bluuebunny/crossref_metadata_2025_split huggingface dataset:
Argatroban administration reduces leukocyte adhesion and improves capillary perfusion within the intestinal microcirculation in experimental sepsis
Authors: Fuchs Christian , Ladwig Elena , Zhou Juan , Pavlovic Dragan , Behrend Kristina , Whynot Sara , Hung Orlando , Murphy Michael , Cerny Vladimir , Lehmann Christian 
Published: August 2010

SummaryCo-activation of pro-coagulatory pathways in sepsis may result in disseminated intravascular coagulation and contributes to microvascular dysfunction. We investigated the effects of the direct thrombin inhibitor, argatroban (ARG), on the sepsis-induced impairment of the intestinal microcirculation (capillary perfusion, leukocyte adhesion) and the vascular contractility in rats. Forty male Lewis rats were randomly assigned to one of four groups: sham surgery (SHAM), experimental sepsis (colon ascendens stent peritonitis – CASP), CASP+ARG, and SHAM+ARG. At 16 hours after colon stent insertion (or sham surgery), 2 mg/kg argatroban or buffer were given intravenously, and 1 hour thereafter, intravital microscopy was performed. In addition, experiments to study the impact of ARG on vascular contractility were conducted in vitro. ARG administration in CASP rats significantly increased functional capillary density in mucosal (+128%) and muscular layers (longitudinal: +42%; circular: +64%) and decreased the number of firmly adhering leukocytes in the intestinal submucosa compared to untreated animals. In vitro findings indicated a vasodilating effect of ARG. ARG administration during experimental sepsis improved intestinal microcirculation by preserving functional capillary density, an indicator of microvascular perfusion, and by reducing leukocyte adherence to the endothelium in submucosal venules.
Spatial Perspective and Coordinate Systems in Autoscopy: A Case Report of a “Fantome de Profil” in Occipital Brain Damage
Authors: Bolognini Nadia , Làdavas Elisabetta , Farnè Alessandro 
Published: August 2010

Abstract
Autoscopic phenomena refer to complex experiences involving the illusory reduplication of one's own body. Here we report the third long-lasting case of autoscopy in a patient with right occipital lesion. Instead of the commonly reported frontal mirror view (fantôme spéculaire), the patient saw her head and upper trunk laterally in side view (fantôme de profil). We found that the visual appearance and completeness of the autoscopic image could be selectively modulated by active and passive movements, without being influenced by imagining the same movements or by tactile and auditory stimulation. Eyes closure did not disrupt either the perception of the autoscopic body or the effects of the motor stimulation. Moreover, the visual body reduplication was coded neither in purely eye-centered nor in head-centered frames of reference, suggesting the involvement of egocentric coordinate systems (eyes and head centered). A follow-up examination highlighted the stability of the visual characteristics of the body reduplication and its shift induced by displacement of both head and eyes. These findings support the view that autoscopic phenomena have a multisensory motor origin and proprioceptive signals may play an important role in modulating the illusory visual reduplication of the patient's own body, most likely via cross-modal modulation of extrastriate areas involved in body and face perception.
The GENERATE project: Curricular and pedagogical inspiration from parents and their children working together
Authors: Barnes Jonathan 
Published: August 2010

This report summarizes GENERATE, a pilot research project conducted by 12 artists and their children 3—14. Simply put, these artist/art educator/parents allowed their own children unlimited access to their studios, materials, equipment and workspaces for two years. During that time the children were able to work alongside their parents on making combined and separate art works and contribute to a series of public exhibitions. The project was sponsored by The Turner Contemporary in Margate and the University of the Creative Arts (UCA). The artist/parents kept logs or diaries of what happened, and attended a series of joint meetings to discuss developments. At the same time a series of public workshops were organized (sometimes from a large trailer parked in a shopping centre car park) in which other children and parents from Thanet, Kent were encouraged to spend time making art together. The researcher collected evidence of the progress of the project from observations, discussions, telephone and email communications, photographs and the logs of the artists involved. The report discusses the challenges this project has raised regarding: • definitions of creativity • adult artist’s conceptions of art • the motivations towards creativity • the teach-ability of creativity • parenting • inter-generational learning • child-led aspects of schooling.
A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma
Authors: Chauhan Dharminder , Singh Ajita V. , Aujay Monette , Kirk Christopher J. , Bandi Madhavi , Ciccarelli Bryan , Raje Noopur , Richardson Paul , Anderson Kenneth C. 
Published: August 2010

