bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired production of naive T lymphocytes in human T-cell leukemia virus type I–infected individuals: its implications in the immunodeficient state
Authors: Yasunaga Jun-ichirou , Sakai Tatsunori , Nosaka Kisato , Etoh Ken-ichiro , Tamiya Sadahiro , Koga Shin , Mita Shuji , Uchino Makoto , Mitsuya Hiroaki , Matsuoka Masao 
Published: July 2002

Abstract
Opportunistic infections frequently occur in patients with adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I) carriers. However, the underlying mechanisms of such infections remain unknown. To clarify the mechanism of immunodeficiency in those infected with HTLV-I, this study analyzed the T-cell subsets in HTLV-I carriers and patients with HTLV-I–associated myelopathy/tropical spastic paraparesis and ATL using 3-color fluorescence with CD62L and CD45RA coexpression either with CD4+ or CD8+ T cells. The number of naive T lymphocytes was markedly suppressed in patients with ATL, particularly in those with acute form, compared with uninfected control individuals. The number of naive T cells was low in HTLV-I–infected individuals under 50 years old compared with uninfected individuals, whereas the number of memory T lymphocytes was greater in HTLV-I–infected individuals. Although the increase of memory T lymphocytes correlated with HTLV-I provirus loads, no relationship was found between naive T-cell counts and provirus loads. T-cell receptor rearrangement excision circles (TRECs), which are generated by DNA recombination during early T lymphopoiesis, were quantified to evaluate thymic function in HTLV-I–infected individuals. TREC levels were lower in HTLV-I–infected individuals than in uninfected individuals. In HTLV-I carriers less than 70 years old, an increase of Epstein-Barr virus DNA in peripheral blood mononuclear cells was observed in 6 of 16 (38%) examined, whereas it was detectable in only 1 of 11 uninfected controls. These results suggested that the low number of naive T lymphocytes was due to suppressed production of T lymphocytes in the thymus, which might account for immunodeficiency observed in HTLV-I–infected individuals.
A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model
Authors: Moskowitz Craig H. , Nimer Stephen D. , Zelenetz Andrew D. , Trippett Tania , Hedrick Eric E. , Filippa Daniel A. , Louie Diane , Gonzales Maria , Walits Janine , Coady-Lyons Nancy , Qin Jing , Frank Richard , Bertino Joseph R. , Goy Andre , Noy Ariela , O'Brien James P. , Straus David , Portlock Carol S. , Yahalom Joachim 
Published: July 2002

Abstract
Salvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dose-dense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P &lt; .001). These results compare favorably with other series and document the feasibility and efficacy of giving uniform dose-dense and dose-intense cytoreductive chemotherapy and integrating accelerated fractionation radiotherapy into an ASCT treatment program. This prognostic model provides a basis for risk-adapted HDT.
The arginine-552-cysteine (R1315C) mutation within the A1 loop of von Willebrand factor induces an abnormal folding with a loss of function resulting in type 2A–like phenotype of von Willebrand disease: study of 10 patients and mutated recombinant von Willebrand factor
Authors: Ribba Anne-Sophie , Hilbert Lysiane , Lavergne Jean-Maurice , Fressinaud Edith , Boyer-Neumann Catherine , Ternisien Catherine , Juhan-Vague Irène , Goudemand Jenny , Girma Jean-Pierre , Mazurier Claudine , Meyer Dominique 
Published: July 2002

