bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endocanalicular, High‐Pressure Balloon Catheter, Endoscopic Dacryocystorhinostomy
Authors: Ragab Sameh M. , El‐Koddousy Mona S. , Badr Mohammed 
Published: May 2011

ObjectivesTo conduct a prospective randomized controlled study to investigate the safety and efficacy of endocanalicular, high‐pressure, 5‐mm balloon catheter, endoscopic dacryocystorhinostomy (DCR) in adult patients with acquired complete nasolacrimal obstruction.Study DesignProspective randomized controlled study.SettingGeneral hospital.Subjects and MethodsSixty‐six adult patients with a total of 70 procedures were recruited to undergo endoscopic DCR. They were prospectively, equally randomized into 2 groups: endocanalicular, high‐pressure, 5‐mm balloon catheter, endoscopic DCR (group I) and conventional endoscopic DCR (group II). Regular follow‐up sessions were conducted to document the patient’s subjective improvement, judge ostium patency on irrigation, and record any complications.ResultsBoth groups demonstrated a success rate of 91.4%. There was a shorter mean operative time (25.7 minutes) in group I (P <. 001). The number of adverse events was significantly higher in group II (P <. 05). Group I showed statistically significantly more comfort during surgery under local anesthesia with minimal sedation (P <. 05).ConclusionEndocanalicular balloon catheter endoscopic DCR shares the advantages and success rate of conventional endoscopic DCR. In addition, the former is simpler, requires less manipulation, consumes a shorter operative time, has a better safety profile, and can be conducted under local anesthesia with minimal sedation.
Expression of Chitinases in Hypertrophied Adenoids of Children
Authors: Heo Kyung Wook , Hur Dae Young , Park Seong Kook , Yang Young Il , Kwak Hyun Ho , Kim Tae Yong 
Published: May 2011

Objectives/HypothesisChronic rhinosinusitis (CRS), otitis media with effusion (OME), and allergic rhinitis (AR) are common conditions that have been associated with hypertrophied adenoids in children, and adenoidectomy is clinically recommended. The investigators assayed the expression level and site of acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) in hypertrophied adenoids of children to determine the expression levels of 2 chitinases in relation to CRS, OME, and AR.Study DesignA prospective cohort study.SettingA tertiary care facility.MethodsHypertrophied adenoids from 41 children were harvested during adenoidectomy. Medical records were reviewed and the subjects were grouped according to the presence of CRS, OME, and AR. Messenger RNA (mRNA) and protein expression of AMCase and ChT in adenoid tissues was assessed by reverse transcription polymerase chain reaction and Western blotting. Immunohistochemical staining revealed the sites of AMCase and ChT expression.ResultsmRNA and protein of AMCase and ChT were present in adenoids of all subjects. CRS was a significant variable in AMCase mRNA and protein expression. CRS, OME, and AR were significant variables in ChT mRNA and protein expression. Both AMCase and ChT were expressed in histiocytes and vascular endothelial cells of adenoid tissues.ConclusionsThe findings suggest that chitin‐containing pathogens or dysregulated immune responses to them in the hypertrophied adenoids of children could be factors contributing to CRS, OME, and AR via AMCase or ChT overexpression.
Pregnancy and natalizumab: results of an observational study in 35 accidental pregnancies during natalizumab treatment
Authors: Hellwig Kerstin , Haghikia Aiden , Gold Ralf 
Published: May 2011

Background: Natalizumab, a therapeutic monoclonal antibody approved for the treatment of relapsing–remitting multiple sclerosis (RRMS), is recommended to be withdrawn 3 months prior to a planned pregnancy. Our aim was to analyse the safety and impact of natalizumab exposure on course of disease and pregnancy outcome. Objectives: Prospective follow-up of women with MS who became accidentally pregnant during natalizumab treatment in comparison with pregnancies of women with MS not exposed to disease-modifying treatments (DMT). Method: 35 women with MS who became accidentally pregnant while treated with natalizumab, and 23 women with MS who became pregnant devoid of any DMT as a control group, were chosen. Results: All pregnancies except one were followed in a prospective fashion. Of the women exposed to natalizumab during pregnancy, 29 women gave birth to 28 healthy children; one child was born with hexadactyly. Five pregnancies ended in an early miscarriage and one woman decided to undergo an elective termination of pregnancy. MS activity did not rebound during pregnancy or post partum after natalizumab was withdrawn, and no significant differences were observed when compared with the non-DMT-exposed control group. Conclusion: Our data may support the notion that an elective termination of pregnancy due to natalizumab exposure may not be necessary, but rather requires careful monitoring. Women should still be advised to stop natalizumab in the course of planned pregnancy until more data on long-term outcomes are available.
Cardiovascular pre-participation screening does not distress professional football players
Authors: Solberg EE , Bjørnstad TH , Andersen TE , Ekeberg Ø 
Published: May 2011