Abstract
Bortezomib therapy has proven successful for the treatment of relapsed, relapsed/refractory, and newly diagnosed multiple myeloma (MM). At present, bortezomib is available as an intravenous injection, and its prolonged treatment is associated with toxicity and development of drug resistance. Here we show that the novel proteasome inhibitor ONX 0912, a tripeptide epoxyketone, inhibits growth and induces apoptosis in MM cells resistant to conventional and bortezomib therapies. The anti-MM activity of ONX-0912 is associated with activation of caspase-8, caspase-9, caspase-3, and poly(ADP) ribose polymerase, as well as inhibition of migration of MM cells and angiogenesis. ONX 0912, like bortezomib, predominantly inhibits chymotrypsin-like activity of the proteasome and is distinct from bortezomib in its chemical structure. Importantly, ONX 0912 is orally bioactive. In animal tumor model studies, ONX 0912 significantly reduced tumor progression and prolonged survival. Immununostaining of MM tumors from ONX 0912–treated mice showed growth inhibition, apoptosis, and a decrease in associated angiogenesis. Finally, ONX 0912 enhances anti-MM activity of bortezomib, lenalidomide dexamethasone, or pan-histone deacetylase inhibitor. Taken together, our study provides the rationale for clinical protocols evaluating ONX 0912, either alone or in combination, to improve patient outcome in MM.
The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear
Authors: Paudyal Anju , Damrau Christine , Patterson Victoria L , Ermakov Alexander , Formstone Caroline , Lalanne Zuzanna , Wells Sara , Lu Xiaowei , Norris Dominic P , Dean Charlotte H , Henderson Deborah J , Murdoch Jennifer N 
Published: August 2010

Abstract

Background
The planar cell polarity (PCP) signalling pathway is fundamental to a number of key developmental events, including initiation of neural tube closure. Disruption of the PCP pathway causes the severe neural tube defect of craniorachischisis, in which almost the entire brain and spinal cord fails to close. Identification of mouse mutants with craniorachischisis has proven a powerful way of identifying molecules that are components or regulators of the PCP pathway. In addition, identification of an allelic series of mutants, including hypomorphs and neomorphs in addition to complete nulls, can provide novel genetic tools to help elucidate the function of the PCP proteins.

Results
We report the identification of a new N-ethyl-N-nitrosourea (ENU)-induced mutant with craniorachischisis, which we have named chuzhoi (chz). We demonstrate that chuzhoi mutant embryos fail to undergo initiation of neural tube closure, and have characteristics consistent with defective convergent extension. These characteristics include a broadened midline and reduced rate of increase of their length-to-width ratio. In addition, we demonstrate disruption in the orientation of outer hair cells in the inner ear, and defects in heart and lung development in chuzhoi mutants. We demonstrate a genetic interaction between chuzhoi mutants and both Vangl2

Lp
and Celsr1

Crsh
mutants, strengthening the hypothesis that chuzhoi is involved in regulating the PCP pathway. We demonstrate that chuzhoi maps to Chromosome 17 and carries a splice site mutation in Ptk7. This mutation results in the insertion of three amino acids into the Ptk7 protein and causes disruption of Ptk7 protein expression in chuzhoi mutants.

Conclusions
The chuzhoi mutant provides an additional genetic resource to help investigate the developmental basis of several congenital abnormalities including neural tube, heart and lung defects and their relationship to disruption of PCP. The chuzhoi mutation differentially affects the expression levels of the two Ptk7 protein isoforms and, while some Ptk7 protein can still be detected at the membrane, chuzhoi mutants demonstrate a significant reduction in membrane localization of Ptk7 protein. This mutant provides a useful tool to allow future studies aimed at understanding the molecular function of Ptk7.
Wallerian-like axonal degeneration in the optic nerve after excitotoxic retinal insult: an ultrastructural study
Authors: Saggu Sarabjit K , Chotaliya Hiren P , Blumbergs Peter C , Casson Robert J 
Published: August 2010

Abstract

Background
Excitotoxicity is involved in the pathogenesis of a number neurodegenerative diseases, and axonopathy is an early feature in several of these disorders. In models of excitotoxicity-associated neurological disease, an excitotoxin delivered to the central nervous system (CNS), could trigger neuronal death not only in the somatodendritic region, but also in the axonal region, via oligodendrocyte N-methyl-D-aspartate (NMDA) receptors. The retina and optic nerve, as approachable regions of the brain, provide a unique anatomical substrate to investigate the "downstream" effect of isolated excitotoxic perikaryal injury on central nervous system (CNS) axons, potentially providing information about the pathogenesis of the axonopathy in clinical neurological disorders.
Herein, we provide ultrastructural information about the retinal ganglion cell (RGC) somata and their axons, both unmyelinated and myelinated, after NMDA-induced retinal injury. Male Sprague-Dawley rats were killed at 0 h, 24 h, 72 h and 7 days after injecting 20 nM NMDA into the vitreous chamber of the left eye (n = 8 in each group). Saline-injected right eyes served as controls. After perfusion fixation, dissection, resin-embedding and staining, ultrathin sections of eyes and proximal (intraorbital) and distal (intracranial) optic nerve segments were evaluated by transmission electron tomography (TEM).