AbstractThe study identified 10 patients from 6 families with prolonged bleeding time, decreased von Willebrand factor (vWF) ristocetin cofactor activity (RCoF) to vWF:Ag (antigen) ratio, and reduced ristocetin-induced platelet agglutination as well as ristocetin- or botrocetin-induced binding of plasma vWF to platelet glycoprotein Ib (GpIb). In addition, all patients showed a decrease of intermediate-molecular-weight (intermediate-MW) and high-molecular-weight (HMW) multimers of vWF. In the heterozygous state, a cysteine-to-threonine (C → T) transversion was detected at nucleotide 4193 of the VWF gene of all patients and lead to the arginine (R)522C substitution in the A1 loop of vWF mature subunit (R1315C in the preprovWF). By in vitro mutagenesis of full-length complementary DNA (cDNA) of vWF and transient expression in COS-7 cells, the mutated C552 recombinant vWF (C552rvWF) was found to exhibit decreased expression, abnormal folding, and lack of intermediate-MW and HMW multimers. In addition, direct binding of botrocetin to C552rvWF, as well as ristocetin- and botrocetin-induced binding of C552rvWF to GpIb, was markedly decreased. Although being localized in an area of the A1 loop of vWF where most of the type 2B mutations that induce a gain-of-function have been identified, the R552C mutation induces a 2A-like phenotype with a decrease of intermediate-MW and HMW multimers as well as a loss-of-function of vWF in the presence of either ristocetin or botrocetin.
Regulation of nuclear factor of activated T cells by phosphotyrosyl-specific phosphatase activity: a positive effect on HIV-1 long terminal repeat–driven transcription and a possible implication of SHP-1
Authors: Fortin Jean-François , Barbeau Benoit , Robichaud Gilles A. , Paré Marie-Ève , Lemieux Anne-Marie , Tremblay Michel J. 
Published: July 2002

AbstractAlthough protein tyrosine phosphatase (PTP) inhibitors used in combination with other stimuli can induce interleukin 2 (IL-2) production in T cells, a direct implication of nuclear factor of activated T cells (NFAT) has not yet been demonstrated. This study reports that exposure of leukemic T cells and human peripheral blood mononuclear cells to bis-peroxovanadium (bpV) PTP inhibitors markedly induce activation and nuclear translocation of NFAT. NFAT activation by bpV was inhibited by the immunosuppressive drugs FK506 and cyclosporin A, as well as by a specific peptide inhibitor of NFAT activation. Mobility shift assays showed specific induction of the NFAT1 member by bpV molecules. The bpV-mediated NFAT activation was observed to be important for the up-regulation of the human immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR) and the IL-2 promoter; NFAT1 was demonstrated to be particularly important in bpV-dependent positive action on HIV-1 LTR transcription. The active participation of p56lck, ZAP-70, p21ras, and calcium in the bpV-mediated signaling cascade leading to NFAT activation was confirmed, using deficient cell lines and dominant-negative mutants. Finally, overexpression of wild-type SHP-1 resulted in a greatly diminished activation of NFAT by bpV, suggesting an involvement of SHP-1 in the regulation of NFAT activation. These data were confirmed by constitutive NFAT translocation observed in Jurkat cells stably expressing a dominant-negative version of SHP-1. The study proposes that PTP activity attenuates constitutive kinase activities that otherwise would lead to constant NFAT activation and that this activation is participating in HIV-1 LTR stimulation by PTP inhibition.
Platelet glycoprotein Ibα Kozak polymorphism is associated with an increased risk of ischemic stroke
Authors: Baker Ross I. , Eikelboom John , Lofthouse Elizabeth , Staples Nicole , Afshar-Kharghan Vahid , López José A. , Shen Yang , Berndt Michael C. , Hankey Graeme 
Published: July 2002

AbstractPlatelets are pivotal to the process of arterial thrombosis resulting in ischemic stroke. Occlusive thrombosis is initiated by the interaction of von Willebrand factor (vWf) and platelet glycoprotein (GP) Ibα. Three polymorphisms have been described in GP Ibα (Kozak T/C polymorphism, variable number of tandem repeats [VNTR], and the human platelet antigen 2a [HPA-2a] [Thr] or HPA-2b [Met] at position 145), each of which may enhance the vWf and GP Ibα interaction. This study investigated whether these polymorphisms are candidate genes for first-ever ischemic stroke. A hospital-based case-control study was conducted of 219 cases of first-ever ischemic stroke and 205 community controls randomly selected from the electoral roll and stratified by age, sex, and postal code. The subtypes of stroke were classified, the prevalence of conventional risk factors was recorded, and blood was collected to perform genotyping analysis for Kozak C or T alleles, VNTR, and HPA-2a/b. It was found that the Kozak T/C genotype was over-represented in the stroke group (32.2%) compared with controls (22.8%) (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.54; P &lt; .03), and the association was still present even after adjusting for conventional risk factors. There was a trend in the increased prevalence of HPA-2a/b in stroke patients (15%) compared with controls (9.9%) (adjusted OR, 1.8; 95% CI, 0.94-3.4; P = .07). No associations were seen with the VNTR polymorphism or with any of the polymorphisms with stroke subtype. It was concluded that the Kozak T/C polymorphism, which is associated with an increase in platelet GP Ibα surface expression, is an independent risk factor for first-ever ischemic stroke.
P-selectin mediates the adhesion of sickle erythrocytes to the endothelium
Authors: Matsui Neil M. , Borsig Lubor , Rosen Steven D. , Yaghmai Mitra , Varki Ajit , Embury Stephen H. 
Published: July 2002