Background: It has been debated whether cardiovascular screening of athletes creates negative psychological reactions in those being screened. Neither the athletes’ level of distress towards, nor their opinion about screening has actually been examined. Therefore, the aim of this study was to assess the level of distress among Norwegian elite male football players and their experiences of screening. Methods: After screening, players completed a 10-item scale assessing their experience on a Likert scale. Their level of distress was measured with the intrusion sub-scale of Impact of Event Scale (IES) (7 items) on a six-point scale (grade 0–5). A sum score of ≥19 indicates a clinical stress problem. Twenty-five out of 28 teams, 441 of 591 players (75%, mean age 26 [18–39] years) consented to participate. Results: Sixty-four percent felt more confident when playing football and 88% were satisfied having completed the screening. The majority (77%) felt a need for the screening and 84% would strongly recommend it to others. Sixteen percent were afraid that the screening result might have consequences for their own health, and 13% were afraid of losing their license to play football. Less than 3% experienced distress (IES ≥ 19). Conclusions: The majority of the players were satisfied having completed the screening, felt more confident and would recommend it to other players. Only a marginal proportion of the players were distressed by the screening, but were at least as likely to recommend it.
Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia
Authors: Almalte Zaema , Samarani Suzanne , Iannello Alexandre , Debbeche Olfa , Duval Michel , Infante-Rivard Claire , Amre Devendra K. , Sinnett Daniel , Ahmad Ali 
Published: May 2011

Abstract
Acute lymphoblastic leukemia of pre-B cells (pre-B ALL) is the most frequent form of leukemia affecting children in Western countries. Evidence is accumulating that genetic factors play an important role in conferring susceptibility/resistance to leukemia in children. In this regard, activating killer-cell immunoglobulin-like receptor (KIR) genes are of particular interest. Humans may inherit different numbers of the 6 distinct activating KIR genes. Little is known about the impact of this genetic variation on the innate susceptibility or resistance of humans to the development of B-ALL. We addressed this issue by performing a case-control study in Canadian children of white origin. Our results show that harboring activating KIR genes is associated with reduced risk for developing B-ALL in these children. Of the 6 activating KIR genes, KIR2DS2 was maximally associated with decreased risk for the disease (P = 1.14 × 10−7). Furthermore, our results showed that inheritance of a higher number of activating KIR genes was associated with significant reductions in risk for ALL in children. These results were also consistent across different ALL phenotypes, which included children with pre-T cell ALL. Our study provides novel insights concerning the pathogenesis of childhood leukemia in white children and has implications for the development of new immunotherapies for this cancer.
Musashi 2 is a regulator of the HSC compartment identified by a retroviral insertion screen and knockout mice
Authors: de Andrés-Aguayo Luisa , Varas Florencio , Kallin Eric M. , Infante José F. , Wurst Wolfgang , Floss Thomas , Graf Thomas 
Published: May 2011

