bluuebunny/crossref_metadata_2025_split huggingface dataset:
Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency
Authors: Rubocki Ronald J. , Parsa Jennifer R. , Hershfield Michael S. , Sanger Warren G. , Pirruccello Samuel J. , Santisteban Ines , Gordon Bruce G. , Strandjord Sarah E. , Warkentin Phyllis I. , Coccia Peter F. 
Published: July 2002

Abstract
Bone marrow transplantation (BMT) for severe combined immunodeficiency (SCID) with human leukocyte antigen (HLA)-identical sibling donors but no pretransplantation cytoreduction results in T-lymphocyte engraftment and correction of immune dysfunction but not in full hematopoietic engraftment. A case of a 17-month-old girl with adenosine deaminase (ADA) deficiency SCID in whom full hematopoietic engraftment developed after BMT from her HLA-identical sister is reported. No myeloablative or immunosuppressive therapy or graft-versus-host disease (GVHD) prophylaxis was given. Mild acute and chronic GVHD developed, her B- and T-cell functions became reconstituted, and she is well almost 11 years after BMT. After BMT, repeated studies demonstrated: (1) Loss of a recipient-specific chromosomal marker in peripheral blood leukocytes (PBLs) and bone marrow, (2) conversion of recipient red blood cell antigens to donor type, (3) conversion of recipient T-cell, B-cell, and granulocyte lineages to donor origin by DNA analysis, and (4) increased ADA activity and metabolic correction in red blood cells and PBLs.
Interleukin 9 promotes influx and local maturation of eosinophils
Authors: Louahed Jamila , Zhou Yuhong , Maloy W. Lee , Rani Pyapalli U. , Weiss Christine , Tomer Yaniv , Vink Anne , Renauld Jean-Christophe , Van Snick Jacques , Nicolaides Nicholas C. , Levitt Roy C. , Haczku Angela 
Published: July 2002

AbstractThe interleukin 9 (IL-9) pathway has recently been associated with the asthmatic phenotype including an eosinophilic tissue inflammation. The mechanism by which IL-9 affects eosinophils (eos) is not known. To investigate whether this cytokine has a direct activity on the development of eos and eosinophilic inflammation, a model of thioglycolate-induced peritoneal inflammation was used in IL-9 transgenic (TG5) and background strain (FVB) mice. In this model, a transient eosinophilic infiltration in the peritoneal cavity was observed in FVB mice 12 to 24 hours after thioglycolate injection that coincided with peak IL-5 and IL-9 release. In contrast, TG5 mice developed a massive eosinophilia that persisted at high levels (81% of total cells) even 72 hours after thioglycolate injection. Release of eosinophilic major basic protein (MBP), IL-4, and IL-5 to the peritoneal cavity of these mice was significantly increased when compared with the control FVB strain. To study the mechanism by which IL-9 exerts its effect on eos, bone marrow or peritoneal cells were cultured in the presence of IL-5, IL-9, or their combination in vitro. IL-5 alone was able to generate significant numbers of eos in TG5 but not FVB mice, whereas a combination of IL-5 and IL-9 induced marked eosinophilia in both strains indicating a synergism between these 2 cytokines. These data suggest that IL-9 may promote and sustain eosinophilic inflammation via IL-5–driven eos maturation of precursors.
New insights into the thrombopoietic status of patients on dialysis through the evaluation of megakaryocytopoiesis in bone marrow and of endogenous thrombopoietin levels
Authors: Ando Minoru , Iwamoto Yuhsuke , Suda Akio , Tsuchiya Ken , Nihei Hiroshi 
Published: July 2002