AbstractThe adherence of sickle red blood cells (RBCs) to the vascular endothelium may contribute to painful vaso-occlusion in sickle cell disease. Sickle cell adherence involves several receptor-mediated processes and may be potentiated by the up-regulated expression of adhesion molecules on activated endothelial cells. Recent results showed that thrombin rapidly increases the adhesivity of endothelial cells for sickle erythrocytes. The current report presents the first evidence for the novel adhesion of normal and, to a greater extent, sickle RBCs to endothelial P-selectin. Studies of the possible interaction of erythrocytes with P-selectin revealed that either P-selectin blocking monoclonal antibodies or sialyl Lewis tetrasaccharide inhibits the enhanced adherence of normal and sickle cells to thrombin-treated endothelial cells. Both RBC types also adhere to immobilized recombinant P-selectin. Pretreating erythrocytes with sialidase reduces their adherence to activated endothelial cells and to immobilized recombinant P-selectin. Herein the first evidence is presented for the binding of normal or sickle erythrocytes to P-selectin. This novel finding suggests that P-selectin inhibition be considered as a potential approach to therapy for the treatment of painful vaso-occlusion in sickle cell disease.
Blood coagulation at the site of microvascular injury: effects of low-dose aspirin
Authors: Undas Anetta , Brummel Kathleen , Musial Jacek , Mann Kenneth G. , Szczeklik Andrew 
Published: July 2002

AbstractThe sequence of coagulant reactions in vivo following vascular injury is poorly characterized. Using quantitative immunoassays, the time courses were evaluated for activation of prothrombin, factor (F)V, FXIII, fibrinogen (Fbg) cleavage, and FVa inactivation in bleeding-time blood collected at 30-second intervals from 12 healthy subjects both before and after aspirin ingestion. Prothrombin decreased at a maximum rate of 14.2 ± 0.6 nM per second to 10% of initial values at the end of bleeding. Significant amounts of α-thrombin B chain appeared rapidly at 90 seconds of bleeding and increased at a maximum rate of 0.224 ± 0.03 nM per second to a peak value of 38 nM. Kinetics of prethrombin 2 generation was almost identical. Prothrombinase concentration reached a peak value of 22 pM at 150 seconds and then decreased to 9 pM at the end of bleeding. Prothrombin fragment 1.2 (F1.2) was produced explosively (0.673 ± 0.05 nM per second), whereas thrombin-antithrombin III (TAT) complexes were generated at a much slower rate (0.11 ± 0.008 nM per second;P = .002). FVa light chain was detectable 30 seconds later than the heavy chain (150 seconds) and was produced at a slightly slower rate (0.027 ± 0.001 nM per second) when compared with the heavy chain (0.032 ± 0.002 nM per second; P = .041). The 30 000 fragment (residues 307-506) of FVa heavy chain produced by activated protein C appeared as early as at 90 seconds and increased with time. Fbg was removed from the blood shed with a high rate of 0.047 ± 0.02 μM/s and became undetectable at approximately 180 seconds of bleeding. The velocity of FXIII activation correlated with thrombin B-chain formation. A 7-day aspirin administration (75 mg/d) resulted in significant reductions in maximum rates of (1) prothrombin removal (by 29%; P = .008); generation of α-thrombin B-chain (by 27.2%; P = .022), and prethrombin 2 (by 26%; P = .014); formation of F1.2 (by 31.4%;P = .009) and TAT (by 30.3%; P = 0.013); (2) release of FVa heavy chain (by 25%; P = .003) and FVa light chain (by 29.6%; P = .007); (3) Fbg depletion from solution (by 30.5%; P = .002); and (4) FXIII activation (by 28.6%; P = .003). Total amounts of the proteins studied, collected at every interval, also significantly decreased following aspirin ingestion. These results indicate that low-dose aspirin impairs thrombin generation and reactions catalyzed by this enzyme at the site of the injury.
Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells
Authors: Reyes Morayma , Lund Troy , Lenvik Todd , Aguiar Dean , Koodie Lisa , Verfaillie Catherine M. 
Published: July 2002

