bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experiences of partners of people in the early stages of multiple sclerosis
Authors: Bogosian A , Moss-Morris R , Yardley L , Dennison L 
Published: January 2009

BackgroundPartners of people with multiple sclerosis are known to experience a heavy physical and psychological burden. However, little research has explored, in detail, the partners’ experience in the first years after diagnosis. The aim of this study was to explore and describe the experiences of partners of people who are in the relatively early stages of multiple sclerosis.MethodsFifteen semi-structured telephone interviews were conducted to assess partners’ concerns and difficulties. Data were audio-taped, transcribed, and analysed using an inductive thematic analysis.ResultsKey themes were being unsure of what the future might hold and feeling helpless and out of control. Furthermore, partners reported that other people could not understand and support them, which led to a feeling of social isolation.ConclusionThe research illustrates the disruptive impact that MS has on partners’ lives and highlights the need for support to focus on partners’ needs even in early stages of the disease.
High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle
Authors: Tipping Alex J. , Pina Cristina , Castor Anders , Hong Dengli , Rodrigues Neil P. , Lazzari Lorenza , May Gillian E. , Jacobsen Sten Eirik W. , Enver Tariq 
Published: January 2009

Abstract
Evidence suggests the transcription factor GATA-2 is a critical regulator of murine hematopoietic stem cells. Here, we explore the relation between GATA-2 and cell proliferation and show that inducing GATA-2 increases quiescence (G0 residency) of murine and human hematopoietic cells. In human cord blood, quiescent fractions (CD34+CD38−HoechstloPyronin Ylo) express more GATA-2 than cycling counterparts. Enforcing GATA-2 expression increased quiescence of cord blood cells, reducing proliferation and performance in long-term culture-initiating cell and colony-forming cell (CFC) assays. Gene expression analysis places GATA-2 upstream of the quiescence regulator MEF, but enforcing MEF expression does not prevent GATA-2–conferred quiescence, suggesting additional regulators are involved. Although known quiescence regulators p21CIP1 and p27KIP1 do not appear to be responsible, enforcing GATA-2 reduced expression of regulators of cell cycle such as CCND3, CDK4, and CDK6. Enforcing GATA-2 inhibited human hematopoiesis in vivo: cells with highest exogenous expression (GATA-2hi) failed to contribute to hematopoiesis in nonobese diabetic–severe combined immunodeficient (NOD-SCID) mice, whereas GATA-2lo cells contributed with delayed kinetics and low efficiency, with reduced expression of Ki-67. Thus, GATA-2 activity inhibits cell cycle in vitro and in vivo, highlighting GATA-2 as a molecular entry point into the transcriptional program regulating quiescence in human hematopoietic stem and progenitor cells.
Increased T-bet+ cytotoxic effectors and type I interferon–mediated processes in chronic graft-versus-host disease of the oral mucosa
Authors: Imanguli Matin M. , Swaim William D. , League Stacy C. , Gress Ronald E. , Pavletic Steven Z. , Hakim Frances T. 
Published: January 2009

AbstractAlthough chronic graft-versus-host disease (cGVHD) is a major long-term complication of allogeneic hematopoietic stem cell transplantation, little is known of its pathogenesis. We have systematically examined oral mucosa among cGVHD patients and determined that the clinical severity of oral cGVHD was correlated with apoptotic epithelial cells, often found adjacent to infiltrating effector-memory T cells expressing markers of cytotoxicity and type I cytokine polarization. Accumulation of T-bet+ T-cell effectors was associated with both increased proliferation and the expression of the type I chemokine receptor CXCR3. Concurrently, in both infiltrating cells and keratinocytes, we observed increased expression of the CXCR3 ligand MIG (CXCL9) and interleukin-15 (IL-15), type I interferon (IFN)–inducible factors that support the migration, type I differentiation, and expansion of alloreactive effectors. In severely affected mucosa, we observed high levels of MxA, a protein specifically induced by type I IFN, and signal transducer and activator of transcription 1 (STAT1) phosphorylation, a critical step in the IFN-signaling pathway, along with increased numbers of plasmacytoid dendritic cells. These data challenge the current paradigm of cGVHD as a type II cytokine–driven disorder and support the model that oral cGVHD results from type I IFN–driven immigration, proliferation, and differentiation of T-bet+ type I T effectors. The clinical trials are registered at http://www.clinicaltrials.gov as NCT00331968.
Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features
Authors: Figueroa Maria E. , Wouters Bas J. , Skrabanek Lucy , Glass Jacob , Li Yushan , Erpelinck-Verschueren Claudia A. J. , Langerak Anton W. , Löwenberg Bob , Fazzari Melissa , Greally John M. , Valk Peter J. M. , Melnick Ari , Delwel Ruud 
Published: January 2009