AbstractThe thrombopoietic status of patients with uremia remains unclear. This issue was addressed with particular reference to marrow megakaryocytopoiesis and endogenous thrombopoietin (TPO) levels. A study was conducted in 114 patients on hemodialysis, 43 patients on continuous ambulatory peritoneal dialysis, and 48 age-matched controls. Reticulated platelets, a marker of marrow megakaryocytopoiesis, were measured by flow cytometry. Serum TPO levels, platelet-associated IgG (PAIgG) levels, and hepatitis C virus (HCV) antibody titers were also measured by enzyme-linked immunosorbent assay. Circulating and reticulated platelet counts were significantly lower in the patients on dialysis than in the controls. Thrombocytopenia (less than 150 × 109/L) was most frequent in the HCV-positive hemodialysis patients, who had a higher incidences and higher PAIgG titers. The following results were obtained in the HCV-negative dialysis patients: (1) platelet counts chronologically decreased with years on hemodialysis; (2) platelet counts were associated with the reticulated platelet counts; (3) serum TPO levels were significantly elevated in the dialysis patients, responding to the decrease of reticulated platelets; (4) hematocrits had a positive correlation with serum TPO levels, and serum TPO levels were significantly higher in the patients on hemodialysis who did not require recombinant human erythropoietin therapy than in the other patients. In conclusion, thrombocytopenia is a frequent finding in patients on dialysis. The failure of megakaryocyte production could be the principal cause of the platelet reduction, and the peripheral destruction and sequestration of platelets may be concomitantly involved. Elevation of serum TPO may in part serve as an aid to erythropoiesis in dialysis patients.
Targeted disruption of the murine Fanconi anemia gene,Fancg/Xrcc9
Authors: Yang Yi , Kuang Yanan , De Oca Rocio Montes , Hays Tobias , Moreau Lisa , Lu Naifang , Seed Brian , D'Andrea Alan D. 
Published: July 2002

AbstractFanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder characterized by cellular sensitivity to mitomycin C and ionizing radiation. Six FA genes (corresponding to subtypes A, C, D2, E, F, and G) have been cloned, and the encoded FA proteins interact in a common cellular pathway. To further understand the in vivo role of one of these human genes (FANCG), we generated a targeted disruption of murine Fancg and bred mice homozygous for the targeted allele. Similar to the phenotype of the previously described Fancc−/− andFanca−/− mice, theFancg−/− mice had normal viability and no gross developmental abnormalities. Primary splenic lymphocytes, bone marrow progenitor cells, and murine embryo fibroblasts from theFancg−/− mice demonstrated spontaneous chromosome breakage and increased sensitivity to mitomycin C and, to a lesser extent, ionizing radiation. Fancg−/−lymphocytes had a defect in the FA pathway, based on their failure to activate the monoubiquitination of the downstream Fancd2protein in response to IR. Finally,Fancg−/− mice had decreased fertility and abnormal gonadal histology. In conclusion, disruption of theFancg gene confirms the role of Fancg in the FA pathway. The Fancg−/− mouse may be useful as an animal model for future gene therapy and cancer susceptibility studies.
The zebrafish klf gene family
Authors: Oates Andrew C. , Pratt Stephen J. , Vail Brenda , Yan Yi-lin , Ho Robert K. , Johnson Stephen L. , Postlethwait John H. , Zon Leonard I. 
Published: July 2002

AbstractThe Krüppel-like factor(KLF) family of genes encodes transcriptional regulatory proteins that play roles in differentiation of a diverse set of cells in mammals. For instance, the founding memberKLF1 (also known as EKLF) is required for normal globin production in mammals. Five new KLF genes have been isolated from the zebrafish, Danio rerio, and the structure of their products, their genetic map positions, and their expression during development of the zebrafish have been characterized. Three genes closely related to mammalian KLF2 andKLF4 were found, as was an ortholog of mammalianKLF12. A fifth gene, apparently missing from the genome of mammals and closely related to KLF1 and KLF2,was also identified. Analysis demonstrated the existence of novel conserved domains in the N-termini of these proteins. Developmental expression patterns suggest potential roles for these zebrafish genes in diverse processes, including hematopoiesis, blood vessel function, and fin and epidermal development. The studies imply a high degree of functional conservation of the zebrafish genes with their mammalian homologs. These findings further the understanding of theKLF genes in vertebrate development and indicate an ancient role in hematopoiesis for the Krüppel-like factorgene family.
Immunotherapy using heat-shock protein preparations of leukemia cells after syngeneic bone marrow transplantation in mice
Authors: Sato Kazuya , Torimoto Yoshihiro , Tamura Yasuaki , Shindo Motohiro , Shinzaki Hitoshi , Hirai Katsuyuki , Kohgo Yutaka 
Published: July 2002