Results
TEM demonstrated features of necrosis in RGCs: mitochondrial and endoplasmic reticulum swelling, disintegration of polyribosomes, rupture of membranous organelle and formation of myelin bodies. Ultrastructural damage in the optic nerve mimicked the changes of Wallerian degeneration; early nodal/paranodal disturbances were followed by the appearance of three major morphological variants: dark degeneration, watery degeneration and demyelination.

Conclusion
NMDA-induced excitotoxic retinal injury causes mainly necrotic RGC somal death with Wallerian-like degeneration of the optic nerve. Since axonal degeneration associated with perikaryal excitotoxic injury is an active, regulated process, it may be amenable to therapeutic intervention.
Metabolic syndrome predicts vascular changes in whole body magnetic resonance imaging in patients with long standing diabetes mellitus
Authors: Findeisen Hannes M , Weckbach Sabine , Stark Renée G , Reiser Maximilian F , Schoenberg Stefan O , Parhofer Klaus G 
Published: August 2010

Abstract

Background
Although diabetic patients have an increased rate of cardio-vascular events, there is considerable heterogeneity with respect to cardiovascular risk, requiring new approaches to individual cardiovascular risk factor assessment. In this study we used whole body-MR-angiography (WB-MRA) to assess the degree of atherosclerosis in patients with long-standing diabetes and to determine the association between metabolic syndrome (MetS) and atherosclerotic burden.

Methods
Long standing (≥10 years) type 1 and type 2 diabetic patients (n = 59; 31 males; 63.3 ± 1.7 years) were examined by WB-MRA. Based on the findings in each vessel, we developed an overall score representing the patient's vascular atherosclerotic burden (MRI-score). The score's association with components of the MetS was assessed.

Results
The median MRI-score was 1.18 [range: 1.00-2.41] and MetS was present in 58% of the cohort (type 2 diabetics: 73%; type 1 diabetics: 26%). Age (p = 0.0002), HDL-cholesterol (p = 0.016), hypertension (p = 0.0008), nephropathy (p = 0.0093), CHD (p = 0.001) and MetS (p = 0.0011) were significantly associated with the score. Adjusted for age and sex, the score was significantly (p = 0.02) higher in diabetics with MetS (1.450 [1.328-1.572]) compared to those without MetS (1.108 [0.966-1.50]). The number of MetS components was associated with a linear increase in the MRI-score (increase in score: 0.09/MetS component; r2 = 0.24, p = 0.038). Finally, using an established risk algorithm, we found a significant association between MRI-score and 10-year risk for CHD, fatal CHD and stroke.

Conclusion
In this high-risk diabetic population, WB-MRA revealed large heterogeneity in the degree of systemic atherosclerosis. Presence and number of traits of the MetS are associated with the extent of atherosclerotic burden. These results support the perspective that diabetic patients are a heterogeneous population with increased but varying prevalence of atherosclerosis and risk.
The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins
Authors: Cornock Ruth , Langley-Evans Simon C , Mobasheri Ali , McMullen Sarah 
Published: August 2010

Abstract

Background
Maternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma volume expansion. The study focused on expression of renal angiotensin receptors (ATR) and vasopressin-related aquaporins (AQP), hypothesising that an alteration in the balance of these proteins would be associated with pregnancy per se and with compromised plasma volume expansion in rats fed a low-protein diet.

Methods
Female Wistar rats were mated and fed a control (18% casein) or low-protein (9% casein) diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point) for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle.

Results
As expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT2R protein expression was observed in low-protein fed animals alongside a decrease in creatinine clearance.

Conclusion
Regulatory systems involved in the pregnancy-induced plasma volume expansion are susceptible to the effects of maternal protein restriction.
Dynamic analysis of CD127 expression on memory CD8 T cells from patients with chronic hepatitis B during telbivudine treatment
Authors: Lv Guocai , Ying Linjung , Ma Wen-Jiang , Jin Xi , Zheng Lin , Li Lanjuan , Yang Yida 
Published: August 2010

Abstract

Background
Accumulating evidence supports the theory that expression of CD127 on CD8 T cells during the process of antiviral immune response indicates a subset of effect CD8 T cells that successfully develop into fully protective memory. CD8 T cells expression of CD127 may be used as a predictor to evaluate disease status in chronic viral infection. The aim of this study was to investigate the CD127 expression level on different subsets of CD8 T cell and explore the relationship between CD127 expression on CD8 memory T cells and serum hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) levels in patients with chronic hepatitis B (CHB). We also aimed to investigate the CD127 expression pattern on CD8 memory T cells of CHB patients who were treated with Telbivudine.

