bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligoclonal and polyclonal CD4 and CD8 lymphocytes in aplastic anemia and paroxysmal nocturnal hemoglobinuria measured by Vβ CDR3 spectratyping and flow cytometry
Authors: Risitano Antonio M. , Kook Hoon , Zeng Weihua , Chen Guibin , Young Neal S. , Maciejewski Jaroslaw P. 
Published: October 2002

AbstractWe have hypothesized that in aplastic anemia (AA) the presence of antigen-specific T cells is reflected by their contribution to the expansion of a particular variable beta chain (Vβ) subfamily and also by clonal CDR3 skewing. To determine the role of disease-specific “signature” T-cell clones in AA, we studied preferential Vβ usage by flow cytometry and analyzed Vβ-CDR3 regions for the presence of oligoclonality. We first established the contribution of each Vβ family to the total CD4+ and CD8+ lymphocyte pool; in AA and paroxysmal nocturnal hemoglobinuria, a seemingly random overrepresentation of different Vβ families was observed. On average, we found expansion in 3 (of 22 examined) Vβ families per patient. When the contribution of individual Vβ families to the effector pool was examined, more striking Vβ skewing was found. Vβ-CDR3 size distribution was analyzed for the expanded Vβ families in isolated CD4+ and CD8+ populations; underrepresented Vβ families displayed more pronounced CDR3 skewing. Expanded CD4+Vβ subfamilies showed mostly a polyclonal CDR3 size distribution with only 38% of skewing in expanded Vβ families. In contrast, within overrepresented CD8+Vβ types, marked CDR3 skewing (82%) was seen, consistent with nonrandom expansion of specific CD8+ T-cell clones. No preferential expansion of particular Vβ families was observed, in relation to HLA-type. In patients examined after immunosuppressive therapy, an abnormal Vβ-distribution pattern was retained, but the degree of expansion of individual Vβ was lower. As Vβ skewing may correlate with relative Vβ size, oligoclonality in combination with numerical Vβ expansion can be applied to recognition of disease-specific T-cell receptors.
Myelodysplastic syndrome is not merely “preleukemia”
Authors: Albitar Maher , Manshouri Taghi , Shen Yu , Liu Diane , Beran Miloslav , Kantarjian Hagop M. , Rogers Anna , Jilani Iman , Lin Chung Wu , Pierce Sherry , Freireich Emil J. , Estey Elihu H. 
Published: October 2002

Abstract
Myelodysplastic syndrome (MDS) is a disease characterized by ineffective hematopoiesis. There are significant biologic and clinical differences between MDS and acute myeloid leukemia (AML). We studied a cohort of 802 patients, 279 (35%) with newly diagnosed MDS and 523 (65%) with newly diagnosed AML, and compared clinical and biologic characteristics of the 2 groups. Complete clinical and cytogenetic data were available on all patients, and a subgroup of patients was studied for apoptosis, angiogenesis, proliferation, and growth factors. Our results demonstrate that MDS is a discrete entity that is different from AML and is characterized primarily by increased apoptosis in early and mature hematopoietic cells. Using cell sorting and loss of heterozygosity, we demonstrate that the leukemic cells from MDS patients are capable of differentiation into mature myeloid cells and monocytes. We also demonstrate that there is a significant overlap between AML and MDS when MDS is defined on the basis of an arbitrary percentage of blasts of 20% or 30%. These data suggest that despite similarities between AML and MDS in their responses to treatment and outcomes, MDS is biologically and clinically different from AML and should not be considered an early phase of AML. The data indicate that MDS must be better defined on the basis of its biology rather than the percentage of blasts; further, the data suggest that there is a need to develop therapeutic approaches that specifically address the biologic abnormalities of MDS.
IRTAs: a new family of immunoglobulinlike receptors differentially expressed in B cells
Authors: Miller Ira , Hatzivassiliou Georgia , Cattoretti Giorgio , Mendelsohn Cathy , Dalla-Favera Riccardo 
Published: October 2002