Abstract
Acute myeloid leukemia is a heterogeneous disease from the molecular and biologic standpoints, and even patients with a specific gene expression profile may present clinical and molecular heterogeneity. We studied the epigenetic profiles of a cohort of patients who shared a common gene expression profile but differed in that only half of them harbored mutations of the CEBPA locus, whereas the rest presented with silencing of this gene and coexpression of certain T-cell markers. DNA methylation studies revealed that these 2 groups of patients could be readily segregated in an unsupervised fashion based on their DNA methylation profiles alone. Furthermore, CEBPA silencing was associated with the presence of an aberrant DNA hypermethylation signature, which was not present in the CEBPA mutant group. This aberrant hypermethylation occurred more frequently at sites within CpG islands. CEBPA-silenced leukemias also displayed marked hypermethylation compared with normal CD34+ hematopoietic cells, whereas CEBPA mutant cases showed only mild changes in DNA methylation compared with these normal progenitors. Biologically, CEBPA-silenced leukemias presented with a decreased response to myeloid growth factors in vitro.
Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain
Authors: Gaufin Thaidra , Gautam Rajeev , Kasheta Melissa , Ribeiro Ruy , Ribka Erin , Barnes Mary , Pattison Melissa , Tatum Coty , MacFarland Jeanne , Montefiori David , Kaur Amitinder , Pandrea Ivona , Apetrei Cristian 
Published: January 2009

AbstractWe investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n = 4) and 5 (n = 3) months. Four control animals received no antibody. Three animals were completely depleted of CD20+ B cells, but 4 were only partially depleted of CD20 cells in the LNs and intestine. The decrease in antibody production was consistent with the efficacy of tissue CD20 depletion. Seroconversion and neutralizing antibody production was significantly delayed in animals showing complete tissue CD20 depletion and remained at low titers in all CD20-depleted RMs. Surprisingly, there was no significant difference in acute or chronic viral loads between CD20-depleted and control animal groups. There was a tendency for lower viral set points in CD20-depleted animals. At 6 weeks after inoculation, cellular immune responses were significantly stronger in CD20-depleted animals than in controls. There was no significant difference in survival between CD20-depleted and control animals. Our data suggest that a deficiency of Ab responses did not markedly affect viral replication or disease progression and that they may be compensated by more robust cellular responses.
Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease
Authors: Sarantopoulos Stefanie , Stevenson Kristen E. , Kim Haesook T. , Cutler Corey S. , Bhuiya Nazmim S. , Schowalter Michael , Ho Vincent T. , Alyea Edwin P. , Koreth John , Blazar Bruce R. , Soiffer Robert J. , Antin Joseph H. , Ritz Jerome 
Published: January 2009