AbstractIt is here reported that mesenchymal stem cells known to give rise to limb-bud mesoderm can, at the single-cell level, also differentiate into cells of visceral mesoderm and can be expanded extensively by means of clinically applicable methods. These cells were named mesodermal progenitor cells (MPCs). MPCs were selected by depleting bone marrow mononuclear cells from more than 30 healthy human donors of CD45+/glycophorin-A (GlyA)+ cells. Cells were cultured on fibronectin with epidermal growth factor and platelet-derived growth factor BB and 2% or less fetal calf serum. It was found that 1/5 × 103CD45−GlyA− cells, or 1/106 bone marrow mononuclear cells, gave rise to clusters of small adherent cells. Cell-doubling time was 48 to 72 hours, and cells have been expanded in culture for more than 60 cell doublings. MPCs are CD34−, CD44low, CD45−, CD117 (cKit)−, class I–HLA−, and HLA-DR−. MPCs differentiated into cells of limb-bud mesoderm (osteoblasts, chondrocytes, adipocytes, stroma cells, and skeletal myoblasts) as well as visceral mesoderm (endothelial cells). Retroviral marking was used to definitively prove that single MPCs can differentiate into cells of limb bud and visceral mesoderm. Thus, MPCs that proliferate without obvious senescence under clinically applicable conditions and differentiate at the single-cell level not only into mesenchymal cells but also cells of visceral mesoderm may be an ideal source of stem cells for treatment of genetic or degenerative disorders affecting cells of mesodermal origin.
Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study
Authors: Joshi Deval D. , Dang Anju , Yadav Prem , Qian Jing , Bandari Persis S. , Chen Kunhua , Donnelly Robert , Castro Tammy , Gascon Pedro , Haider Ali , Rameshwar Pranela 
Published: July 2002

AbstractHematopoietic regulation is a complex but dynamic process regulated by intercellular and intracellular interactions within the bone marrow (BM) microenvironment. Through neurokinin-1 (NK-1) and NK-2 receptors, peptides (eg, substance P [SP]) encoded by the preprotachykinin-I gene mediate distinct hematopoietic effects. Cytokines, associated with hematopoietic stimulation, and SP regulate the expression of each other in BM mesenchymal and immune cells. Neutral endopeptidase (NEP) uses SP as a substrate to produce SP(1-4), which inhibits the proliferation of matured myeloid progenitor. This study determines whether the degradation of SP to SP(1-4) by endogenous NEP in BM stroma could be a feedback on hematopoietic stimulation by stem cell factor (SCF). SP(1-4) induced the production of transforming growth factor (TGF)–β and tumor necrosis factor–α in BM stroma. TGF–β production accounted for part of the inhibitory effects by SP(1-4) on the proliferation of early (granulocyte-macrophage colony-forming units) and late (long-term culture-initiating cells) hematopoietic progenitors. Enzyme-linked immunosorbent assays and/or protein-chip arrays indicated a timeline change of SP to SP(1-4) in BM stroma stimulated with SCF, which correlated with increase in NEP messenger RNA. Since SP and its fragment, SP(1-4), interact with the same receptor to mediate opposing hematopoietic effects, 2 interactive studies were done to understand the dual responses of NK-1: (1) a 3-dimensional molecular model of NK-1 and SP and (2) screening of a random dodecapeptide library for SP(1-4) interacting sites. The effects of SP(1-4) on hematopoietic progenitors and the timeline change of SP to SP(1-4), together with the 3-dimensional model, provide a partial explanation for the feedback on the stimulatory effects of SCF and SP on hematopoiesis.
Differential gene expression profiling of adult murine hematopoietic stem cells
Authors: Park In-Kyung , He Yaqin , Lin Fangming , Laerum Ole D. , Tian Qiang , Bumgarner Roger , Klug Christopher A. , Li Kaijun , Kuhr Christian , Doyle Michelle J. , Xie Tao , Schummer Michèl , Sun Yu , Goldsmith Adam , Clarke Michael F. , Weissman Irving L. , Hood Leroy , Li Linheng 
Published: July 2002