AbstractThe IRTA1 and IRTA2 genes encode immunoglobulinlike cell surface receptors expressed in B cells and involved in chromosome 1q21 translocations in B-cell malignancy. We have now characterized and comparatively analyzed the structure and expression pattern of the entire family of IRTA genes, which includes 5 members contiguously located on chromosome 1q21. The IRTA messenger RNAs are expressed predominantly in the B-cell lineage within discrete B-cell compartments: IRTA1 is specific to the marginal zone, IRTA2 and IRTA3 are found in the germinal center light zone and in intraepithelial and interfollicular regions, and IRTA4 and IRTA5 are expressed predominantly in the mantle zone. All IRTA genes code for transmembrane receptors that are closely related to Fc receptors in their most amino-terminal extracellular domains and that possess cytoplasmic domains containing ITIM (immunotyrosine inhibition motifs)– and, possibly, ITAM (immunotyrosine activation motifs)–like motifs. These structural features suggest that the IRTA receptors may play a role in regulating activation of normal B cells and possibly in the development of neoplasia.
Increased dendritic cell number and function following continuous in vivo infusion of granulocyte macrophage–colony-stimulating factor and interleukin-4
Authors: Basak Saroj K. , Harui Airi , Stolina Marina , Sharma Sherven , Mitani Kohnosuke , Dubinett Steven M. , Roth Michael D. 
Published: October 2002

AbstractDendritic cells (DCs) are rare antigen-presenting cells that play a central role in stimulating immune responses. The combination of recombinant granulocyte macrophage–colony-stimulating factor (rGM-CSF) and recombinant interleukin-4 (rIL-4) provides an important stimulus for generating DCs from murine bone marrow precursors in vitro. Using miniature osmotic pumps, we now demonstrate that continuous infusion of these cytokines for 7 days had a similar effect in vivo, increasing the number and function of splenic DCs. Administration of rGM-CSF/rIL-4 (10 μg/d each) increased the concentration of CD11+ DCs by 2.7-fold and the absolute number of splenic DCs by an average of 5.7-fold. DC number also increased in peripheral blood and lymph nodes. The resultant DCs exhibited a different phenotype and function than those in control mice or mice treated with rGM-CSF alone. rGM-CSF/IL-4 increased both the myeloid (CD11c+/CD11b+) and the lymphoid (CD11c+/CD8α+) subpopulations, whereas rGM-CSF increased only myeloid DCs. DCs were highly concentrated in the T-cell areas of white pulp after rGM-CSF/IL-4 administration, whereas they were diffusely distributed throughout white pulp, marginal zones, and red pulp in mice treated with rGM-CSF alone. rGM-CSF/rIL-4 also significantly increased the expression of major histocompatibility complex (MHC) class I and MHC class II on CD11c+ cells and increased their capacity to take up antigens by macropinocytosis and receptor-mediated endocytosis. Splenic DCs generated in response to rGM-CSF/rIL-4 were functionally immature in terms of allostimulatory activity, but this activity increased after short-term in vitro culture. Systemic treatment with rGM-CSF/rIL-4 enhanced the response to an adenoviral-based vaccine and led to antigen-specific retardation in the growth of established tumor. We conclude that systemic therapy with the combination of rGM-CSF/rIL-4 provides a new approach for generating DCs in vivo.
Spontaneous generation and survival of blood dendritic cells in mononuclear cell culture without exogenous cytokines
Authors: Ho Christopher S. K. , Munster David , Pyke Christopher M. , Hart Derek N. J. , López J. Alejandro 
Published: October 2002