Abstract
We used a retroviral integration screen to search for novel genes that regulate HSC function. One of the genes that conferred HSC dominance when overexpressed due to an adjacent retroviral insertion was Musashi 2 (Msi2), an RNA-binding protein that can act as a translational inhibitor. A gene-trap mouse model that inactivates the gene shows that Msi2 is more highly expressed in long-term (LT) and short-term (ST) HSCs, as well as in lymphoid myeloid primed progenitors (LMPPs), but much less in intermediate progenitors and mature cells. Mice lacking Msi2 are fully viable for up to a year or more, but exhibit severe defects in primitive precursors, most significantly a reduction in the number of ST-HSCs and LMPPs and a decrease in leukocyte numbers, effects that are exacerbated with age. Cell-cycle and gene-expression analyses suggest that the main hematopoietic defect in Msi2-defective mice is the decreased proliferation capacity of ST-HSCs and LMPPs. In addition, HSCs lacking Msi2 are severely impaired in competitive repopulation experiments, being overgrown by wild-type cells even when mutant cells were provided in excess. Our data indicate that Msi2 maintains the stem cell compartment mainly by regulating the proliferation of primitive progenitors downstream of LT-HSCs.
The only proposed T-cell epitope derived from the TEL-AML1 translocation is not naturally processed
Authors: Popović Jelena , Li Liang-Ping , Kloetzel Peter Michael , Leisegang Matthias , Uckert Wolfgang , Blankenstein Thomas 
Published: May 2011

AbstractAdoptive therapy with T-cell receptor (TCR)–engineered T cells is a promising approach in cancer treatment. While usage of T cells specific for tumor-associated antigens (TAAs) can lead to serious side effects because of autoimmunity, targeting true tumor-specific mutations, such as the products of translocations in leukemias, should reduce such a risk. A potentially ideal target might be the chimeric protein TEL-AML1, which results from the chromosomal translocation 12;21 and represents the most common fusion gene in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Within the fusion region of TEL-AML1, a single epitope has been described by reverse immunology as immunogenic in HLA-A*0201 restriction settings. As a potential source of TCRs specific for this TEL-AML1 epitope, we have used mice expressing a human TCR-αβ repertoire and human MHC class I. Surprisingly, we have found that, although a specific functional CD8+ T-cell response against this peptide could be evoked, the described epitope was in fact not endogenously processed. Analyses done with a potent antigen-presenting cell line, as well as with purified human proteasomes, support the conclusion that this peptide cannot be proposed as a potential target in immunotherapy of ALL in HLA-A*0201-restricted fashion.
Missense mutations in PML-RARA are critical for the lack of responsiveness to arsenic trioxide treatment
Authors: Goto Emi , Tomita Akihiro , Hayakawa Fumihiko , Atsumi Akihide , Kiyoi Hitoshi , Naoe Tomoki 
Published: May 2011

AbstractArsenic trioxide (As2O3) is a highly effective treatment for patients with refractory/relapsed acute promyelocytic leukemia (APL), but resistance to As2O3 has recently been seen. In the present study, we report the findings that 2 of 15 patients with refractory/relapsed APL treated with As2O3 were clinically As2O3 resistant. Leukemia cells from these 2 patients harbored missense mutations in promyelocytic leukemia gene–retinoic acid receptor-α gene (PML-RARA) transcripts, resulting in amino acid substitutions of A216V and L218P in the PML B2 domain. When wild-type or mutated PML-RARA (PR-WT and PR-B/L-mut, respectively) were overexpressed in HeLa cells, immunoblotting showed SUMOylated and/or oligomerized protein bands in PR-WT but not in PR-B/L-mut after As2O3 treatment. Protein-localization analysis indicated that PR-WT in the soluble fraction was transferred to the insoluble fraction after treatment with As2O3, but PR-B/L-mut was stably detected in fractions both with and without As2O3. Immunofluorescent microscopy analysis showed PR-WT localization as a microgranular pattern in the cytoplasm without As2O3 and as a macrogranular pattern with As2O3. PR-B/L-mut was diffusely observed in the cytoplasm with and without As2O3. Nearly identical localization patterns were observed in patients' primary cells. Therefore, B2 domain mutations may play an important role in aberrant molecular responses to As2O3 and may be critical for As2O3 resistance in APL.
High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia
Authors: Leung Wing , Campana Dario , Yang Jie , Pei Deqing , Coustan-Smith Elaine , Gan Kwan , Rubnitz Jeffrey E. , Sandlund John T. , Ribeiro Raul C. , Srinivasan Ashok , Hartford Christine , Triplett Brandon M. , Dallas Mari , Pillai Asha , Handgretinger Rupert , Laver Joseph H. , Pui Ching-Hon 
Published: May 2011

