bluuebunny/crossref_metadata_2025_split huggingface dataset:
Boundary cap cells constrain spinal motor neuron somal migration at motor exit points by a semaphorin-plexin mechanism
Authors: Bron Romke , Vermeren Matthieu , Kokot Natalie , Andrews William , Little Graham E , Mitchell Kevin J , Cohen James 
Published: October 2007

Abstract
Background
In developing neurons, somal migration and initiation of axon outgrowth often occur simultaneously and are regulated in part by similar classes of molecules. When neurons reach their final destinations, however, somal translocation and axon extension are uncoupled. Insights into the mechanisms underlying this process of disengagement came from our study of the behaviour of embryonic spinal motor neurons following ablation of boundary cap cells. These are neural crest derivatives that transiently reside at motor exit points, central nervous system (CNS):peripheral nervous system (PNS) interfaces where motor axons leave the CNS. In the absence of boundary cap cells, motor neuron cell bodies migrate along their axons into the periphery, suggesting that repellent signals from boundary cap cells regulate the selective gating of somal migration and axon outgrowth at the motor exit point. Here we used RNA interference in the chick embryo together with analysis of null mutant mice to identify possible boundary cap cell ligands, their receptors on motor neurons and cytoplasmic signalling molecules that control this process.

Results
We demonstrate that targeted knock down in motor neurons of Neuropilin-2 (Npn-2), a high affinity receptor for class 3 semaphorins, causes their somata to migrate to ectopic positions in ventral nerve roots. This finding was corroborated in Npn-2 null mice, in which we identified motor neuron cell bodies in ectopic positions in the PNS. Our RNA interference studies further revealed a role for Plexin-A2, but not Plexin-A1 or Plexin-A4. We show that chick and mouse boundary cap cells express Sema3B and 3G, secreted semaphorins, and Sema6A, a transmembrane semaphorin. However, no increased numbers of ectopic motor neurons are found in Sema3B null mouse embryos. In contrast, Sema6A null mice display an ectopic motor neuron phenotype. Finally, knockdown of MICAL3, a downstream semaphorin/Plexin-A signalling molecule, in chick motor neurons led to their ectopic positioning in the PNS.

Conclusion
We conclude that semaphorin-mediated repellent interactions between boundary cap cells and immature spinal motor neurons regulates somal positioning by countering the drag exerted on motor neuron cell bodies by their axons as they emerge from the CNS at motor exit points. Our data support a model in which BC cell semaphorins signal through Npn-2 and/or Plexin-A2 receptors on motor neurons via a cytoplasmic effector, MICAL3, to trigger cytoskeletal reorganisation. This leads to the disengagement of somal migration from axon extension and the confinement of motor neuron cell bodies to the spinal cord.
Community-acquired Klebsiella pneumoniae meningitis in an alcoholic patient with an infected pancreatic pseudocyst; a case report and review of literature
Authors: Orzechowska Adriana , Lacey Sandra , Soosay Geraldine , Melzer Mark 
Published: October 2007

Abstract
We report a case of a 49-year-old male with a history of chronic alcoholism and evidence of a pancreatic pseudocyst on CT scanning. He presented with a 3-days history of fever, loss of appetite and upper abdominal pain. Blood cultures grew Klebsiella pneumoniae and he improved clinically with a seven-day course of intravenous co-amoxiclav and metronidazole. Two weeks later he was readmitted to hospital with impaired consciousness and septic shock, and died three days later in intensive care. Post mortem examination revealed bacterial meningitis and an infected pancreatic pseudocyst. Klebsiella pneumoniae was isolated from the pancreas and meninges.
Atypical haemolytic uraemic syndrome presenting initially as suspected meningococcal disease: a case report
Authors: Sivamurthy Siddharthan , Mooney John D , Kenny Tom D 
Published: October 2007

Abstract

Background
Haemolytic uraemic syndrome (HUS) is the most common cause of acute renal failure in children and is usually linked with Escherichia coli O157 infection. With a fatality rate of around 5%, some reports have associated antibiotic treatment with a worsening prognosis.

Case Presentation
We describe a female infant patient, initially treated for suspected meningococcal septicaemia, who went on to develop renal complications and thrombocytopenia characteristic of HUS. A subsequent positive stool sample for E. coli O157 confirmed HUS as an appropriate diagnosis, although there was no evidence of diarrhoea or vomiting throughout the course of her management.