AbstractStudies on purified blood dendritic cells (DCs) are hampered by poor viability in tissue culture. We, therefore, attempted to study some of the interactions/relationships between DCs and other blood cells by culturing unseparated peripheral blood mononuclear cell (PBMC) preparations in vitro. Flow cytometric techniques were used to undertake a phenotypic and functional analysis of DCs within the cultured PBMC population. We discovered that both the CD11c+ and CD11c− CD123hi DC subsets maintained their viability throughout the 3-day culture period, without the addition of exogenous cytokines. This viability was accompanied by progressive up-regulation of the surface costimulatory (CD40, CD80, CD86) and activation (CMRF-44, CMRF-56, CD83) molecules. The survival and apparent production of DCs in PBMC culture (without exogenous cytokines) and that of sorted DCs (with cytokines) were evaluated and compared by using TruCOUNT analysis. Absolute DC counts increased (for CD123hi and CD11c+ subsets) after overnight culture of PBMCs. Single-cell lineage depletion experiments demonstrated the rapid and spontaneous emergence of “new” in vitro generated DCs from CD14+/CD16+ PBMC radioresistant precursors, additional to the preexisting ex vivo DC population. Unlike monocyte-derived DCs, blood DCs increased dextran uptake with culture and activation. Finally, DCs obtained after culture of PBMCs for 3 days were as effective as freshly isolated DCs in stimulating an allogeneic mixed leukocyte reaction.
IgG plasma cells display a unique spectrum of leukocyte adhesion and homing molecules
Authors: Underhill Gregory H. , Minges-Wols Heather A. , Fornek Jamie L. , Witte Pamela L. , Kansas Geoffrey S. 
Published: October 2002

AbstractLong-lived antibody-secreting plasma cells are formed in the secondary lymphoid organs and subsequently home to the bone marrow, although the mechanisms that control this migration remain primarily unknown. In this study, we show that IgG plasma cells constitute a significant fraction of cervical lymph node cells from older mice deficient in both E- and P-selectin (E/P−/−), and that these cells can be prospectively isolated by phenotype. These IgG plasma cells were polyclonal, cytoplasmic Ig+, spontaneously secreted antibody, were in the G0/G1 phase of the cell cycle, and failed to express multiple B-cell surface markers. The plasma cells exhibited up-regulated cell surface expression of multiple adhesion molecules, including α4 and leukocyte function-associated antigen 1 (LFA-1) integrins, CD44, and P-selectin glycoprotein ligand 1 (PSGL-1). IgG plasma cells bound to vascular cell adhesion molecule 1 (VCAM-1) significantly better than IgM+B cells, indicating that the α4 integrins were constitutively active. A subset of IgG plasma cells also bound hyaluronic acid, the ligand for CD44. In addition, the IgG plasma cells interacted strongly with E-selectin, but poorly with P-selectin, despite elevated levels of PSGL-1 protein. The preferential interaction of plasma cells with E-selectin, but not P-selectin, correlated with elevated α1,3-fucosyltransferase-VII messenger RNA levels, but selective down-regulation of core 2 β1-6-N-glucosaminyltransferase levels, compared to B cells. These results demonstrate a unique adhesion profile for murine IgG plasma cells. Furthermore, the E/P−/− mice represent a novel system to isolate and purify significant numbers of primary IgG plasma cells.
Human Immune Associated Nucleotide 1: a member of a new guanosine triphosphatase family expressed in resting T and B cells
Authors: Cambot Marie , Aresta Sandra , Kahn-Perlès Brigitte , de Gunzburg Jean , Roméo Paul-Henri 
Published: October 2002

AbstractTAL-1 is a basic helix-loop-helix oncoprotein that is expressed in up to 30% of T-cell acute lymphoblastic leukemias but not in the T lineage. We have cloned a complementary DNA, called Human Immune Associated Nucleotide 1 (hIAN1), whose messenger RNA (mRNA) level expression is inversely correlated to the TAL-1 mRNA level in human leukemic T-cell lines. The hIAN1 encodes a 38-kd protein that belongs to a novel family of proteins conserved from plants to humans and characterized by motifs related to, but highly divergent from, the consensus motifs found in guanosine triphosphate (GTP)–binding proteins. Despite these divergent amino acids at positions involved in GTP/guanosine diphosphate (GDP) binding and guanosine triphosphatase (GTPase) activities, we found that hIAN1 specifically binds GDP (Kd = 0.47 μM) and GTP (Kd = 6 μM) and exhibits intrinsic GTPase activity. Among mature hematopoietic cells, hIAN1 is specifically expressed in resting T and B lymphocytes, and its expression level tremendously decreased at the protein but not the mRNA level during B- or T-lymphocyte activation, suggesting a specific role for this new type of GTPase during the immune response.
Population depletion activates autonomous CD154-dependent survival in biopsylike Burkitt lymphoma cells
Authors: Challa Anita , Eliopoulos Aristides G. , Holder Michelle J. , Burguete Alondra Schweizer , Pound John D. , Chamba Anita , Grafton Gillian , Armitage Richard J. , Gregory Christopher D. , Martinez-Valdez Hector , Young Lawrence , Gordon John 
Published: October 2002

