bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomical Balance of the Upper Airway and Obstructive Sleep Apnea
Authors: Tsuiki Satoru , Isono Shiroh , Ishikawa Teruhiko , Yamashiro Yoshihiro , Tatsumi Koichiro , Nishino Takashi 
Published: May 2008

Background
Obesity and craniofacial abnormalities such as small maxilla and mandible are common features of patients with obstructive sleep apnea (OSA). The authors hypothesized that anatomical imbalance between the upper airway soft-tissue volume and the craniofacial size (rather than each alone) may result in pharyngeal airway obstruction during sleep, and therefore development of OSA.

Methods
Blind measurements of tongue cross-sectional area and craniofacial dimensions were performed through lateral cephalograms in 50 adult male patients with OSA and 55 adult male non-OSA subjects with various craniofacial dimensions.

Results
Maxillomandibular dimensions were matched between OSA and non-OSA groups. While the tongue was significantly larger in subjects with larger maxillomandible dimensions, OSA patients had a significantly larger tongue for a given maxillomandible size than non-OSA subjects. The hypothesis was also supported in subgroups matched for both body mass index and maxillomandible dimensions.

Conclusions
Upper airway anatomical imbalance is involved in the pathogenesis of OSA.
Trans-activator of Transcription-mediated Delivery of NEP1-40 Protein into Brain Has a Neuroprotective Effect against Focal Cerebral Ischemic Injury via Inhibition of Neuronal Apoptosis
Authors: Wang Qiang , Gou Xingchun , Xiong Lize , Jin Weilin , Chen Shaoyang , Hou Lichao , Xu Lixian 
Published: May 2008

Background
The Nogo-66 antagonistic peptide (NEP1-40) is a potential candidate for therapeutic intervention of neuronal injury. However, delivery of the proteins across the blood-brain barrier is severely limited by its size and biochemical properties. The current study was designed to evaluate the transducible effects of the trans-activator of transcription (TAT) transduction system for NEP1-40 to cross the blood-brain barrier and to clarify whether intraperitoneal administration of TAT-NEP1-40 could protect cerebral neurons from ischemic injury.

Methods
Adult male Sprague-Dawley rats were submitted to a 120-min focal ischemia and received an intraperitoneal injection of No-TAT-NEP1-40, TAT-NEP1-40, TAT-beta-galactosidase, or vehicle. The existence of the proteins in the brain was analyzed with immunofluorescence and Western blot techniques at 6 h after injection. Brain ischemic injury was evaluated by neurologic deficit scores, infarction volumes, terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling staining, and assay of caspase-3 activity.

Results
Western blot analysis and immunofluorescence staining confirmed the presence of TAT-NEP1-40 protein in the brains 6 h after injection. Intraperitoneal injection of TAT-NEP1-40 could attenuate the numbers of terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling-positive cells and activated caspase-3 positive cells, and increase the viability of the cells in the ischemic bounder zone, compared with that treated with No-TAT-NEP1-40, TAT-beta-Gal, or vehicle. Furthermore, treatment with TAT-NEP1-40 significantly improved the neurologic outcomes and reduced the size of the infarction in rats.

Conclusions
The results demonstrate that the TAT-NEP1-40 could be efficiently delivered into the rat brains and improve ischemia-induced neurologic outcomes through attenuating cell apoptosis in ischemic brains.
Effect of Nitrous Oxide on Neuronal Damage and Extracellular Glutamate Concentration as a Function of Mild, Moderate, or Severe Ischemia in Halothane-anesthetized Gerbils
Authors: Taninishi Hideki , Takeda Yoshimasa , Kobayashi Motomu , Sasaki Toshihiro , Arai Minako , Morita Kiyoshi 
Published: May 2008

Background
The effect of nitrous oxide on ischemic neuronal damage was quantitatively evaluated by use of logistic regression curves.

Methods
Seventy-two gerbils were anesthetized with 1% halothane and randomly assigned to receive 70% nitrous oxide or 70% nitrogen. Forebrain ischemia was performed for 3, 5, or 7 min, and direct-current potential in the hippocampal CA1 region was recorded. Histologic outcome was evaluated 5 days later. Relations of neuronal damage with ischemic duration and duration of ischemic depolarization were determined by logistic regression curves. In some animals, extracellular glutamate concentration was measured every 60 s during forebrain ischemia.

