bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular Changes of Reissner's Membrane in Meniere's Disease: Human Temporal Bone Study
Authors: Cureoglu Sebahattin , Schachern Patricia A. , Paul Saurav , Paparella Michael M. , Singh Rajesh K. 
Published: January 2004

ObjectiveTo study the cellular characteristics of Relssner's membrane (RM) in temporal bones (TBs) from patients with endolymphatic hydrops with symptoms of Menlere's disease (EH/+MD) and TBs with endolymphatic hydrops without symptoms of Meniere's disease (EH/‐MD) in an effort to understand the role of endolymphatic hydrops in MD symptoms.Study DesignComparative study of human TB histopathology.Methods and MaterialsEpithelial and mesothelial cellularity of RM from control TBs, TBs from patients with EH/+MD, and TBs from patients with EH/‐MD were compared. The cellularity of epithelial and mesothelial cell nuclel (defined as number of cells/ 100 μm width of RM) were counted along the width of RM. The width of RM was measured from the vestibular crest of the spiral ligament to the limbus spiralis.ResultsThe cellular densities of epithelial cells in the basal and middle turns of RM were significantly higher in the EH/+MD and EH/‐MD groups compared with “controls.” There was no difference in epithelial cellularity between EH/+MD and EH/‐MD. There was a decrease in the number of mesothelial cells of RM in the basal turn in EH/+MD and EH/‐MD groups (statistically significant only in EH/+MD group) when compared with controls. The number of mesothelial cells of RM in the middle turn in EH/+MD and EH/‐MD groups were significantly decreased compared with normals.DiscussionSimilar findings in cellularity of RM in temporal bones with EH/+MD and EH/‐MD suggest that pathophysiologic mechanisms other than hydrops may be responsible for symptoms in Meniere's disease.
Sale of monopoly information and behavior of rivaling clients: A theoretical perspective
Authors: Chang Chun‐Hao , Prakash Arun J. , Yeh Shu 
Published: January 2004

AbstractThis paper studies a three‐stage Bayesian–Cournot game where rivaling firms sign contracts with an information monopoly to purchase proprietary information. The rivaling firms use the external information to create competitive advantage over one another. Knowing the rivalry among its clients, the information monopoly can exploit them by playing one client against another. The information‐selling strategy depends on the clients' in‐house information technology, the uncertainty of the economic environment, and the number of potential clients. The existence of an information market makes rivaling producers worse off and consumers better off. It is possible that the service of the information monopoly is a private good but a social bad.
The Wiskott–Aldrich syndrome protein: forging the link between actin and cell activation
Authors: Badour Karen , Zhang Jinyi , Siminovitch Katherine A. 
Published: January 2004

Summary:The Wiskott–Aldrich syndrome protein (WASp) has emerged as a central player in the regulation of actin remodeling in T cells. The unique domain structure of WASp and other WASp family members enables these proteins to associate with a myriad of signaling effectors and to thereby regulate the coupling of T cell antigen receptor (TCR) engagement to both cytoskeletal rearrangement and transcriptional activation. This review focuses on these biochemical properties of WASp and also on the mechanisms whereby WASp interactions with its cognate ligands influence T cell activation. Because of its capacity to shift intracellular location and thereby dictate both the timing and the spatial distribution of actin polymerization following cell stimulation, WASp is well positioned to play major regulatory roles in directing a wide range of cellular processes and signaling pathways. Further dissection of the functional and biochemical properties of WASp therefore represents a promising avenue towards defining the molecular mechanisms that convey TCR stimulatory signals to the actin cytoskeleton and integrate cytoskeletal and other signaling systems so as to evoke a biological response.
Vav1: a key signal transducer downstream of the TCR
Authors: Tybulewicz Victor L. J. , Ardouin Laurence , Prisco Antonella , Reynolds Lucinda F. 
Published: January 2004