AbstractPopulation size is governed through cells reacting to a variety of intrinsic and extrinsic cues. Tumors, while liberated from many of the homeostatic constraints placed on physiologic counterparts, can nonetheless remain subject to both social and environmental control. Burkitt lymphoma cells faithful to the biopsy phenotype were used to model the reliance of the colony, if any, on an inbuilt population sensor. Below a normally suicidal threshold number of cells, low picomolar quantities of exogenous CD40 ligand (CD40L/CD154) were found to sustain the clone without the discernible shift in phenotype that accompanies high CD40L encounter. Although CD154 was undetectable in populous cultures, message was induced as numbers became limiting. Correspondingly, attempts to neutralize endogenous CD40L activity failed to perturb cells at optimal densities but resulted in their marked decline as the critical threshold was approached. These data reveal an auto-inducible survival mechanism seemingly regulated through the monitoring of population size, a process somewhat akin to that of “quorum sensing” among gram-negative bacteria in which diffusible molecules provide a means of communication to coordinate gene expression with population density. This process could be activated as cells discern depletions in their community or when deprived of signals otherwise furnished within an appropriate environmental niche.
A small outbreak of Legionnaires' disease in a cargo ship under repair
Authors: Caylà J.A. , Maldonado R. , González J. , Pellicer T. , Ferrer D. , Pelaz C. , Gracia J. , Baladrón B. , Plaséncia A. 
Published: October 2002

It was reported that two mechanics working on a cargo ship under repair in the port of Barcelona had died after having fever.An investigation was made into the possibility of any additional cases and the presence ofLegionella pneumophilain the ship they were repairing and in their hotel. The contaminated water system was treated with sodium hypochlorite.Both patients died after having been repeatedly diagnosed as having influenza. The two cases occurred among those who had been working with the pump of the ship's water system, while no cases were observed among the other workers (p=0.02). Various serogroups ofL. pneumophilawere isolated from the ship's water pump and distribution system. However, organism of serogroup 1, subgroup Pontiac (Knoxville) were identified with identical deoxyribonucleic acid (DNA) patterns in the lung tissue of one patient and in the cooling water circuit valve of the ship's water pump. The first postintervention control water samples showed no further growth of legionella, but serogrups 4 and 8 were identified 8 months later.This legionellosis outbreak, although small, was highly lethal, probably due to the high levels of bacteria to which the patients were exposed and also because of the failure of correct diagnosis. International recommendations on prevention and control of legionellosis, which include ships under repair, are required.
Increased nitrotyrosine in exhaled breath condensate in cystic fibrosis
Authors: Balint B. , Kharitonov S.A. , Hanazawa T. , Donnelly L.E. , Shah P.L. , Hodson M.E. , Barnes P.J. 
Published: October 2002

Exhaled nitric oxide (ENO), a marker of inflammation in airway diseases is decreased in cystic fibrosis (CF) patients, perhaps because nitric oxide (NO) is metabolized to oxidative end-products. A stable product, 3-nitrotyrosine, may indicate local formation of reactive nitrogen species.Whether NO metabolites in exhaled breath condensate may be increased in CF patients was investigated. The fractional concentration of ENO (Feno), nitrotyrosine and oxides of nitrogen in exhaled breath condensate from 36 stable CF patients were compared to 14 normal subjects using an enzyme immunoassay and fluorescence assay.Nitrotyrosine levels in breath condensate were increased significantly in stable CF patients, compared with normal subjects (25.3±1.5versus6.3±0.8 ng·mL−1, p<0.0001). There was an inverse correlation between the levels of nitrotyrosine and the severity of lung disease.Fenolevels were significantly lower in CF patients than in normal subjects (4.4±0.3versus5.6±0.4 (parts per billion), p<0.05). No correlation was found between nitrotyrosine andFenolevels in CF. There was no significant difference in the levels of nitrite and nitrate between CF patients and normals.The elevation in nitrotyrosine may reflect increased formation of reactive nitrogen species such as peroxynitrite or direct nitration by granulocyte peroxidases, indicating increased oxidative stress in airways of cystic fibrosis patients.
Influenza: vaccination and treatment
Authors: Stephenson I. , Nicholson K.G. 
Published: October 2002