AbstractChronic graft-versus-host disease (cGVHD) causes significant morbidity and mortality in patients otherwise cured of malignancy after hematopoietic stem cell transplantation (HSCT). The presence of alloantibodies and high plasma B cell–activating factor (BAFF) levels in patients with cGVHD suggest that B cells play a role in disease pathogenesis. We performed detailed phenotypic and functional analyses of peripheral B cells in 82 patients after HSCT. Patients with cGVHD had significantly higher BAFF/B-cell ratios compared with patients without cGVHD or healthy donors. In cGVHD, increasing BAFF concentrations correlated with increased numbers of circulating pre–germinal center (GC) B cells and post-GC “plasmablast-like” cells, suggesting in vivo BAFF dependence of these 2 CD27+ B-cell subsets. Circulating CD27+ B cells in cGVHD comprised in vivo activated B cells capable of IgG production without requiring additional antigen stimulation. Serial studies revealed that patients who subsequently developed cGVHD had delayed reconstitution of naive B cells despite persistent BAFF elevation as well as proportional increase in CD27+ B cells in the first year after HSCT. These studies delineate specific abnormalities of B-cell homeostasis in patients with cGVHD and suggest that BAFF targeting agents may be useful in this disease.
Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency
Authors: Neven Bénédicte , Leroy Sandrine , Decaluwe Hélène , Le Deist Francoise , Picard Capucine , Moshous Despina , Mahlaoui Nizar , Debré Marianne , Casanova Jean-Laurent , Dal Cortivo Liliane , Madec Yoann , Hacein-Bey-Abina Salima , de Saint Basile Geneviève , de Villartay Jean-Pierre , Blanche Stéphane , Cavazzana-Calvo Marina , Fischer Alain 
Published: January 2009

Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for severe combined immunodeficiency (SCID). Detailed assessment of the long-term outcome of HSCT, ie, the occurrence of clinical events and the quality and stability of immune reconstitution, is now required. We performed a single-center retrospective analysis of the long-term outcome of HSCT in 90-patient cohort followed for between 2 and 34 years (median, 14 years). Clinical events and immune reconstitution data were collected. Almost half the patients have experienced one or more significant clinical events, including persistent chronic graft-versus-host disease (GVHD), autoimmune and inflammatory manifestations, opportunistic and nonopportunistic infections, chronic human papilloma virus (HPV) infections, and a requirement for nutritional support. With the notable exception of severe HPV infection, these complications tend to become less common 15 years later after HSCT. A multivariate analysis showed that the occurrence of these events correlated with non–genoidentical donors, diagnosis of Artemis SCID, and quality of immune reconstitution. In most cases, HSCT enables long-term survival with infrequent sequelae. However, the occurrence of relatively late-onset complications is a concern that requires specific means of prevention and justifies careful patient follow-up.
Caspase-7 deficiency protects from endotoxin-induced lymphocyte apoptosis and improves survival
Authors: Lamkanfi Mohamed , Moreira Lilian O. , Makena Patrudu , Spierings Diana C. J. , Boyd Kelli , Murray Peter J. , Green Douglas R. , Kanneganti Thirumala-Devi 
Published: January 2009

AbstractExtensive apoptosis of leukocytes during sepsis and endotoxic shock constitutes an important mechanism linked to the excessive mortality associated with these disorders. Caspase inhibitors confer protection from endotoxin-induced lymphocyte apoptosis and improve survival, but it is not clear which caspases mediate lipopolysaccharide (LPS)–induced lymphocyte apoptosis and mortality. We report here that the apoptotic executioner caspase-7 was activated in the splenocytes of LPS-injected mice, suggesting a role for caspase-7 in lymphocyte apoptosis. Indeed, caspase-7–deficient mice were resistant to LPS-induced lymphocyte apoptosis and were markedly protected from LPS-induced lethality independently of the excessive production of serum cytokines. These results reveal for the first time a nonredundant role for caspase-7 in vivo and identify caspase-7 inhibition as a component of the mechanism by which caspase inhibitors protect from endotoxin-induced mortality.
Distinct roles of stress-activated protein kinases in Fanconi anemia type C–deficient hematopoiesis
Authors: Saadatzadeh M. Reza , Bijangi-Vishehsaraei Khadijeh , Kapur Reuben , Haneline Laura S. 
Published: January 2009