AbstractWe evaluated 190 children with very high-risk leukemia, who underwent allogeneic hematopoietic cell transplantation in 2 sequential treatment eras, to determine whether those treated with contemporary protocols had a high risk of relapse or toxic death, and whether non–HLA-identical transplantations yielded poor outcomes. For the recent cohorts, the 5-year overall survival rates were 65% for the 37 patients with acute lymphoblastic leukemia and 74% for the 46 with acute myeloid leukemia; these rates compared favorably with those of earlier cohorts (28%, n = 57; and 34%, n = 50, respectively). Improvement in the recent cohorts was observed regardless of donor type (sibling, 70% vs 24%; unrelated, 61% vs 37%; and haploidentical, 88% vs 19%), attributable to less infection (hazard ratio [HR] = 0.12; P = .005), regimen-related toxicity (HR = 0.25; P = .002), and leukemia-related death (HR = 0.40; P = .01). Survival probability was dependent on leukemia status (first remission vs more advanced disease; HR = 0.63; P = .03) or minimal residual disease (positive vs negative; HR = 2.10; P = .01) at the time of transplantation. We concluded that transplantation has improved over time and should be considered for all children with very high-risk leukemia, regardless of matched donor availability.
Anti-CD45 pretargeted radioimmunotherapy using bismuth-213: high rates of complete remission and long-term survival in a mouse myeloid leukemia xenograft model
Authors: Pagel John M. , Kenoyer Aimee L. , Bäck Tom , Hamlin Donald K. , Wilbur D. Scott , Fisher Darrell R. , Park Steven I. , Frayo Shani , Axtman Amanda , Orgun Nural , Orozco Johnnie , Shenoi Jaideep , Lin Yukang , Gopal Ajay K. , Green Damian J. , Appelbaum Frederick R. , Press Oliver W. 
Published: May 2011

Abstract
Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)–streptavidin (SA) conjugate and DOTA-biotin labeled with β-emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. α-emitting radionuclides exhibit high cytotoxicity coupled with a short path length, potentially increasing the therapeutic index and making them an attractive alternative to β-emitting radionuclides for patients with acute myeloid leukemia. Accordingly, we have used 213Bi in mice with human leukemia xenografts. Results demonstrated excellent localization of 213Bi-DOTA-biotin to tumors with minimal uptake into normal organs. After 10 minutes, 4.5% ± 1.1% of the injected dose of 213Bi was delivered per gram of tumor. α-imaging demonstrated uniform radionuclide distribution within tumor tissue 45 minutes after 213Bi-DOTA-biotin injection. Radiation absorbed doses were similar to those observed using a β-emitting radionuclide (90Y) in the same model. We conducted therapy experiments in a xenograft model using a single-dose of 213Bi-DOTA-biotin given 24 hours after anti-CD45 Ab-SA conjugate. Among mice treated with anti-CD45 Ab-SA conjugate followed by 800 μCi of 213Bi- or 90Y-DOTA-biotin, 80% and 20%, respectively, survived leukemia-free for more than 100 days with minimal toxicity. These data suggest that anti-CD45 PRIT using an α-emitting radionuclide may be highly effective and minimally toxic for treatment of acute myeloid leukemia.
Characterization of the expression, promoter activity and molecular architecture of fibin
Authors: Lakner Johannes , Seyer Christian , Hermsdorf Thomas , Schöneberg Torsten 
Published: May 2011

Abstract

Background
Fibin was initially discovered as a secreted signal molecule essential for pectoral fin bud initiation in zebrafish. Currently, there is little information about the molecular architecture and biological relevance of fibin in humans and other mammals.

Results
Fibin is expressed in cerebellum, skeletal muscle and many other embryonic and adult mouse tissues suggesting not only a role during embryonic development but also in adult functions. A 2.5-kbp genomic sequence fragment upstream of the coding sequence is sufficient to drive and regulate fibin expression through stimulation by glucocorticoids, activators of the protein kinase C signalling pathways and manganese ions. Fibin is an evolutionarily conserved protein, carries a cleavable signal peptide (amino acids 1-18) and is glycosylated at Asn30. The two conserved cysteines participate in intermolecular disulfide bond and multimer formation. Although fibin displays all features of a secretory protein, it is mostly retained in the endoplasmic reticulum when heterologously expressed.