AbstractHeat-shock proteins (HSPs) act as molecular chaperones binding endogenous antigenic peptides and transporting them to major histocompatibility complexes. HSPs chaperone a broad repertoire of endogenous peptides including tumor antigens. For the immunotherapy of tumors, a strategy using HSPs may be more advantageous than other procedures because the identification of each tumor-specific antigen is not necessary. In this study, the efficacy of immunotherapy against minimal residual leukemia cells using HSP preparations was evaluated. HSP70 and GP96 were purified from syngeneic leukemia cell line A20 and immunized into BALB/c mice during the reconstitution period of the immune system after syngeneic bone marrow transplantation. In this procedure, all mice not immunized were dead within 60 days of A20 inoculation, whereas the survival times of HSP-immunized mice were significantly prolonged. In addition, the depletion of either CD4+ or CD8+ T lymphocyte significantly abrogated this efficacy, indicating that both CD4+ and CD8+ T lymphocytes were required for tumor cell rejection. Moreover, the vaccination of HSPs elicited a specific response of potent CD8+ T lymphocytes cytotoxic against A20 in vitro. These observations suggest that immunization of the complex of HSPs and peptides derived from leukemia cells leads to immune responses. These immune responses are sufficient to reject minimal amounts of leukemia cells for relatively immunocompromised mice after syngeneic bone marrow transplantation.
Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry
Authors: McKenna Robert W. , Washington LaBaron T. , Aquino Deborah B. , Picker Louis J. , Kroft Steven H. 
Published: July 2002

AbstractBone marrow hematogones (B-lymphocyte precursors) may cause problems in diagnosis because of their morphologic and immunophenotypic similarities to neoplastic lymphoblasts. The purposes of this prospective, multiparametric flow cytometry study were to quantify hematogones across age groups and a spectrum of clinical conditions, to identify factors that affect the relative quantity of hematogones, and to compare their immunophenotype with that of neoplastic lymphoblasts. A total of 662 consecutive marrow specimens were analyzed for hematogones using one of two 4-color antibody combinations; hematogones were identified in 528 (79.8%). There was a significant decline in hematogones with increasing age (P &lt; .001), but a broad range was found at all ages and many adults had a relatively high number. Specimens processed by density gradient had a higher mean percent hematogones than those processed by erythrocyte lysis (P &lt; .001). There was a direct decline in hematogones with increasing marrow involvement with neoplastic cells. A total of 8% of the 662 specimens contained 5% or more hematogones: 24.6% of specimens from patients aged less than 16 years and 6.3% from those 16 and older (P &lt; .000 01). Increased hematogones were observed most often in patients with lymphoma, marrow regenerative states, immune cytopenias, and acquired immunodeficiency syndrome. Hematogones always exhibited a typical complex spectrum of antigen expression that defines the normal antigenic evolution of B-cell precursors and lacked aberrant expression. In contrast, lymphoblasts in 49 cases of precursor B-ALL showed maturation arrest and exhibited 1 to 11 immunophenotypic aberrancies. Four-color flow cytometry with optimal combinations of antibodies consistently distinguishes between hematogones and neoplastic lymphoblasts.
Slow, programmed maturation of the immunoglobulin HCDR3 repertoire during the third trimester of fetal life
Authors: Schroeder Harry W. , Zhang Liming , Philips Joseph B. 
Published: July 2002

AbstractThe mean distribution of lengths in the third complementarity-determining region of the heavy chain (HCDR3) serves as a measure of the development of the antibody repertoire during ontogeny. To determine the timing and pattern of HCDR3 length maturation during the third trimester of pregnancy, the mean distribution of HCDR3 lengths among variable-diversity-joining-constant–μ (VDJCμ) transcripts from the cord blood was analyzed from 138 infants of 23 to 40 weeks' gestation, including 3 sets of twins, 2 of which were of dizygotic origin. HCDR3 maturation begins at the start of the third trimester; follows a slow, continuous expansion over a 5-month period; and is unaffected by race or sex. The range and mean distribution of lengths may vary in dizygotic twins, indicating individual rates of development. The mean HCDR3 length distribution in 10 premature infants with documented bacterial sepsis was then followed for 2 to 12 weeks after their first positive blood culture. HCDR3 spectrotype analysis demonstrated oligoclonal B-cell activation and expansion after sepsis, but maturation of the repertoire was not accelerated even by the systemic exposure to external antigen represented by bacteremia. Antibody repertoire development appears to be endogenously controlled and adheres to an individualized developmental progression that probably contributes to the relative immaturity of the neonatal immune response.
Erythropoietin receptor-dependent erythroid colony-forming unit development: capacities of Y343 and phosphotyrosine-null receptor forms
Authors: Miller Chris P. , Heilman Destin W. , Wojchowski Don M. 
Published: July 2002