Summary: Vav1 is a 95‐kDa protein expressed in all hemopoietic cells that becomes rapidly tyrosine phosphorylated following T cell antigen receptor (TCR) stimulation. Vav1 contains multiple domains characteristic of signal transducing proteins, including a Dbl homology domain, a hallmark of a guanine nucleotide exchange factor (GEF) for Rho‐family GTPases. Indeed Vav1 is a GEF for Rac1, Rac2 and RhoG, and it is activated following tyrosine phosphorylation. Generation of mice deficient in Vav1 has shown that it plays an important role in selection events within the thymus, including both positive and negative selection, consistent with Vav1 transducing TCR signals required to drive these processes. Furthermore, Vav1‐deficient T cells are defective in TCR‐induced proliferation and cytokine synthesis.Analysis of TCR signaling pathways in Vav1‐deficient T cells and thymocytes has shown that Vav1 is required to transduce signals to the activation of a calcium flux, extracellular signal‐regulated kinase (ERK) and the nuclear factor κB (NF‐κB) transcription factor. Vav1 has also been shown to control the activation of phospholipase Cγ1 (PLCγ1) via both phosphoinositide‐3‐kinase (PI3K)‐dependent and ‐independent pathways. Finally, Vav1 has been shown to transduce TCR signals to some but not all cytoskeleton‐dependent pathways. In particular, Vav1 is required for efficient TCR‐induced conjugate formation with antigen presenting cells (APCs), activation of the integrin leukocyte function‐associated antigen‐1 (LFA‐1) and cell polarization.
Molecular modifiers of T cell antigen receptor triggering threshold: the mechanism of CD28 costimulatory receptor
Authors: Acuto Oreste , Mise‐Omata Setsuko , Mangino Giorgio , Michel Frédérique 
Published: January 2004

Summary: CD28 was thought to represent a prototypic membrane receptor responsible for delivering the classically defined ‘second signal’ needed to avoid T cell paralysis when recognizing antigen presented by appropriate antigen presenting cells (APCs). Almost two decades after its molecular identification, the mechanism by which this ‘second receptor’ facilitates clonal expansion and differentiation upon antigen encounter is still not fully elucidated. There may be at least two reasons for this partially gray picture: the use of nonphysiological experimental conditions to study it and the fact that the action of CD28 may be partly masked by the presence of additional T cell surface receptors that also provide some costimulatory signals, although not equivalent to the one delivered through CD28. Thus, instead of aging, the study of CD28 is still a topical subject. What is appearing through work of recent years is that far from being purely qualitative, the CD28 signal provides a key quantitative contribution to potently boost the T cell antigen receptor (TCR) signal. In other words, CD28 is in part a signaling ‘sosia’ of the TCR. Also, it is clear now that CD28 operates via multiple molecular effects. Still, what we do not understand is the ‘qualitative’ part of this signal, perhaps due to lack of identification of unique signaling components and/or pathways activated by CD28 only. Here we review a series of recent findings pointing towards novel avenues to better understand the molecular basis of CD28 function.
Additional cytogenetic abnormalities in adults with Philadelphia chromosome‐positive acute lymphoblastic leukaemia: a study of the Cancer and Leukaemia Group B
Authors: Wetzler Meir , Dodge Richard K. , Mrózek Krzysztof , Stewart Carleton C. , Carroll Andrew J. , Tantravahi Ramana , Vardiman James W. , Larson Richard A. , Bloomfield Clara D. 
Published: January 2004

SummaryWe analysed the nature and prognostic significance of secondary cytogenetic changes in 111 newly diagnosed adults with acute lymphoblastic leukaemia (ALL) and t(9;22)(q34;q11.2) or its variants. Secondary aberrations were seen in 75 (68%) patients. They included, in order of descending frequency: +der(22)t(9;22), +21, abnormalities of 9p, high hyperdiploidy (>50 chromosomes), +8, −7, +X and abnormalities resulting in loss of material from 8p, gain of 8q, gain of 1q and loss of 7p. Eighty patients (72%) had ≥1 normal metaphase in their karyotype. There were four balanced and 12 unbalanced translocations previously unreported in ALL with t(9;22). The t(2;7)(p11;p13) and der(18)t(8;18)(q11.2;p11.2) were seen in two cases each, and have never before been reported in haematological malignancy. All but four patients were treated on front‐line Cancer and Leukaemia Group B clinical protocols. The presence of −7 as a sole secondary abnormality was associated with a lower complete remission (CR) rate (P = 0·004), while the presence of ≥3 aberrations was associated with a higher CR rate (P = 0·009) and +der(22)t(9;22) with a higher cumulative incidence of relapse (P = 0·02). It will be of interest to see if newly diagnosed t(9;22)‐positive adult ALL patients with these and other secondary aberrations respond differently to treatment regimens that include imatinib mesylate.
Immunoglobulin heavy chain genes somatic hypermutations and chromosome 11q22‐23 deletion in classic mantle cell lymphoma: a study of the Swiss Group for Clinical Cancer Research
Authors: Bertoni Francesco , Conconi Annarita , Cogliatti Sergio B. , Schmitz Shu‐Fang Hsu , Ghielmini Michele , Cerny Thomas , Fey Martin , Pichert Gabriella , Bertolini Francesco , Ponzoni Maurilio , Baldini Luca , Jones Chris , Auer Rebecca , Zucca Emanuele , Cavalli Franco , Cotter Finbarr E. ,   for the Swiss Group for Clinical Cancer Research
Published: January 2004