Conclusion
The urgency of early recognition and treatment for suspected meningococcal disease in very young children while entirely appropriate can initially divert attention from other serious conditions. Evidence of infection with E. coli O157 infection in this case also highlights what can be a blurred distinction between atypical (non-diarrhoeal) HUS from classical HUS of infective origin.
Analysis of C4 and the C4 binding protein in the MRL/lpr mouse
Authors: Wenderfer Scott E , Soimo Kipruto , Wetsel Rick A , Braun Michael C 
Published: October 2007

AbstractSystemic lupus erythematosus is a complement-mediated autoimmune disease. While genetic deficiencies of classical pathway components lead to an increased risk of developing systemic lupus erythematosus, end organ damage is associated with complement activation and immune complex deposition. The role of classical pathway regulators in systemic lupus erythematosus is unknown. C4 binding protein (C4bp) is a major negative regulator of the classical pathway. In order to study the role of C4bp deficiency in an established murine model of lupus nephritis, mice with a targeted deletion in the gene encoding C4bp were backcrossed into the MRL/lpr genetic background. Compared with control MRL/lpr mice, C4bp knockout MLR/lpr mice had similar mortality and similar degrees of lymphoproliferation. There were no differences in the extent of proteinuria or renal inflammation. Staining for complement proteins and immunoglobulins in the kidneys of diseased mice revealed no significant strain differences. Moreover, there was no difference in autoantibody production or in levels of circulating immune complexes. In comparison with C57BL/6 mice, MRL/lpr mice had depressed C4 levels as early as 3 weeks of age. The absence of C4bp did not impact serum C4 levels or alter classical pathway hemolytic activity. Given that immune complex renal injury in the MRL/lpr mouse is independent of Fc receptors as well as the major negative regulator of the classical pathway, new mechanisms for immune-complex-mediated renal injury need to be considered.
Cellular turnover and expression of hypoxic-inducible factor in acute acalculous and calculous cholecystitis
Authors: Vakkala Merja , Laurila Jouko J , Saarnio Juha , Koivukangas Vesa , Syrjälä Hannu , Karttunen Tuomo , Soini Ylermi , Ala-Kokko Tero I 
Published: October 2007

Abstract
Introduction
Epithelial corrective and destructive mechanisms have not been studied in inflammatory gallbladder disease.

Methods
Epithelial apoptosis, cell proliferation and expression of hypoxia-inducible factor (HIF)-1α were compared in gallbladders from patients with acute acalculous cholecystitis (AAC; n = 30) and acute calculous cholecystitis (ACC; n = 21), and from patients undergoing surgery for other reasons (normal gallbladders; n = 9), which were removed during open cholecystectomy. The immunohistochemical stains included antibodies to Ki-67 (proliferation), M30 (apoptosis) and HIF-1α. Proliferation and apoptosis were expressed as percentages of positive cells. HIF-1α expression was expressed as absent, weak, or strong.

Results
Apoptosis (median [25th to 75th percentile]) was significantly increased in AAC (1.31% [0.75% to 1.8%], P < 0.001) and ACC (1.10% [0.63% to 1.64%], P = 0.001), compared with control samples (0.20% [0.07% to 0.45%]. The proliferation rate was significantly increased in AAC (8.0% [4.0% to 17.0%], P < 0.001) and ACC (14% [7.5% to 26.5%], P = 0.001) compared with control samples (1.0% [1.0% to 3.0%]). Strong HIF-1α staining was observed in 57% of AAC, in 100% of ACC and in 44% of control specimens (P < 0.001). Intense HIF-1α expression was associated with increased cell proliferation (P = 0.002).

Conclusion
Cell proliferation and apoptosis were increased in AAC and ACC, as compared with normal gallbladders. Expression of HIF-1α was lower in AAC than in ACC.
Cortisol and post-traumatic stress disorder in adults
Authors: Meewisse Marie-Louise , Reitsma Johannes B. , De Vries Giel-Jan , Gersons Berthold P. R. , Olff Miranda 
Published: October 2007

BackgroundPost-traumatic stress disorder (PTSD) has inconsistently been associated with lower levels of cortisol.AimsTo compare basal cortisol levels in adults with current PTSD and in people without psychiatric disorder.MethodSystematic review and meta-analysis. Standardised mean differences (SMD) in basal cortisol levels were calculated and random-effects models using inverse variance weighting were applied.ResultsAcross 37 studies, 828 people with PTSD and 800 controls did not differ in cortisol levels (pooled SMD = −0.12, 95% C1= −0.32 to 0.080). Subgroup analyses revealed that studies assessing plasma or serum showed significantly lower levels in people with PTSD than in controls not exposed to trauma. Lower levels were also found in people with PTSD when females were included, in studies on physical or sexual abuse, and in afternoon samples.ConclusionsLow cortisol levels in PTSD are only found under certain conditions. Future research should elucidate whether low cortisol is related to gender or abuse and depends on the measurement methods used.
Effects of treating postnatal depression on mother-infant interaction and child development
Authors: Poobalan Amudha S. , Aucott Lorna S. , Ross Louise , Smith W. Cairns. S. , Helms Peter J. , Williams Justin H. G. 
Published: October 2007