AbstractThe underlying molecular mechanisms that promote bone marrow failure in Fanconi anemia are incompletely understood. Evidence suggests that enhanced apoptosis of hematopoietic precursors is a major contributing factor. Previously, enhanced apoptosis of Fanconi anemia type C–deficient (Fancc−/−) progenitors was shown to involve aberrant p38 MAPK activation. Given the importance of c-Jun N-terminal kinase (JNK) in the stress response, we tested whether enhanced apoptosis of Fancc−/− cells also involved altered JNK activation. In Fancc−/− murine embryonic fibroblasts, tumor necrosis factor α (TNF-α) induced elevated JNK activity. In addition, JNK inhibition protected Fancc−/− murine embryonic fibroblasts and c-kit+ bone marrow cells from TNF-α-induced apoptosis. Importantly, hematopoietic progenitor assays demonstrated that JNK inhibition enhanced Fancc−/− colony formation in the presence of TNF-α. Competitive repopulation assays showed that Fancc−/− donor cells cultured with the JNK inhibitor had equivalent levels of donor chimerism compared with Fancc−/− donor cells cultured with vehicle control. In contrast, culturing Fancc−/− cells with a p38 MAPK inhibitor significantly increased repopulating ability, supporting an integral role of p38 MAPK in maintaining Fancc−/− hematopoietic stem cell function. Taken together, these data suggest that p38 MAPK, but not JNK, has a critical role in maintaining the engraftment of Fancc−/−-reconstituting cells under conditions of stress.
Patterns of exon-intron architecture variation of genes in eukaryotic genomes
Authors: Zhu Liucun , Zhang Ying , Zhang Wen , Yang Sihai , Chen Jian-Qun , Tian Dacheng 
Published: January 2009

AbstractBackgroundThe origin and importance of exon-intron architecture comprises one of the remaining mysteries of gene evolution. Several studies have investigated the variations of intron length, GC content, ordinal position in a gene and divergence. However, there is little study about the structural variation of exons and introns.ResultsWe investigated the length, GC content, ordinal position and divergence in both exons and introns of 13 eukaryotic genomes, representing plant and animal. Our analyses revealed that three basic patterns of exon-intron variation were present in nearly all analyzed genomes (P< 0.001 in most cases): an ordinal reduction of length and divergence in both exon and intron, a co-variation between exon and its flanking introns in their length, GC content and divergence, and a decrease of average exon (or intron) length, GC content and divergence as the total exon numbers of a gene increased. In addition, we observed that the shorter introns had either low or high GC content, and the GC content of long introns was intermediate.ConclusionAlthough the factors contributing to these patterns have not been identified, our results provide three important clues: common factor(s) exist and may shape both exons and introns; the ordinal reduction patterns may reflect a time-orderly evolution; and the larger first and last exons may be splicing-required. These clues provide a framework for elucidating mechanisms involved in the organization of eukaryotic genomes and particularly in building exon-intron structures.
Characteristics of acute congestive heart failure with normal ejection fraction and less elevated B-type natriuretic peptide
Authors: Shimamoto Ken , Koike Natsuha , Mizuochi Kiyoko , Honma Miho , Kasai Yufuko , Sakai Akiko , Fujita Etsuko , Kawana Masatoshi 
Published: January 2009

Abstract

Background
Heterogeneity in B-type natriuretic peptide (BNP) levels, especially among individuals with acute heart failure with normal left ventricular ejection fraction (HFNEF), can cause confusion in interpreting results. We investigated the characteristics of cases of acute HFNEF with only modestly elevated BNP.

Methods
One hundred forty-two patients with acute or acute exacerbation of chronic HFNEF were divided into two groups by BNP level: BNP < 100 pg/ml (NB group, n = 45) and BNP ≥ 100 pg/ml (B group, n = 97). We compared clinical findings, echocardiography results, and neurohormonal factors between these two groups.

Results
In the NB group, a history of open-heart surgery (OHS) was more frequent (71% vs. 22%, p < 0.0001) and hypertension was less frequent (p = 0.0005). Left atrial diameter (LAd) was higher (p = 0.0026), while interventricular septal thickness, posterior wall thickness, relative wall thickness, left ventricular mass index were lower (p = 0.0005, p = 0.0225, p = 0.0114, p = 0.0051, respectively) in the NB group. In patients with HFNEF, a history of OHS remained an independent predictor of BNP level (< 100 pg/ml) after adjustment for hypertension, age, LAd, and interventricular septal thickness (odds ratio 3.6, p = 0.0252).