SummaryMantle cell lymphoma (MCL) shares immunophenotypic and karyotypic features with chronic lymphocytic leukaemia. The latter comprises two distinct entities with prognosis dependent upon immunoglobulin heavy chain (IgH) gene mutational status and the presence of 11q deletion. We evaluated the relevance of IgH gene mutational status, IgV gene family usage and presence of 11q deletion in a series of 42 histologically reviewed classical MCL cases to determine the prognostic impact. VH3 was the most common VH family, with VH3‐21 being the most frequent individual VH gene. Approximately 30% of the cases had a IgH somatic mutation rate higher than 2%, but was only higher than 4% in <10% of cases. Half of the cases had deletion of chromosome 11q21‐telomere (11q21‐>ter), with two minimal deleted regions, at 11q22.2 and 11q23.2. There was no association between 11q loss and IgH gene somatic mutation rate; the use of VH3‐21 gene could be associated with a better prognosis.
Increased CD11b neutrophil expression in Budd–Chiari syndrome or portal vein thrombosis secondary to polycythaemia vera
Authors: Alvarez‐Larrán Alberto , García‐Pagán Juan Carlos , Abraldes Juan G. , Arellano Eduardo , Reverter Juan Carlos , Bosch Jaume , Cervantes Francisco 
Published: January 2004

SummaryBudd–Chiari syndrome and portal vein thrombosis (BCS/PVT) are frequently associated with polycythaemia vera (PV). In an attempt to elucidate the mechanisms of BCS/PVT secondary to PV (T‐PV), CD11b neutrophil expression, neutrophil oxidative burst and platelet–neutrophil complexes (PNC) were assessed in 17 such patients. Three groups served as controls: BCS/PVT not secondary to PV (T‐nPV; n = 20), PV without thrombosis (PV‐nT; n = 16), and healthy controls (HC; n = 20). Baseline CD11b expression (in mean fluorescence intensity units) was 101 [95% confidence interval (CI): 79–128] in T‐PV patients, versus 25 (95% CI: 18–35) in T‐nPV, 59 (95% CI: 43–80) in PV‐nT, and 34 (95% CI: 25–48) in HC (P < 0·001). After N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine activation, T‐PV patients also showed higher CD11b values: 190 (95% CI: 151–238), versus 55 (95% CI: 41–72) in T‐nPV, 111 (95% CI: 81–153) in PV‐nT, and 77 (95% CI: 63–95) in HC (P < 0·001). In BCS/PVT, CD11b neutrophil expression had 90% specificity and 100% sensitivity for the association with PV. Finally, PV patients had higher oxidative burst and PNC than T‐nPV patients or HC (P < 0·05). These results support a role for neutrophils in BCS/PVT secondary to PV and indicate that neutrophil CD11b expression could be of use for PV screening in BCS/PVT patients.
Standardization of the endogenous thrombin potential measurement: how to minimize the effect of residual platelets in stored plasma
Authors: Chantarangkul Veena , Clerici Marigrazia , Bressi Caterina , Tripodi Armando 
Published: January 2004

SummaryPlatelet contamination in stored plasma may affect coagulation assays, including the endogenous thrombin potential (ETP), which has been proposed for the investigation of hyper‐ and hypo‐coagulability. The current recommendation of filtering plasma before freezing cannot be always met. This study provides evidence that filtering frozen plasma after thawing, prior to testing, may help to eliminate the unwanted effect of residual platelets on the ETP. This may have important implications in future studies, as the ETP could be determined with plasma that have been collected without precautions relating to platelet contamination, as is the case for plasmas collected in epidemiological studies.
Magnetic resonance screening of iron status in transfusion‐dependent β‐thalassaemia patients
Authors: Ooi G. C. , Khong P. L. , Chan G. C. F. , Chan K. N. , Chan K. L. , Lam W. , Ng I. , Ha S. Y. 
Published: January 2004