Conclusion
Fibin is functionally relevant during embryogenesis and adult life. Its expression is regulated by a number of cellular signalling pathways and the protein is routed via the secretory pathway. However, proper secretion presumably requires an unknown covalently-linked or associated co-factor.
Protein coalitions in a core mammalian biochemical network linked by rapidly evolving proteins
Authors: Ainali Chrysanthi , Simon Michelle , Freilich Shiri , Espinosa Octavio , Hazelwood Lee , Tsoka Sophia , Ouzounis Christos A , Hancock John M 
Published: May 2011

Abstract

Background
Cellular ATP levels are generated by glucose-stimulated mitochondrial metabolism and determine metabolic responses, such as glucose-stimulated insulin secretion (GSIS) from the β-cells of pancreatic islets. We describe an analysis of the evolutionary processes affecting the core enzymes involved in glucose-stimulated insulin secretion in mammals. The proteins involved in this system belong to ancient enzymatic pathways: glycolysis, the TCA cycle and oxidative phosphorylation.

Results
We identify two sets of proteins, or protein coalitions, in this group of 77 enzymes with distinct evolutionary patterns. Members of the glycolysis, TCA cycle, metabolite transport, pyruvate and NADH shuttles have low rates of protein sequence evolution, as inferred from a human-mouse comparison, and relatively high rates of evolutionary gene duplication. Respiratory chain and glutathione pathway proteins evolve faster, exhibiting lower rates of gene duplication. A small number of proteins in the system evolve significantly faster than co-pathway members and may serve as rapidly evolving adapters, linking groups of co-evolving genes.

Conclusions
Our results provide insights into the evolution of the involved proteins. We find evidence for two coalitions of proteins and the role of co-adaptation in protein evolution is identified and could be used in future research within a functional context.
Analysis of common bean expressed sequence tags identifies sulfur metabolic pathways active in seed and sulfur-rich proteins highly expressed in the absence of phaseolin and major lectins
Authors: Yin Fuqiang , Pajak Agnieszka , Chapman Ralph , Sharpe Andrew , Huang Shangzhi , Marsolais Frédéric 
Published: May 2011

Abstract

Background
A deficiency in phaseolin and phytohemagglutinin is associated with a near doubling of sulfur amino acid content in genetically related lines of common bean (Phaseolus vulgaris), particularly cysteine, elevated by 70%, and methionine, elevated by 10%. This mostly takes place at the expense of an abundant non-protein amino acid, S-methyl-cysteine. The deficiency in phaseolin and phytohemagglutinin is mainly compensated by increased levels of the 11S globulin legumin and residual lectins. Legumin, albumin-2, defensin and albumin-1 were previously identified as contributing to the increased sulfur amino acid content in the mutant line, on the basis of similarity to proteins from other legumes.

Results
Profiling of free amino acid in developing seeds of the BAT93 reference genotype revealed a biphasic accumulation of gamma-glutamyl-S-methyl-cysteine, the main soluble form of S-methyl-cysteine, with a lag phase occurring during storage protein accumulation. A collection of 30,147 expressed sequence tags (ESTs) was generated from four developmental stages, corresponding to distinct phases of gamma-glutamyl-S-methyl-cysteine accumulation, and covering the transitions to reserve accumulation and dessication. Analysis of gene ontology categories indicated the occurrence of multiple sulfur metabolic pathways, including all enzymatic activities responsible for sulfate assimilation, de novo cysteine and methionine biosynthesis. Integration of genomic and proteomic data enabled the identification and isolation of cDNAs coding for legumin, albumin-2, defensin D1 and albumin-1A and -B induced in the absence of phaseolin and phytohemagglutinin. Their deduced amino acid sequences have a higher content of cysteine than methionine, providing an explanation for the preferential increase of cysteine in the mutant line.

Conclusion
The EST collection provides a foundation to further investigate sulfur metabolism and the differential accumulation of sulfur amino acids in seed of common bean. Identification of sulfur-rich proteins whose levels are elevated in seed lacking phaseolin and phytohemagglutinin and sulfur metabolic genes may assist the improvement of protein quality.