Conclusion
We found associations between acute HFNEF with less elevated BNP and a history of OHS. In a patient suspected of HFNEF, a history of OHS is considered diagnostic evidence of presence of diastolic heart failure when plasma levels of BNP are less elevated.
Alteration of renal respiratory Complex-III during experimental type-1 diabetes
Authors: Munusamy Shankar , Saba Hamida , Mitchell Tanecia , Megyesi Judit K , Brock Robert W , MacMillan-Crow Lee Ann 
Published: January 2009

Abstract

Background
Diabetes has become the single most common cause for end-stage renal disease in the United States. It has been established that mitochondrial damage occurs during diabetes; however, little is known about what initiates mitochondrial injury and oxidant production during the early stages of diabetes. Inactivation of mitochondrial respiratory complexes or alteration of their critical subunits can lead to generation of mitochondrial oxidants, mitochondrial damage, and organ injury. Thus, one goal of this study was to determine the status of mitochondrial respiratory complexes in the rat kidney during the early stages of diabetes (5-weeks post streptozotocin injection).

Methods
Mitochondrial complex activity assays, blue native gel electrophoresis (BN-PAGE), Complex III immunoprecipitation, and an ATP assay were performed to examine the effects of diabetes on the status of respiratory complexes and energy levels in renal mitochondria. Creatinine clearance and urine albumin excretion were measured to assess the status of renal function in our model.

Results
Interestingly, of all four respiratory complexes only cytochrome c reductase (Complex-III) activity was significantly decreased, whereas two Complex III subunits, Core 2 protein and Rieske protein, were up regulated in the diabetic renal mitochondria. The BN-PAGE data suggested that Complex III failed to assemble correctly, which could also explain the compensatory upregulation of specific Complex III subunits. In addition, the renal F0F1-ATPase activity and ATP levels were increased during diabetes.

Conclusion
In summary, these findings show for the first time that early (and selective) inactivation of Complex-III may contribute to the mitochondrial oxidant production which occurs in the early stages of diabetes.
Extramedullary leukemia in children presenting with proptosis
Authors: Murthy Ramesh , Vemuganti Geeta K , Honavar Santosh G , Naik Milind , Reddy Vijayanand 
Published: January 2009

Abstract

Background
We highlight the orbital manifestations of acute myeloid leukemia and the role of peripheral blood smear in the diagnosis of these cases. A total of 12 patients who presented with proptosis and were subsequently diagnosed to have acute myeloid leukemia based on incision biopsy or peripheral blood smear were included in the study.

Results
A retrospective review of all cases of acute myeloid leukemia presenting to the Orbital clinic was performed. The age at presentation, gender, presenting features, duration of symptoms and fundus features were noted. In addition the temporal relationship of the orbital disease to the diagnosis of leukemia, laterality, location of the orbital mass, imaging features and the diagnostic tools used to diagnose leukemia were noted. The median age at presentation was 6 years. The male: female ratio was 0.7:1. None of these patients had been diagnosed earlier as having acute myeloid leukemia. The presenting features included proptosis in all patients, orbital mass in 5 (41.7%), visual symptoms in 2 (16.7%) and subconjunctival hemorrhage in one patient (8.3%). A diagnosis of acute myeloid leukemia was established by incision biopsy in 4 patients, subsequently confirmed by peripheral blood smear testing and bone marrow biopsy in 2 patients which revealed the presence of systemic involvement. Imprint smears of the biopsy identified blasts in 2 of 4 cases. In 8 patients presenting with ocular manifestations, diagnosis was established by peripheral blood smear examination alone which revealed a diagnosis of acute myeloid leukemia.

Conclusion
A peripheral blood smear should be performed in all cases of sudden onset proptosis or an orbital mass in children and young adults along with an orbital biopsy. It can always be complemented with a bone marrow biopsy especially in cases of aleukemic leukemia or when the blood smear is inconclusive.