Methods/Results
Twenty HBeAg-positive CHB patients were selected and treated with telbivudine 600 mg/day for 48 weeks. The memory CD8 T cells were characterized by expression of CD45RA and CD27 markers. CD127 expression on the CD8 T-cell surface was measured by four-colour flow cytometry. Our results showed that CD127 expression on memory CD8 T cells was reduced in CHB patients. There was a strong negative correlation between CD127 expression on memory CD8 T cells and serum HBV DNA and HBeAg levels in CHB patients. Moreover, successful antiviral therapy increased CD127 expression on CD8 memory T cells as well as on HBV-specific CD8 T cells in CHB patients.

Conclusion
These results suggest that diminished CD127 expression on CD8 memory T cells of CHB patients is a potential mechanism explaining cellular immune function impairment in CHB infection, and that CD127 expression on CD8 memory T cells is a useful indicator for evaluating the effects of anti-HBV therapy.
Ectopic corticotropin-releasing hormone (CRH) syndrome from metastatic small cell carcinoma: a case report and review of the literature
Authors: Shahani Sadeka , Nudelman Rodolfo J , Nalini Ramaswami , Kim Han-Seob , Samson Susan L 
Published: August 2010

Abstract

Background
Cushing's Syndrome (CS) which is caused by isolated Corticotropin-releasing hormone (CRH) production, rather than adrenocorticotropin (ACTH) production, is extremely rare.

Methods
We describe the clinical presentation, course, laboratory values and pathologic findings of a patient with isolated ectopic CRH causing CS. We review the literature of the types of tumors associated with this unusual syndrome and the behavior of these tumors by endocrine testing.

Results
A 56 year old woman presented with clinical and laboratory features consistent with ACTH-dependent CS. Pituitary imaging was normal and cortisol did not suppress with a high dose dexamethasone test, consistent with a diagnosis of ectopic ACTH. CT imaging did not reveal any discrete lung lesions but there were mediastinal and abdominal lymphadenopathy and multiple liver lesions suspicious for metastatic disease. Laboratory testing was positive for elevated serum carcinoembryonic antigen and the neuroendocrine marker chromogranin A. Serum markers of carcinoid, medullary thyroid carcinoma, and pheochromocytoma were in the normal range. Because the primary tumor could not be identified by imaging, biopsy of the presumed metastatic liver lesions was performed. Immunohistochemistry was consistent with a neuroendocrine tumor, specifically small cell carcinoma. Immunostaining for ACTH was negative but was strongly positive for CRH and laboratory testing revealed a plasma CRH of 10 pg/ml (normal 0 to 10 pg/ml) which should have been suppressed in the presence of high cortisol.

Conclusions
This case illustrates the importance of considering the ectopic production of CRH in the differential diagnosis for presentations of ACTH-dependent Cushing's Syndrome.
The role of adjuvant pelvic radiotherapy in rectal cancer with synchronous liver metastasis: a retrospective study
Authors: Kim Jun Won , Kim Yong Bae , Kim Nam-Kyu , Min Byung-Soh , Shin Sang Joon , Ahn Joong Bae , Koom Woong Sub , Seong Jinsil , Keum Ki Chang 
Published: August 2010

Abstract

Background
Synchronous liver metastases are detected in approximately 25% of colorectal cancer patients at diagnosis. The rates of local failure and distant metastasis are substantial in these patients, even after undergoing aggressive treatments including resection of primary and metastatic liver tumors. The purpose of this study was to determine whether adjuvant pelvic radiotherapy is beneficial for pelvic control and overall survival in rectal cancer patients with synchronous liver metastasis after primary tumor resection.

Methods
Among rectal cancer patients who received total mesorectal excision (TME) between 1997 and 2006 at Yonsei University Health System, eighty-nine patients diagnosed with synchronous liver metastasis were reviewed. Twenty-seven patients received adjuvant pelvic RT (group S + R), and sixty-two patients were managed without RT (group S). Thirty-six patients (58%) in group S and twenty patients (74%) in group S+R received local treatment for liver metastasis. Failure patterns and survival outcomes were analyzed.

Results
Pelvic failure was observed in twenty-five patients; twenty-one patients in group S (34%), and four patients in group S+R (15%) (p = 0.066). The two-year pelvic failure-free survival rates (PFFS) of group S and group S+R were 64.8% and 80.8% (p = 0.028), respectively, and the two-year overall survival rates (OS) were 49.1% and 70.4% (p = 0.116), respectively. In a subgroup analysis of fifty-six patients who received local treatment for liver metastasis, the two-year PFFS were 64.9% and 82.9% (p = 0.05), respectively; the two-year OS were 74.1% and 80.0% (p = 0.616) in group S (n = 36) and group S+R (n = 20), respectively.

Conclusions
Adjuvant pelvic RT significantly reduced the pelvic failure rate but its influence on overall survival was unclear. Rectal cancer patients with synchronous liver metastasis may benefit from adjuvant pelvic RT through an increased pelvic control rate and improved quality of life.