AbstractRed cell development depends on the binding of erythropoietin (EPO) to receptors expressed by erythroid colony-forming units (CFUe) and the subsequent activation of receptor-bound Janus kinase (Jak2). Jak2 then mediates the phosphorylation of receptor tyrosine sites and the recruitment of 25 or more Src homology 2 domain-encoding proteins and associated factors. Previous studies have shown that an EPO receptor form containing Jak2-binding domains plus a single phosphotyrosine343 (PY343)–STAT5-binding site provides all signals needed for erythroid cell development. However, roles for PY343 and STAT5 remain controversial, and findings regarding PY-null receptor activities and erythropoiesis in STAT5-deficient mice are disparate. To study activities of a PY-null EPO receptor in primary cells while avoiding compensatory mechanisms, a form retaining domains for Jak2 binding and activation, but lacking all cytoplasmic tyrosine sites, was expressed in transgenic mice from aGATA1 gene-derived vector as a human epidermal growth factor receptor- murine EPO receptor chimera (EE-T-Y343F). The bio-signaling capacities of this receptor form were investigated in CFUe from thiamphenicol-treated mice. Interestingly, this PY-null EPO receptor form supported CFUe development (in the absence of detectable STAT5 activation) at efficiencies within 3-fold of those levels mediated by either an EE-T-Y343 form or the endogenous EPO receptor. However, EE-T-Y343F–dependent Ter119+ erythroblast maturation was attenuated. In tests of cosignaling with c-Kit, EE-T-Y343F nonetheless retained full capacity to synergize with c-Kit in promoting erythroid progenitor cell proliferation. Thus, EPO receptor PY-dependent events can assist late erythropoiesis but may be nonessential for EPO receptor–c-Kit synergy.
Measuring vocabulary size in English as an additional language
Authors: Cameron Lynne 
Published: July 2002

The paper reports findings from a study in two stages to trial tests of vocabulary size in English as an additional language (EAL). The first, pilot, stage trialled the Levels test (Nation, 1990) and the Yes/No test (Meara, 1992) with secondary students aged 15 years, with an average of 11 years of education in the target language. The Levels test was found more useful, mainly because the inclusion of non-words in the Yes/No test produced unreliable results. In the second stage, the Levels test was used with students aged 13 and 14 years, 63 students for whom English was an additional language, and 84 monolingual English speakers. The results of the tests show a different profile of scores for EAL than occur in typical EFL contexts. EAL students, who have had on average 10.5 years in English medium education, show gaps in their knowledge of the most frequent words and more serious problems with less frequent words, with important implications for educational achievement. Comparison of mean scores of EAL students and their native speaker peers using t-tests reveal significant differences at 3K and 5K levels. The study shows that the Levels test offers a useful research and pedagogic tool in additional language learning contexts, yielding an overall picture of receptive vocabulary learning across groups. The test also produces information about individual language development that may help teaching. Implications include the need for further research into the effects of learning environments on language development, andvthe need for skilled intervention in additional language development to continue throughout secondary schooling.
Phase II Study of Oxaliplatin and Fluorouracil in Taxane- and Anthracycline-Pretreated Breast Cancer Patients
Authors: Zelek L. , Cottu P. , Tubiana-Hulin M. , Vannetzel J.-M. , Chollet Ph. , Misset J.-L. , Chouaki N. , Marty M. , Gamelin E. , Culine S. , Dieras V. , Mackenzie S. , Spielmann M. 
Published: July 2002