BackgroundPostnatal depression has detrimental effects on the child's cognitive and emotional development.AimsTo assess the benefits of treating postnatal depression for mother–infant interaction and child development.MethodA systematic search was made of 12 electronic bibliographic databases for randomised controlled trials and controlled clinical trials on treatment of mothers with postnatal depression, where outcomes were assessed in children; findings were assessed.ResultsOnly eighttrials met the inclusion criteria. Of those included, interventions varied widely but all involved therapies directed at the mother–infant relationship. One study with intensive and prolonged therapy showed cognitive improvement, whereas two others with briefer interventions improved maternal–infant relationships but did not affect the child's cognitive or behavioural development. All five studies assessing only mother–infant relationships showed improvements.ConclusionsCognitive development in children of depressed mothers, along with better mother–infant relationships, might be improved with sustained interventions. Trials assessing treatments for postnatal depression would benefit from looking more closely at benefits for children as well as mothers, using validated objective measures.
Structured patient–clinician communication and 1-year outcome in community mental healthcare
Authors: Priebe Stefan , McCabe Rosemarie , Bullenkamp Jens , Hansson Lars , Lauber Christoph , Martinez-Leal Rafael , Rössler Wulf , Salize Hans , Svensson Bengt , Torres-Gonzales Francisco , Van Den Brink Rob , Wiersma Durk , Wright Donna J. 
Published: October 2007

BackgroundPatient–clinician communication is central to mental healthcare but neglected in research.AimsTo test a new computer-mediated intervention structuring patient–clinician dialogue (DIALOG) focusing on patients' quality of life and needs for care.MethodIn a cluster randomised controlled trial, 134 keyworkers in six countries were allocated to DIALOG or treatment as usual; 507 people with schizophrenia or related disorders were included. Every 2 months for 1 year, clinicians asked patients to rate satisfaction with quality of life and treatment, and request additional or different support. Responses were fed back immediately in screen displays, compared with previous ratings and discussed. Primary outcome was subjective quality of life, and secondary outcomes were unmet needs and treatment satisfaction.ResultsOf 507 patients, 56 were lost to follow-up and 451 were included in intention-to-treat analyses. Patients receiving the DIALOG intervention had better subjective quality of life, fewer unmet needs and higher treatment satisfaction after 12 months.ConclusionsStructuring patient–clinician dialogue to focus on patients' views positively influenced quality of life, needs for care and treatment satisfaction.
Overall Survival and Cause-Specific Mortality of Patients With Stage T1a,bN0M0 Breast Carcinoma
Authors: Hanrahan Emer O. , Gonzalez-Angulo Ana M. , Giordano Sharon H. , Rouzier Roman , Broglio Kristine R. , Hortobagyi Gabriel N. , Valero Vicente 
Published: October 2007

Purpose With mammographic screening, the frequency of diagnosis of stage T1a,bN0M0 breast cancer has increased. Prognosis after locoregional therapy and benefit from adjuvant systemic therapy are poorly defined. We reviewed T1a,bN0M0 breast cancer cases registered in the Surveillance, Epidemiology, and End Results (SEER) Program to investigate the impact of prognostic factors on breast cancer–specific (BCSM) and non–breast cancer–related mortality. Methods We identified T1a,bN0M0 breast cancer cases registered in the SEER Program from 1988 to 2001, and used the Kaplan-Meier product limit method to describe overall survival (OS). We estimated the probabilities of death resulting from breast cancer and from other causes, and analyzed associations of patient and tumor characteristics with OS, BCSM, and non–breast cancer–related mortality using the log-rank test, Cox proportional hazards models, and a competing-risk model. We constructed nomograms to assist physicians in adjuvant therapy decision making. Results We identified 51,246 T1a,bN0M0 cases. Median follow-up was 64 months (range, 1 to 167 months). Median age at diagnosis was 65 years (range, 20 to 101 years). Ten-year probabilities of all-cause mortality and BCSM were 24% and 4%, respectively. Characteristics associated with increased probability of BCSM included age younger than 50 years at diagnosis, high tumor grade, estrogen receptor–negative status, progesterone receptor–negative status, and fewer than six nodes removed at axillary dissection. The constructed nomograms allow a comparison of predicted breast cancer–specific survival and non-breast cancer–specific survival in individual patients. Conclusion Overall, the prognosis of patients with T1a,bN0M0 breast cancer is excellent. However, subgroups of patients who are at higher risk of BCSM and who should be considered for adjuvant systemic therapy can be identified.
Phase III, Double-Blind, Controlled Trial of Atamestane Plus Toremifene Compared With Letrozole in Postmenopausal Women With Advanced Receptor-Positive Breast Cancer
Authors: Goss Paul , Bondarenko Igor N. , Manikhas Georgiy N. , Pendergrass Kelly B. , Miller Wilson H. , Langecker Peter , Blanchett Dennis 
Published: October 2007