Results
Nitrous oxide increased neuronal damage only with 5 min of ischemia (nitrous oxide vs. nitrogen: 78.5 +/- 23.0 vs. 37.3 +/- 12.2%; P < 0.01). The percentages of neuronal damage with 3 and 7 min of ischemia were not different with or without nitrous oxide. Logistic regression curves indicated that nitrous oxide significantly increased neuronal damage during the period from 3.07 to 6.63 min of ischemia. Logistic regression curves also indicated that nitrous oxide increased neuronal damage in the condition of the same duration of ischemic depolarization. Nitrous oxide shortened the ischemic duration necessary for causing 50% neuronal damage by 0.82 min. Dynamic change in extracellular glutamate concentration was not different (mean maximum dialysate glutamate concentration: 4.29 +/- 3.09 vs. 4.63 +/- 1.83 microm).

Conclusion
Administration of nitrous oxide caused an increase in ischemic neuronal damage, but a significant adverse effect was observed with a limited range of ischemic intervals.
Genetic variation within the Lidia bovine breed
Authors: Cañón J. , Tupac‐Yupanqui I. , García‐Atance M. A. , Cortés O. , García D. , Fernández J. , Dunner S. 
Published: May 2008

SummaryThe results of an exhaustive data collection from a bovine population with a low level of exchangeability, the Lidia breed, are presented. A total of 1683 individuals from 79 herds were sampled and genetic diversity within and among lineages was assessed using 24 microsatellite loci on 22 different chromosomes. Expected heterozygosity ranged between 0.46 and 0.68 per lineage and there was significant inbreeding in the lineages, which included several farms [mean FIS = 0.11, bootstrap 95% confidence interval (0.09, 0.14)], mainly because of the high genetic divergence between herds within those lineages. High genetic differentiation between lineages was also found with a mean FST of 0.18 [bootstrap 95% confidence interval (0.17, 0.19)], and all pairwise values, which ranged from 0.07 to 0.35, were highly significant. The relationships among lineages showed weak statistical support. Nonetheless, lineages were highly discrete when analysed using correspondence analysis and a great proportion of the individuals were correctly assigned to their own lineage when performing standard assignment procedures.
The novel bispecific diabody αCD40/αCD28 strengthens leukaemic dendritic cell‐induced T‐cell reactivity
Authors: Houtenbos Ilse , Santegoets Saskia , Westers Theresia M. , Waisfisz Quinten , Kipriyanov Sergey , Denkers Fedor , Scheper Rik J. , De Gruijl Tanja D. , Ossenkoppele Gert J. , Van De Loosdrecht Arjan A. 
Published: May 2008

SummaryDendritic cell (DC)‐based immunotherapy faces new challenges because the efficacy of DC vaccines in clinical trials has been inconsistent. Strategies to improve immune responses induced by DC are currently being explored. We have recently shown the feasibility of generating fully functional DC from acute myeloid leukaemic (AML) blasts, but with varying expression levels of the important costimulatory molecule CD86. To overcome this variability, we developed a novel bispecific diabody that simultaneously and agonistically targeted CD40 on AML‐DC and CD28 on naïve T cells. Beside optimization of CD28‐mediated signalling, the resulting cellular cross‐linking was also hypothesized to increase the strength and duration of T cell/AML‐DC interactions, thus increasing T‐cell responsiveness to AML antigens. The αCD40/αCD28‐bispecific diabody was found to bind to its target antigens and provoked increased T‐cell–DC cluster formation. The αCD40/αCD28 diabody is capable of increasing T‐cell proliferation induced by AML‐DC as well as the induction of DC maturation. Importantly, priming efficacy of tumour‐specific cytotoxic T cells can also be improved by cross‐linking AML‐DC and T cells with the αCD40/αCD28 diabody. We propose that the αCD40/αCD28‐bispecific diabody can serve as a potent therapeutic tool to effectively augment anti‐tumour T‐cell responses elicited by AML‐DC.
Thromboelastography in children with coagulation factor deficiencies
Authors: Chitlur Meera , Warrier Indira , Rajpurkar Madhvi , Hollon Wendy , Llanto Lolita , Wiseman Carol , Lusher Jeanne M. 
Published: May 2008