PURPOSE: Phase II study evaluating efficacy and safety of combined oxaliplatin/fluorouracil (5-FU) in taxane-pretreated advanced and metastatic breast cancer (ABC) patients. PATIENTS AND METHODS: Sixty-four taxane- and anthracycline-pretreated (within 6 months of study entry) women were treated with oxaliplatin 130 mg/m2 (2-hour intravenous [IV] infusion), day 1, and 5-FU 1,000 mg/m2/d (continuous IV infusion) days 1 to 4, every 3 weeks. RESULTS: Median patient age was 51 years (range, 34 to 71 years), with a median of two involved organs (range, one to six organs), and metastases in the liver (70%), bone (47%), and lung (34%). Patients had a median of two prior chemotherapy regimens (range, one to six regimens), and 78% had previous hormonal therapy, with clinical taxane and anthracycline resistance in 53% and 34%, respectively. A total of 367 cycles were administered, with a median of six cycles/patient (range, one to 15 cycles). Sixty patients were assessable for response (World Health Organization criteria): 17 partial response, 26 stable disease, and 17 disease progression, giving an overall response rate of 27% (95% confidence interval, 16.3% to 39.1%), and 26% and 36% in taxane- and anthracycline-resistant populations, respectively, all responders having metastatic liver disease. Median time to progression was 4.8 months, and median overall survival was 11.9 months. Four treatment-related serious adverse events occurred, seven patients withdrew because of treatment-related toxicity. Hematotoxicity was prevalent but rarely severe, with grade 3-4 neutropenia, leukopenia, and thrombocytopenia in 34%, 19%, and 16% of patients, respectively, and a single episode of febrile neutropenia. One third of patients developed grade 2-3 peripheral neuropathy (oxaliplatin-specific scale), with grade 3 in only 8%. CONCLUSION: This oxaliplatin/5-FU combination is effective with an excellent safety profile in anthracycline/taxane-pretreated ABC patients, showing encouraging activity in patients with anthracycline/taxane-resistance or visceral disease.
Barriers to Optimal Clinician Guideline Adherence in Management of Markedly Elevated Blood Pressure
Authors: Lu Yuan , Arowojolu Oreoluwa , Qiu Xiaoliang , Liu Yuntian , Curry Leslie A. , Krumholz Harlan M. 
Published: August 2024

IMPORTANCEHypertension poses a substantial public health challenge. Despite clinical practice guidelines for hypertension management, clinician adherence to these guidelines remains suboptimal.OBJECTIVETo develop a taxonomy of suboptimal adherence scenarios for severe hypertension and identify barriers to guideline adherence.DESIGN, SETTING, and PARTICIPANTSThis qualitative content analysis using electronic health records (EHRs) of Yale New Haven Health System included participants who had at least 2 consecutive visits with markedly elevated blood pressure (BP; defined as at least 2 consecutive readings of systolic BP ≥160 mm Hg and diastolic BP ≥100 mm Hg) between January 1, 2013, and December 31, 2021, and no prescription for antihypertensive medication within a 90 days of the second BP measurement. Data analysis was conducted from January to December 2023.MAIN OUTCOMES AND MEASURESThe primary outcome was scenarios and influencing factors contributing to clinician nonadherence to the guidelines for hypertension management. A thematic analysis of EHR data was conducted to generate a pragmatic taxonomy of scenarios of suboptimal clinician guideline adherence in the management of severe hypertension.RESULTSOf the 20 654 patients who met criteria, 200 were randomly selected and thematic saturation was reached after analyzing 100 patients (mean [SD] age at index visit, 66.5 [12.8] years; 50 female [50%]; 8 Black [8%]; 5 Hispanic or Latino [5%]; 85 White [85%]). Three content domains emerged: (1) clinician-related scenarios (defined as noninitiation or nonintensification of treatment due to issues relating to clinician intention, capability, or scope), which included 2 subcategories (did not address and diffusion of responsibility); (2) patient-related scenarios (defined as noninitiation or nonintensification of treatment due to patient behavioral considerations), which included 2 subcategories (patient nonadherence and patient preference); and (3) clinical complexity–related scenarios (defined as noninitiation or nonintensification of treatment due to clinical situational complexities), which included 3 subcategories (diagnostic uncertainty, maintenance of current intervention, and competing medical priorities).CONCLUSIONS AND RELEVANCEIn this qualitative study of EHR data, a taxonomy of suboptimal adherence scenarios for severe hypertension was developed and barriers to guideline adherence were identified. This pragmatic taxonomy lays the foundation for developing targeted interventions to improve clinician adherence to guidelines and patient outcomes.