SummaryThe clinical utility of dual sequence (T1‐ and T2‐weighted) magnetic resonance (MR) imaging in estimating liver iron concentration (LIC) in 32 transfusion‐dependent β‐thalassaemia major (24 females; age 18·5±5·9 years) patients on desferrioxamine was evaluated. Signal intensity ratios (SIR) between liver, spleen and pancreas to psoas muscle were determined on both sequences. Relationships between clinical and MR parameters, and accuracy of SIR thresholds in determining adequacy of chelation from LIC were analysed. Liver T1‐ and T2‐SIR were related to LIC (P < 0·001). T1‐SIR < 0·60 predicted severe iron overload (LIC > 15 mg/g) with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100%, 87%, 33% and 100% respectively. T2‐SIR < 0·1 yielded 100% sensitivity, 93% specificity, 50% PPV and 100% NPV. T1‐SIR ≥ 1·1 predicted LIC < 7 mg/g with 69% sensitivity, 88% specificity, 85% PPV and 74% NPV. T2‐SIR ≥ 0·20 yielded 56·5% sensitivity, 94% specificity, 90% PPV and 71% NPV. LIC correlated with liver T1‐SIR, liver T2‐SIR and serum ferritin (r = −0·76, −0·65, 0·47, respectively; P < 0·01). Serum ferritin was inversely related to liver T1‐SIR, liver T2‐SIR and spleen T2‐SIR (r = −0·35, −0·43, −0·40, respectively; P < 0·05). Mean total transfusion burden was not related to any MR parameter. Although neither MR sequence was a highly accurate predictor of LIC, SIR thresholds are useful to determine presence of iron overload and adequacy of chelation treatment.
Platelet microparticles induce angiogenesis in vitro
Authors: Kim Hyun Kyung , Song Kyung Soon , Chung Jun‐Ho , Lee Kyoung Rhan , Lee Se‐Na 
Published: January 2004

SummaryPlatelet microparticles (PMP) are endogenous substances generated during the coagulation process in a hypercoagulable state. This study demonstrated that PMP promote the proliferation and survival, migration, and tube formation in human umbilical vein endothelial cells (HUVEC). Heat‐treated PMP did not significantly decrease the angiogenic activity in HUVEC compared with that of the untreated PMP. Meanwhile when PMP were treated with activated charcoal, a procedure known to remove the lipid growth factors, the angiogenic activity was significantly reduced. These results suggest that the lipid component(s) of the PMP may be major active factor(s) and that protein component(s) may be minor contributor(s). PMP were also shown to augment endothelial progenitor cell differentiation in peripheral blood mononuclear cells. In addition, PMP‐stimulated proliferation, chemotaxis and tube formation of the HUVEC was mediated via the Pertussis toxin‐sensitive G protein, extracellular signal‐regulated kinase and the phosphoinositide 3‐kinase pathway. Herein, a new action of PMP was demonstrated to be a potent angiogenic stimulator. It is expected that in pathological states such as a growing tumour, PMP shed from the circulating platelets may reach adequate concentrations and that the elevated levels of PMP could contribute to florid formation of new blood vessels.
Genetic variability of von Willebrand factor and risk of coronary heart disease: the Rotterdam Study
Authors: Van Der Meer Irene M. , Brouwers Geert‐Jan , Bulk Saskia , Leebeek Frank W. G. , Van Der Kuip Deirdre A. M. , Hofman Albert , Witteman Jacqueline C. M. , Gómez García Encarnación B. 
Published: January 2004

SummaryThe von Willebrand factor (VWF) may be causally associated with coronary heart disease (CHD) or merely be a marker of endothelial damage. The G allele of the −1793 C/G promoter polymorphism in the VWF gene has been associated with higher plasma levels of VWF. To investigate whether VWF has a causal role in CHD, we designed a case‐cohort study, including 352 subjects with CHD and a random cohort (n = 736), and prospectively examined the association of the −1793 C/G polymorphism with CHD in subjects with and without advanced atherosclerosis. All subjects were ≤75 years of age and participating in the population‐based Rotterdam Study. Atherosclerosis was assessed by the ankle–arm index. Among subjects with advanced atherosclerosis, heterozygous and homozygous carriers of the G allele had a 3·5 (1·2–10·2) and 1·5 (0·4–5·7) fold increased risk of CHD respectively, compared with C/C homozygotes. The hazard ratio was 2·6 (1·0–6·8) for carriers of at least one copy of the G allele versus non‐carriers. No associations were found in the absence of advanced atherosclerosis. In conclusion, this study suggests that the G allele of the −1793 C/G polymorphism in the VWF gene is associated with an increased risk of CHD, but only in subjects with advanced atherosclerosis.
The effects of selective cytokine inhibitory drugs (CC‐10004 and CC‐1088) on VEGF and IL‐6 expression and apoptosis in myeloma and endothelial cell co‐cultures
Authors: Molostvov G. , Morris A. , Rose P. , Basu S. , Muller G. 
Published: January 2004