SummaryHemophilia is traditionally classified according to the levels of the deficient coagulation factor as Severe (<1%), Moderate (1–5%) or Mild (>5%). However, it is well known that the factor activity does not necessarily correspond to the clinical bleeding manifestations. As prophylactic therapy is the best method of prevention of serious complications such as hemophilic arthropathy, a test that may predict the bleeding pattern would be extremely beneficial. Thromboelastography (TEG) uses whole blood to determine clot formation characteristics, such as initiation, propagation as well as strength of the clot, and is now being extensively studied in bleeding and thrombophilia. This study attempted to determine the TEG characteristics in 47 children with moderate hemophilia (MH) and severe hemophilia with (SHI) and without inhibitors (SH) and tried to retrospectively correlate them to the clinical bleeding patterns. TEG showed evidence of faster and better clot formation, as evidenced by a higher maximum thrombin/fibrin generation, in those with mild bleeding manifestations compared to those with severe bleeding tendency, in addition to the expected prolongation in time to formation of clot related to factor deficiency. This may be a potentially useful tool to evaluate the bleeding tendency and determine need for prophylaxis in children with hemophilia.
Treosulfan‐containing regimens achieve high rates of engraftment associated with low transplant morbidity and mortality in children with non‐malignant disease and significant co‐morbidities
Authors: Greystoke Brigit , Bonanomi Sonia , Carr Trevor F. , Gharib Maged , Khalid Tasneem , Coussons Mary , Jagani Mamta , Naik Paru , Rao Kanchana , Goulden Nicholas , Amrolia Persis , Wynn Robert F. , Veys Paul A. 
Published: May 2008

SummaryTreosulfan is an immuno‐suppressive and myeloablative alkylating agent that has been introduced as a conditioning agent in stem cell transplantation (SCT). Most studies have been performed in adult patients with malignancy where a low incidence of regimen‐related toxicity has been reported. We report the use of treosulfan in 32 consecutive children undergoing SCT for non‐malignant disease. Patients received a total treosulfan dose of 36 or 42 g/m2/patient given in three daily, divided doses. A range of other conditioning agents and serotherapy was administered to patients who underwent family donor SCT (n = 11), or unrelated donor SCT (n = 21). One patient (3%) died early. Transplant morbidity was limited and mucositis was only mild. Dermatological toxicity was frequent but mild. Twenty‐eight patients (87·5%) established donor cell engraftment. In 25 patients (78%) there was adequate, stable donor engraftment. Four patients have required additional transplant procedures to maintain adequate donor‐derived haemopoiesis. Twenty‐seven patients (84%) survive with a median follow up of 417 d. There were four late deaths due to progression of the underlying disease, graft‐versus‐host disease or infection. Treosulfan‐based conditioning regimens achieve excellent engraftment with reduced regimen‐related toxicity in children with non‐malignant disease at high risk for both regimen‐related toxicity and graft failure.
Ocular adnexal lymphoma: no evidence for bacterial DNA associated with lymphoma pathogenesis
Authors: Matthews Julie M. , Moreno Lilliana I. , Dennis Jeremy , Byrne Gerald E. , Ruiz Phillip , Dubovy Sander R. , Lossos Izidore S. 
Published: May 2008

SummaryOcular Adnexal Lymphomas (OALs) are the most common tumors of the eye, the majority being extranodal mucosa‐associated lymphoid tissue (MALT) lymphomas. Association with Chlamydia psittaci was described in some geographic areas. OAL response to antibiotic therapy was reported in cases not harboring Chlamydia psittaci DNA, suggesting that other bacterial infection might be implicated in the pathogenesis. We examined 49 MALT OALs for bacterial DNA using two distinct polymerase chain reaction techniques based on universal bacterial primers. No bacterial DNA that could be implicated in OAL pathogenesis was detected, suggesting that bacterial infection is not associated with OAL in South Florida.
TGF‐β receptor kinase inhibitor LY2109761 reverses the anti‐apoptotic effects of TGF‐β1 in myelo‐monocytic leukaemic cells co‐cultured with stromal cells
Authors: Xu Yuanyuan , Tabe Yoko , Jin Linhua , Watt Julie , McQueen Teresa , Ohsaka Akimichi , Andreeff Michael , Konopleva Marina 
Published: May 2008