Purpose To compare time to progression (TTP) with a steroidal aromatase inhibitor (AI) atamestane (ATA) combined with toremifene (TOR; complete estrogen blockade) versus letrozole (LET) in receptor-positive advanced breast cancer (ABC). Patients and Methods Eligibility included postmenopausal receptor-positive ABC and adjuvant hormonal therapy completed more than 12 months prior to study entry. Participants received daily ATA 500 mg with TOR 60 mg (ATA + TOR), or letrozole 2.5 mg (LET). The primary end point was TTP, whereas secondary objectives included objective response (OR), overall survival (OS), and time to treatment failure (TTF). The study had 80% power to detect a 25% increase in TTP assuming a TTP of 9.4 months in the LET population. Results A total of 865 patients were randomly assigned (434 to ATA + TOR and 431 to LET) in 60 centers in the United States, Canada, Russia, and Ukraine. Baseline characteristics were balanced. Median TTP was identical in the two arms at 11.2 months (P < .92). Median TTF was similar at 9.24 months (ATA + TOR) versus 10.44 months (LET). The hazard ratios (LET/ATA + TOR) were 1.00 (95% CI, 0.92 to 1.08) for TTP, 0.99 (95% CI, 0.92 to 1.06) for TTF, and 0.98 (95% CI, 0.87 to 1.11) for OS. OR occurred in 30% of patients receiving ATA + TOR and in 36% of patients receiving LET (P < .1). Adverse events (AEs) were similar for patients receiving ATA + TOR versus LET, and serious AEs were 10% v 11%, respectively. Conclusion TTP for patients receiving ATA + TOR was identical to that for patients receiving LET, representing the first endocrine therapy comparable to LET in ABC. Unlike in the Anastrozole, Tamoxifen, and Combined trial, addition of an antiestrogen did not decrease efficacy of the AI. Future studies of AIs in combination with more effective selective estrogen receptor modulators or selective receptor downregulators is warranted.
Epigenetic Silencing of Cyclooxygenase-2 Affects Clinical Outcome in Gastric Cancer
Authors: de Maat Michiel F.G. , van de Velde Cornelis J.H. , Umetani Naoyuki , de Heer Pieter , Putter Hein , van Hoesel Anneke Q. , Meijer Gerrit A. , van Grieken Nicole C. , Kuppen Peter J.K. , Bilchik Anton J. , Tollenaar Rob A.E.M. , Hoon Dave S.B. 
Published: October 2007

Purpose Overexpression of cyclooxygenase-2 (COX-2) in gastric cancer has been shown to enhance tumor progression. We investigated whether silencing by promoter region hypermethylation of the COX-2 gene contributes to disease outcome in gastric cancer. Materials and Methods COX-2 methylation status was initially assessed by capillary array electrophoresis methylation–specific polymerase chain reaction (CAE-MSP) and COX-2 protein expression by immunohistochemistry (IHC) in 40 primary gastric cancer tissues in a pilot study. Prognostic end points of correlative studies of COX-2 methylation status were time to recurrence, overall survival, and standard clinicopathologic features. CAE-MSP analysis was then validated in a second independent gastric cancer population (n = 137). Results COX-2 methylation was detected in 23% and 28% of the pilot and validation patient groups, respectively. COX-2 expression (IHC) in gastric tumors inversely correlated with COX-2 gene methylation status in the pilot study (P = .02). COX-2 methylation in tumors was significantly associated with lower T, N, and TNM stage in the validation patient group (P = .02, P = .006, and P = .008, respectively). Patients with COX-2 methylated tumors had significantly longer time to recurrence and improved overall survival in a multivariate analysis in the validation patient group (hazard ratio[HR], 0.49; 95% CI, 0.24% to 0.99%; HR, 0.62; 95% CI, 0.38% to 0.99%, respectively). Conclusion Hypermethylation of COX-2 gene promoter was identified as an independent prognostic factor in gastric cancer patients. The results suggest promoter hypermethylation to be an important regulatory mechanism of COX-2 expression in gastric cancer and an important prognostic biomarker.
CNS or Bone Marrow Involvement As Risk Factors for Poor Survival in Post-Transplantation Lymphoproliferative Disorders in Children After Solid Organ Transplantation
Authors: Maecker Britta , Jack Thomas , Zimmermann Martin , Abdul-Khaliq Hashim , Burdelski Martin , Fuchs Alexandra , Hoyer Peter , Koepf Sabine , Kraemer Ulrike , Laube Guido F. , Müller-Wiefel Dirk E. , Netz Heinrich , Pohl Martin , Toenshoff Burkhard , Wagner Hans-Joachim , Wallot Michael , Welte Karl , Melter Michael , Offner Gisela , Klein Christoph 
Published: October 2007