AbstractHematopoietic stem cells (HSCs) have self-renewal capacity and multilineage developmental potentials. The molecular mechanisms that control the self-renewal of HSCs are still largely unknown. Here, a systematic approach using bioinformatics and array hybridization techniques to analyze gene expression profiles in HSCs is described. To enrich mRNAs predominantly expressed in uncommitted cell lineages, 54 000 cDNA clones generated from a highly enriched population of HSCs and a mixed population of stem and early multipotent progenitor (MPP) cells were arrayed on nylon membranes (macroarray or high-density array), and subtracted with cDNA probes derived from mature lineage cells including spleen, thymus, and bone marrow. Five thousand cDNA clones with very low hybridization signals were selected for sequencing and further analysis using microarrays on glass slides. Two populations of cells, HSCs and MPP cells, were compared for differential gene expression using microarray analysis. HSCs have the ability to self-renew, while MPP cells have lost the capacity for self-renewal. A large number of genes that were differentially expressed by enriched populations of HSCs and MPP cells were identified. These included transcription factors, signaling molecules, and previously unknown genes.
Lifestyle risks for three disease outcomes in spinal cord injury
Authors: Davies Diane S , McColl Mary Ann 
Published: July 2002

Object: The majority of research focusing on lifestyle risks in the spinal cordinjured population to date has mainly been descriptive in nature. Limited research has examined the relationships between lifestyle risks and morbidity. This study was undertaken to quantify the associations between selected lifestyle risks and morbidity associated with three top causes of mortality in adults with spinal cord injury (SCI). Method: Ninety-seven adults who had incurred a spinal cord injury between 1972 and 1992 were interviewed over the telephone to assess morbidity and lifestyle exposure history. Logistic regression modelling was used to assess the association between lifestyle risks and cardiovascular, respiratory and urinary tract disorders. Results: Risk of cardiovascular morbidity was found to be positively associated with age and duration of cigarette use. Risk of respiratory morbidity was found to be positively associated with quadriplegia, number of cigarettes smoked per day, and the interaction between cigarettes smoked per day and excessive alcohol consumption. Risk of urinary tract morbidity was found to be positively associated with a complete lesion, number of cigarettes smoked per day and, surprisingly, physical activity. Risk of urinary tract morbidity was negatively associated with monthly alcohol consumption, a traumatic injury and the interaction between monthly alcohol consumption and a complete lesion. Conclusion: With respect to the three morbidity outcomes in this study, cigarette smoking is the most damaging lifestyle behaviour in the spinal cordinjured population. Attention and resources should be directed towards SCI-speci”c smoking prevention and cessation programmes to prevent the development and exacerbation of chronic diseases in this unique population. Further research is needed to fully understand the associations between lifestyle and chronic diseases in the SCI population.
Characteristics of injured children attending the emergency department: patients potentially in need of rehabilitation
Authors: Sturms Leontien M , van der Sluis Corry K , Groothoff Johan W , Duis Henk Jan ten , Eisma Willem H 
Published: July 2002

Objective: To provide an epidemiological overview of the characteristics of injured children and to compare hospitalized and nonhospitalized injured children to identify predictors of hospitalization and, with that, possible predictors of disablement. Design: Retrospective analysis of data obtained from a computerized trauma registration system and medical records. Setting: Department of Traumatology, University Hospital Groningen, the Netherlands. Subjects: Children (0–19 years) injured in 1996 and 1997 ( n = 5057). Results: The majority of children were injured in home and leisure accidents (53%) and sustained minor injuries. Only 55 (1%) children were severely injured (Injury Severity Score (ISS) 3 16). Overall, 512 (10%) patients required hospitalization, 19 children were referred to a rehabilitation centre, and 24 children died due to their injuries. The majority of these patients were injured in traffic. Compared with the group of nonhospitalized patients, the group of hospitalized patients consisted of more males and traffic victims, were more severely injured, and sustained more head/neck, spine, and thorax and abdomen injuries. Nonhospitalized patients incurred proportionally more upper and lower extremity injuries. The ISS, the body region of most severe injury, and injury cause (traffic accidents) were significant predictors of hospitalization. Conclusions: Young traffic victims, severely injured children in terms of high ISS scores, and children with injuries affecting the head/neck/face or thorax/abdomen carry the highest risk of hospitalization.