SummaryTransforming growth factor β1 (TGF‐β1) is an essential regulator of cell proliferation, survival and apoptosis, depending on the cellular context. TGF‐β1 is also known to affect cell‐to‐cell interactions between tumour cells and stromal cells. We investigated the role of TGF‐β1 in the survival of myelo‐monocytic leukaemia cell lines co‐cultured with bone marrow (BM)‐derived mesenchymal stem cells (MSC). Treatment with recombinant human (rh)TGF‐β1 inhibited spontaneous and cytarabine‐induced apoptosis in U937 cells, most prominently in U937 cells directly attached to MSCs. Conversely, the pro‐survival effects of TGF‐β1 were inhibited by LY2109761 or TGF‐β1 neutralizing antibody. rhTGF‐β1 increased pro‐survival phosphorylation of Akt, which was inhibited by LY2109761. The combination of rhTGF‐β1 and MSC co‐culture induced significant upregulation of C/EBPβ gene (CEBPB) and protein expression along with increased C/EBPβ liver‐enriched activating protein: liver‐enriched inhibitory protein ratio, suggesting the novel role of C/EBPβ in TGF‐β1‐mediated U937 cell survival in the context of stromal cell support. In summary, these results indicate that TGF‐β1 produced by BM stromal cells promotes the survival and chemoresistance of leukaemia cells under the direct cell‐to‐cell interactions. The blockade of TGF‐β signalling by LY2109761, which effectively inhibited the pro‐survival signalling, may enhance the efficacy of chemotherapy against myelo‐monocytic leukaemic cells in the BM microenvironment.
Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome
Authors: Rossi Davide , Cerri Michaela , Capello Daniela , Deambrogi Clara , Rossi Francesca Maria , Zucchetto Antonella , De Paoli Lorenzo , Cresta Stefania , Rasi Silvia , Spina Valeria , Franceschetti Silvia , Lunghi Monia , Vendramin Chiara , Bomben Riccardo , Ramponi Antonio , Monga Guido , Conconi Annarita , Magnani Corrado , Gattei Valter , Gaidano Gianluca 
Published: May 2008

SummaryPredictors of chronic lymphocytic leukaemia (CLL) transformation to Richter syndrome (RS) are not established and were investigated in 185 consecutive CLL cases. Actuarial incidence of RS (n = 17; all diffuse large B‐cell lymphomas) at 10 years was 16·2% (95% confidence interval: 8·0–24·4%). At CLL diagnosis, prognosticators of RS by univariate analysis wereIGHVhomology ≥98% (P = 0·006),IGHV4‐39usage (P < 0·001), del13q14 absence (P = 0·004), expression of CD38 (P < 0·001) and ZAP70 (P = 0·004), size (P < 0·001) and number (P < 0·001) of lymph nodes, advanced Binet stage (P = 0·002), and lactate dehydrogenase (P < 0·001). Multivariate analysis, performed separately for biological and clinical variables, identified CD38 expression [Hazard ratio (HR) = 4·26;P = 0·018],IGHV4‐39usage (HR = 4·29;P = 0·018), and lymph node size ≥3 cm (HR = 9·07;P < 0·001) as independent RS prognosticators. A multivariate model simultaneously analysing biological and clinical variables identified lymph node size ≥3 cm (HR = 6·51;P = 0·001) and del13q14 absence (HR = 4·08;P = 0·031) as independent RS prognosticators. Risk factors of CLL transformation differed from risk factors of CLL progression. These results suggest that CD38 and del13q14 may identify biological subsets of CLL with different RS predisposition. Predominant nodal disease, CD38 expression,IGHV4‐39usage, and absence of del13q14 may help in predicting RS at CLL diagnosis. Close monitoring and a careful biopsy policy are needed in patients carrying transformation risk factors.
Splenic marginal zone lymphomas are characterized by loss of interstitial regions of chromosome 7q, 7q31.32 and 7q36.2 that include the protection of telomere 1 (POT1) and sonic hedgehog (SHH) genes
Authors: Vega Francisco , Cho‐Vega Jeong Hee , Lennon Patrick A. , Luthra Madan G. , Bailey Jaime , Breeden Megan , Jones Dan , Medeiros L. Jeffrey , Luthra Rajyalakshmi 
Published: May 2008

SummaryTo further characterize the genotypic features of splenic (S) and nodal (N) marginal zone lymphomas (MZL) we compared eight SMZL and five NMZL by array‐based comparative genomic hybridization (aCGH). Arbitrarily, aberrations were divided into major imbalances, defined as gains or losses involving five or more contiguous genetic loci, and minor imbalances, defined as those involving four or fewer loci. SMZL, but not NMZL, demonstrated major imbalances. These included deletions involving various lengths of 7q (three cases), and 14q23q24 (one case) and gains of 9p13p21 (one case), 13q21q33 (one case) and 16p13.1 (one case). Common minor imbalances in SMZL were: loss of sonic hedgehog gene (SHH) at 7q36.2 (four cases), loss of protection of telomere 1 gene (POT1) at 7q31.32 (three cases), and gain of glioma associated oncogene 1 (GLI1) at 12q13.2 (three cases). Common minor alterations in NMZL were: loss of the fas‐associated via death domain gene (FADD) at 11q13.2 (three cases) and gain of GLI1 (five cases). In conclusion, SMZL, but not NMZL, demonstrates large genomic imbalances and frequent loss of the 7q31.32 and 7q36.2 regions involving POT1 and SHH, respectively. In NMZL, loss of FADD and gain of GLI1 are frequent events.
Treosulfan and fludarabine low‐toxicity conditioning for allogeneic haematopoietic stem cell transplantation in chronic myeloid leukaemia
Authors: Holowiecki Jerzy , Giebel Sebastian , Wojnar Jerzy , Krawczyk‐Kulis Malgorzata , Markiewicz Miroslaw , Holowiecka‐Goral Aleksandra , Freund Mathias , Casper Jochen 
Published: May 2008

