infection or LPS treatment. Several sequence motifs for RNA binding were predicted by computer-mediated databank searches. We found that NRF binds to double stranded RNA (dsRNA). This property mapped to several NRF fragments which correlate with the nucleolar affinity domain. Since treatment with actinomycin D releases NRF from nucleoli the identified RNA binding motifs might act as nucleolar localization signals.
Differentiation of Acute Myeloid Leukemia from B- and T-Lineage Acute Lymphoid Leukemias by Real-Time Quantitative Reverse Transcription-PCR of Lineage Marker mRNAs
Authors: Saussoy Pascale , Vaerman Jean-Luc , Straetmans Nicole , Deneys Véronique , Cornu Guy , Ferrant Augustin , Latinne Dominique 
Published: June 2004

AbstractBackground: Flow cytometry of lineage markers is useful in the classification of leukemias. Our aim was to assess whether the study of lineage genes at the RNA level would enable differentiation of acute myeloid leukemias (AMLs) from B-and T-lineage acute lymphoid leukemias (ALLs).Methods: We measured mRNA of four lineage markers [CD19, CD79a, CD3e, and myeloperoxidase (MPO)] by reverse transcription followed by real-time quantitative (RTQ)-PCR. We investigated 72 acute leukemias (40 AMLs with 23–93% blast cells plus 27 B-lineage ALLs and 5 T-lineage ALLs) defined by morphologic criteria at diagnosis. RTQ-PCR analysis was performed on bone marrow without cell sorting. The expression of each gene was calculated as the difference in the threshold cycle [ΔCT; CT value of target gene minus CT value of housekeeping gene (Abelson)].Results: Three patterns of expression were detected. In the first, CD19, CD79a, and MPO mRNAs were less abundant than CD3e. In the second pattern, MPO mRNA was more abundant than the other three mRNAs. In the third, CD19 or CD79a was more highly expressed than CD3e and MPO. The three patterns corresponded to T-ALL, AML, and B-ALL, respectively. The use of cutoffs to establish qualitatively the pattern of coexpression of the four lineage markers provided the same information as the comparison among the four ΔCT values. Prospective use of the scoring system correctly classified each of 13 additional cases (8 AML, 4 B-lineage ALL, and 1 T-lineage ALL).Conclusion: Study of lineage markers at diagnosis by RTQ-PCR allows differentiation of AML from B-ALL or T-ALL without cell sorting, even when the bone marrow contains few blast cells.
Genotyping of Single-Nucleotide Polymorphisms by High-Resolution Melting of Small Amplicons
Authors: Liew Michael , Pryor Robert , Palais Robert , Meadows Cindy , Erali Maria , Lyon Elaine , Wittwer Carl 
Published: June 2004

AbstractBackground: High-resolution melting of PCR amplicons with the DNA dye LCGreen™ I was recently introduced as a homogeneous, closed-tube method of genotyping that does not require probes or real-time PCR. We adapted this system to genotype single-nucleotide polymorphisms (SNPs) after rapid-cycle PCR (12 min) of small amplicons (≤50 bp).Methods: Engineered plasmids were used to study all possible SNP base changes. In addition, clinical protocols for factor V (Leiden) 1691G&gt;A, prothrombin 20210G&gt;A, methylenetetrahydrofolate reductase (MTHFR) 1298A&gt;C, hemochromatosis (HFE) 187C&gt;G, and β-globin (hemoglobin S) 17A&gt;T were developed. LCGreen I was included in the reaction mixture before PCR, and high-resolution melting was obtained within 2 min after amplification.Results: In all cases, heterozygotes were easily identified because heteroduplexes altered the shape of the melting curves. Approximately 84% of human SNPs involve a base exchange between A::T and G::C base pairs, and the homozygotes are easily genotyped by melting temperatures (Tms) that differ by 0.8–1.4 °C. However, in ∼16% of SNPs, the bases only switch strands and preserve the base pair, producing very small Tm differences between homozygotes (&lt;0.4 °C). Although most of these cases can be genotyped by Tm, one-fourth (4% of total SNPs) show nearest-neighbor symmetry, and, as predicted, the homozygotes cannot be resolved from each other. In these cases, adding 15% of a known homozygous genotype to unknown samples allows melting curve separation of all three genotypes. This approach was used for the HFE 187C&gt;G protocol, but, as predicted from the sequence changes, was not needed for the other four clinical protocols.Conclusions: SNP genotyping by high-resolution melting analysis is simple, rapid, and inexpensive, requiring only PCR, a DNA dye, and melting instrumentation. The method is closed-tube, performed without probes or real-time PCR, and can be completed in less than 2 min after completion of PCR.
Food Additives
Authors: Somogyi Laszlo P. 
Published: June 2004

Abstract
Food additives may be looked upon as minor ingredients incorporated into foods to affect their properties in some desired way. Most commonly, the effects desired relate to flavor, texture, color, nutritive value, or stability in storage. Food additives are defined and closely regulated at the national level.
This chapter provides a brief overview of 27 functional food additive categories, excluding bulk ingredients such as flour, sugar, fats, and oils. These categories comprise hundreds of individual compounds, representing the majority of those common us in the food system. Typical food applications of each additive are identified, and the important technical and functional properties are described.
While there are many differences in food tastes and preferences among the global population, the major trends driving the food additive industry appear to be very similar in all regions: concern over food safety, health and nutrition, and desire for convenience.
These trends will expand the use of food additives, especially those of natural origin. The global market for food additives exceeded $20 billion in 2003, and it is expected to increase at an annual rate of 3–3.5% during the next 5 years.
The Topsfield Foundation: Fostering Democratic Community Building Through Face‐to‐Face Dialogue
Authors: Flavin‐McDonald Catherine , Barrett Molly Holme 
Published: June 2004

AbstractThe authors interview Paul Aicher, founder of the Topsfield Foundation, Inc., and Martha McCoy, executive director of the Study Circles Resource Center, about the challenges of creating an effective, replicable model for citizen engagement through communitywide study circle programs.
MRX42: Two linkage intervals, one in the pericentromeric region and one in Xq26, and the impact for carrier risk estimation
Authors: Golla Astrid , Rost Imma , Jedele Kerry Baldwin , Albert Angelika , Murken Jan , Holinski‐Feder Elke 
Published: June 2004

AbstractA nonspecific X‐linked mental retardation (MRX) family is reported with four mild to moderately affected males and no intellectual impairment in their obligate carrier mothers. Linkage analysis obtained the same multipoint lod score of 2.08 for two intervals on the X chromosome already reported to be linked to other MRX and syndromic X‐linked mental retardation (XLMR) families: one pericentromeric and the other at Xq26. Since the responsible gene is not yet characterized, haplotyping is presently the only means available for carrier and prenatal testing for this form of MRX. Carrier risk estimation using pedigree and haplotype data for five females at risk is presented, and the difficulties of prenatal diagnosis given linkage to two different regions is discussed. © 2001 Wiley‐Liss, Inc.