Few conditions exert such an enormous toll of absenteeism, suffering, medical consultations, hospitalization, death and economic loss as influenza. Patients at high risk of complications and mortality include the elderly and those with pre-existing cardiopulmonary disease.The outbreak in 1997 in Hong Kong, of avian H5N1 influenza in man, which resulted in six deaths among 18 hospitalized cases, and the recent isolation of H9N2 viruses from two children in Hong Kong, are reminders that preparation must be made for the next pandemic. Since the 1970s, efforts to control influenza have mostly focussed on the split product and surface antigen vaccines. These vaccines are of proven efficacy in healthy adults and are effective in elderly people with and without medical conditions putting them at high risk of complications and death following influenza infection.However, vaccine coverage is patchy and often low, and outbreaks of influenza are not uncommon in well-immunized residents of nursing homes. New vaccines and methods of vaccine delivery are being developed in attempts to overcome the limitations of existing vaccines.The antiviral drugs amantadine and rimantadine were developed in the 1960s, but have not been used widely due to their spectrum of activity, rapid emergence of resistance, and adverse effects associated with amantadine. The site of enzyme activity of the influenza neuraminidase is highly conserved between types, subtypes and strains of influenza and has emerged as the target of an exciting new class of antiviral agents that are effective both prophylactically and as therapy.
Pharmacological treatment of the biochemical defect in cystic fibrosis airways
Authors: Rodgers H.C. , Knox A.J. 
Published: October 2002

The understanding of the biochemical defect in cystic fibrosis (CF) has advanced considerably since discovery of the CF gene in 1989 and characterization of its product. Studies showing that the abnormality in chloride flux could be corrected by transfection of wild-type cystic fibrosis transmembrane conductance regulator (CFTR) complimentary deoxyribonucleic acid (cDNA) have led to gene therapy trials on both sides of the Atlantic. However, gene therapy as a treatment for CF has yet to be realized.Pharmacological manipulation of the biochemical defect may provide an alternative or complementary approach to treatment. This review will discuss pharmacological agents in development which could correct the abnormal ion movement.The mechanisms of action of these pharmacological agents can be divided broadly into drugs which affect the most common CF mutation, ΔF508, which increase trafficking of the mutant CF protein to the apical membrane; drugs which increase chloride secretion; and drugs which reduce sodium reabsorption across the apical membrane.Treatment options for cystic fibrosis have developed rapidly since discovery of the cystic fibrosis gene over a decade ago. The targeting of specific therapies for particular cystic fibrosis genotypes and the use of combination treatments of chloride channel openers with sodium channel blockers are likely to be key advances in the next decade.
Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening
Authors: Postma D.S. , Sevette C. , Martinat Y. , Schlösser N. , Aumann J. , Kafé H. 
Published: October 2002

The study addressed the question whether the novel inhaled prodrug corticosteroid ciclesonide is equally effective when inhaled in the morning compared to the evening.For this purpose a double-blind, randomized, parallel group study was initiated in which 209 asthmatic patients (forced expiratory volume in one second=50–90% predicted) inhaled either 200 µg ciclesonide in the morning or in the evening, for 8 weeks. Efficacy was assessed by means of spirometry as well as daily recordings of morning and evening peak expiratory flow (PEF), symptoms and use of rescue medication. The 24-h urinary cortisol excretion was measured to evaluate any effect on hypothalamic-pituitary-adrenol axis.Ciclesonide significantly improved asthma control. Morning and evening administration was shown to be equally effective for the different spirometry variables, evening PEF, symptoms, use of rescue medication and number of asthma exacerbations. Regarding morning PEF, the improvements after evening dosing were more prominent and equivalence of morning and evening administration could not be demonstrated. No relevant influence on cortisol excretion was found.Overall, the study indicates that ciclesonide can be given either in the morning or in the evening to meet the patients' preference and individual medical needs, although evening administration may lead to a more pronounced improvement in morning peak expiratory flow.