SummaryAllogeneic haematopoietic stem cell transplantation (alloHSCT) is the only treatment of proven long‐term efficacy in chronic myeloid leukaemia (CML), although high non‐relapse mortality (NRM) observed after conventional myeloablative conditioning limits its applicability. This phase II trial evaluated the efficacy and toxicity of a new preparative regimen consisting of treosulfan 3 × 14 g/m2 and fludarabine 5 × 30 mg/m2, in patients with CML in chronic phase. Among the 40 patients included, 18 received alloHSCT from a sibling and 22 from an unrelated donor. All patients engrafted with 92·5% of cases achieving complete donor chimaerism by day +100. All but one patient had achieved complete cytogenetic remission on day +100. Grade III or IV non‐haematological toxicities included: neutropenic fever (10%), nausea/vomiting (10%), elevated liver enzymes (5%) and infection (2·5%). The incidence of grade II–IV acute graft‐versus‐host disease (GVHD) was 22·5% and extensive chronic GVHD, 14%. The 2‐year probability of overall survival, leukaemia‐free survival and NRM was 85%, 82·5% and 15% respectively. At 1 year post‐transplant, 85% of survivors had a Karnofsky index of 100%. We concluded that treosulfan and fludarabine conditioning is a low‐toxicity regimen with high anti‐leukaemic potential that seems feasible in CML patients referred for alloHSCT.
Status of minimal residual disease after induction predicts outcome in both standard and high‐risk Ph‐negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4‐2002 MRD Study
Authors: Holowiecki Jerzy , Krawczyk‐Kulis Malgorzata , Giebel Sebastian , Jagoda Krystyna , Stella‐Holowiecka Beata , Piatkowska‐Jakubas Beata , Paluszewska Monika , Seferynska Ilona , Lewandowski Krzysztof , Kielbinski Marek , Czyz Anna , Balana‐Nowak Agnieszka , Król Maria , Skotnicki Aleksander B. , Jedrzejczak Wieslaw W. , Warzocha Krzysztof , Lange Andrzej , Hellmann Andrzej 
Published: May 2008

SummaryThe treatment of adults with Philadelphia‐negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4‐2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17–60 years), 116 patients were suitable for analysis. MRD level ≥0·1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population (P < 0·0001), as well as in the standard risk (SR,P = 0·0003) and high‐risk (P = 0·008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0·1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects (P = 0·001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.
Germinal center B (GCB) and non‐GCB cell‐like diffuse large B cell lymphomas have similar outcomes following autologous haematopoietic stem cell transplantation
Authors: Costa Luciano J. , Feldman Andrew L. , Micallef Ivana N. , Inwards David J. , Johnston Patrick B. , Porrata Luis F. , Ansell Stephen M. 
Published: May 2008

SummaryPatients with germinal center B cell‐like (GCB) and non‐GCB diffuse large B cell lymphomas (DLBCL) receiving first line therapy have distinct prognosis. We explored the differences in outcome following salvage autologous hematopoietic stem cell (HSC) transplantation between patients with GCB and non‐GCB DLBCL. Forty‐four patients with relapsed and 15 patients with primary refractory chemosensitive disease undergoing BEAM (BCNU [carmustine], etoposide, cytarabine, melphalan) conditioning and autologous HSC were included. Immunohistochemical analysis was performed for CD10, BCL‐6, MUM1 (allowing classification into GCB and non‐GCB‐like DLBCL) and BCL‐2. Median follow‐up of survivors was 25 months; median age at the time of transplantation was 60 years (range 17–77). Thirty‐two patients (54%) were classified as having GCB and 27 (46%) as having non‐GCB‐like DLBCL. Patients with GCB and non‐GCB DLBCL did not differ in the risk of progression after HSC transplant (P = 0·78) or overall survival (P = 0·48). In multivariate analysis, only time to progression after initial treatment impacted overall survival. We conclude that patients with relapsed or primary refractory chemosensitive GCB and non‐GCB‐like DLBCL derive similar benefit from autologous HSC transplant.