Purpose To identify prognostic factors of survival in pediatric post-transplantation lymphoproliferative disorder (PTLD) after solid organ transplantation. Patients and Methods A multicenter, retrospective case analysis of 55 pediatric solid organ graft recipients (kidney, liver, heart/lung) developing PTLD were reported to the German Pediatric-PTLD registry. Patient charts were analyzed for tumor characteristics (histology, immunophenotypes, cytogenetics, Epstein-Barr virus [EBV] detection), stage, treatment, and outcome. Probability of overall and event-free survival was analyzed in defined subgroups using univariate and Cox regression analyses. Results PTLD was diagnosed at a median time of 29 months after organ transplantation, with a significantly shorter lag time in liver (0.83 years) versus heart or renal graft recipients (3.33 and 3.10 years, respectively; P = .001). The 5-year overall and event-free survival was 68% and 59%, respectively, with 59% of patients surviving 10 years. Stage IV disease with bone marrow and/or CNS involvement was associated independently with poor survival (P = .0005). No differences in outcome were observed between early- and late-onset PTLD, monomorphic or polymorphic PTLD, and EBV-positive or EBV-negative PTLD, respectively. Patients with Burkitt or Burkitt-like PTLD and c-myc translocations had short survival (< 1 year). Conclusion Stage IV disease is an independent risk factor for poor survival in pediatric PTLD patients. Prospective multicenter trials are needed to delineate additional risk factors and to assess treatment approaches for pediatric PTLD.
Assessment of Response to Induction Therapy and Its Influence on 5-Year Failure-Free Survival in Group III Rhabdomyosarcoma: The Intergroup Rhabdomyosarcoma Study-IV Experience—A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group
Authors: Burke Megan , Anderson James R. , Kao Simon C. , Rodeberg David , Qualman Stephen J. , Wolden Suzanne L. , Meyer William H. , Breitfeld Philip P. 
Published: October 2007

Purpose Initial response to induction chemotherapy predicts failure-free survival (FFS) in osteosarcoma and Ewing's sarcoma. For Intergroup Rhabdomyosarcoma Study (IRS) IV patients with group III rhabdomyosarcoma, we assessed whether reported response assessed by anatomic imaging at week 8 predicted FFS. Patients and Methods We studied 444 group III patients who received induction therapy, had response assessed at week 8 by anatomic imaging, and continued with protocol therapy. Induction chemotherapy was generally followed by radiation therapy (RT) starting after week 9. Response to induction therapy was determined at weeks 0 and 8. Local institutions coded response. Results Response rate for the entire cohort at week 8 was 77% (95% CI, 73% to 81%; complete response [CR], 21%; partial response [PR], 56%) but response had no influence on FFS (P = .57). Two hundred seventy-two patients received standard-timing RT at week 9 and thus only chemotherapy during induction. Response rate was 81% (95% CI, 76% to 86%; CR, 22%; PR, 59%). In these patients, response did not influence FFS except for those with alveolar histology. One hundred thirty-two other patients received chemotherapy and RT during induction (up-front RT). Response rate was 65% (95% CI, 57% to 73%; CR, 12%; PR, 53%), but response had no influence on FFS (P = .69). Forty patients received no RT at all (protocol violation) and response to induction therapy had no effect on FFS. Conclusion In IRS-IV, response rate to induction therapy was 77% in group III patients, was independent of histology, and had no influence on FFS overall.