SummaryMyeloma cells and human umbilical vein endothelial cells (HUVECs) were co‐cultured to model in vitro the interactions between myeloma and endothelium, and treated with thalidomide and two selective cytokine inhibitory drugs (SelCIDs, phosphodiesterase‐4 inhibitors). Flow cytometry and enzyme‐linked immunosorbent assay were used to assess production of two key cytokines – vascular endothelial growth factor (VEGF) and interleukin‐6 (IL‐6) – and apoptosis in co‐cultured HUVECs and myeloma cells. VEGF was produced by both myeloma cells and HUVECs, while IL‐6 was almost exclusively produced by endothelial cells. In co‐culture, there was significant up‐regulation of VEGF and IL‐6 production compared with the sum of separate myeloma and endothelial cell cultures. SelCIDs markedly inhibited production of both cytokines in co‐cultures, with CC‐10004 being more potent than CC‐1088. In addition, SelCIDs induced myeloma cell apoptosis. Apoptosis in co‐cultured myeloma cells was significantly lower than in those cultured separately, suggesting that co‐culture partially protected myeloma cells from drug‐induced apoptosis. This protective effect was probably due to IL‐6 produced by endothelial cells in co‐culture as addition of anti‐IL‐6 neutralizing antibody, but not anti‐VEGF antibody, abrogated it. In conclusion, SelCIDs can exert their anti‐myeloma activity through two mechanisms, i.e. inhibition of VEGF and IL‐6 production by interacting myeloma and endothelium and induction of myeloma cell apoptosis.
A patient homozygous for a Gly354Cys mutation in factor VII that results in severely impaired secretion of the molecule, but not complete deficiency
Authors: Takamiya Osamu , Hino Kenichiro 
Published: January 2004

SummaryWe investigated the molecular basis of factor VII (FVII) deficiency in a Japanese woman who suffered occasional epistaxis. The patient had low levels of both FVII coagulant activity (FVII:C) and antigen (FVII:Ag) (5·0% and 7·3% of normal controls respectively). DNA sequence analysis of the FVII gene showed that the patient was homozygous for a mutation that resulted in a Cys for Gly354 substitution, a novel missense mutation in the catalytic domain. Haplotype analysis showed that this missense mutation was inherited from her consanguineous parents. Transient expression experiments showed that secreted FVII Cys354, FVII:C and FVII:Ag levels in conditioned media were reduced to 4% and 5%, respectively, of levels secreted from wild‐type FVII. However, the intracellular FVII Cys354 was 67% that of normal recombinant protein. Immunohistochemical analysis showed that intracellular FVII:Ag from FVII 354Cys was present diffusely throughout the cytoplasm. Substitution of FVII 354Gly with amino acids other than Cys (Arg, Asp, Ser and Phe), did not produce a phenotype similar to FVII Cys354Gly. Molecular modelling indicated that FVII Gly354 was located outside the FVII heavy chain, and that Cys135 in the EGF2 domain, Cys262 in the catalytic domain and Cys127 all exist within 10 Å of Gly354. Therefore, we propose that the introduction of an additional free cysteine residue in the FVII molecule results in the formation of illegitimate disulphide bonds and a mis‐folded domain, leading to defective secretion.
Systemic AL amyloidosis due to non‐Hodgkin's lymphoma: an unusual clinicopathologic association
Authors: Cohen A. D. , Zhou P. , Xiao Q. , Fleisher M. , Kalakonda N. , Akhurst T. , Chitale D. A. , Moscowitz C. , Dhodapkar M. V. , Teruya‐Feldstein J. , Filippa D. , Comenzo R. L. 
Published: January 2004

SummarySystemic AL amyloidosis (AL) is a disorder in which light chains form fibrillar deposits, leading to organ dysfunction and death. Rarely, AL has been associated with non‐Hodgkin's lymphoma (NHL), although this association has not been well characterized. We report a series of six patients with AL associated with NHL, primarily lymphoplasmacytic lymphoma. Organ involvement was variable, with frequent bulky lymphadenopathy and visceral cavity deposits, but no cardiac involvement. Positron emission tomography scans were negative. Bone marrow and lymph node biopsies showed a mixed population of CD20+ lymphoid and CD138+ plasma cells. Serum free light chains were elevated, and correlated with response to therapy. Immunoglobulin light chain variable region (Ig VL) germline gene use was typical for AL, reflecting previously observed correlations between germline gene use and organ tropism. Five patients received rituximab‐based therapies with two responses. Two patients underwent autologous stem cell transplantation with one complete haematological response. Four patients survive at 10–132 months from diagnosis. AL with NHL has distinctive clinical features but employs the same Ig VL gene repertoire as AL with clonal plasma cell dyscrasias. Serial serum free light chain levels are useful for tracking response to therapy. Treatments aimed at both lymphoid and plasma cell components appear warranted.