bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stiffness parameters, intima-media thickness and early atherosclerosis in systemic lupus erythematosus patients
Authors: Cacciapaglia F , Zardi EM , Coppolino G , Buzzulini F , Margiotta D , Arcarese L , Vadacca M , Amoroso A , Afeltra A 
Published: February 2009

Detection of early carotid vascular disease in patients with systemic lupus erythematosus (SLE) is considered mandatory for evaluation of subclinical atherosclerosis (ATS), and various ultrasonographic (US) parameters have been proposed. In the present investigation, 33 SLE and 33 healthy age-matched females have been studied by colour-coded sonography of the common carotid artery, assessing intima-media thickness (IMT), vascular strain (VS), vascular distensibility (VD), vascular stiffness (VSf) and pressure-strain elastic modulus (PSEM) as possible markers of early ATS. Patients with SLE, despite equivalent exposure to “traditional” cardiovascular risk factors, presented a higher mean IMT of the common carotid artery than healthy subjects (0.7 ± 0.2 mm vs 0.5 ± 0.1 mm – P < 0.0001). Of the stiffness parameters, patients with lupus showed a mean VSf of 0.72 ± 0.38 vs 0.54 ± 0.14 in controls ( P < 0.0001) and a mean PSEM of 6.0 ± 2.8 Pa vs 3.0 ± 1.4 Pa in controls ( P < 0.0001). Mean VS and VD were significantly lower in patients with SLE than in healthy subjects ( P < 0.0001). Among individuals with IMT < 0.6 mm, patients with SLE presented more compromised stiffness parameters. IMT was shown to be a useful parameter in the evaluation of vascular damage, even in a “sub-clinical” phase, while stiffness parameters provide additional details regarding endothelial and vessel functional state. Combined evaluation may allow ATS to be detected in the early stages in patients with SLE.
Anchoring of FLT3 in the endoplasmic reticulum alters signaling quality
Authors: Schmidt-Arras Dirk , Böhmer Sylvia-Annette , Koch Sina , Müller Jörg P. , Blei Lutz , Cornils Hauke , Bauer Reinhard , Korasikha Sridhar , Thiede Christian , Böhmer Frank-D. 
Published: February 2009

Abstract
The mechanism of cell transformation by Fms-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia (AML) is incompletely understood. The most prevalent activated mutant FLT3 ITD exhibits an altered signaling quality, including strong activation of the STAT5 transcription factor. FLT3 ITD has also been found partially retained as a high-mannose precursor in an intracellular compartment. To analyze the role of intracellular retention of FLT3 for transformation, we have generated FLT3 versions that are anchored in the perinuclear endoplasmic reticulum (ER) by appending an ER retention sequence containing a RRR (R3) motif. ER retention of R3, but not of corresponding A3 FLT3 versions, is shown by biochemical, fluorescence-activated cell sorting, and immunocytochemical analyses. ER anchoring reduced global autophosphorylation and diminished constitutive activation of ERK1/2 and AKT of the constitutively active FLT3 versions. ER anchoring was, however, associated with elevated signaling to STAT3. Transforming activity of the FLT3 D835Y mutant was suppressed by ER anchoring. In contrast, ER-anchored FLT3 ITD retained STAT5-activating capacity and was transforming in vitro and in vivo. The findings highlight another aspect of the different signaling quality of FLT3 ITD: It can transform cells from an intracellular location.
The molecular signature of CD8+ T cells undergoing deletional tolerance
Authors: Parish Ian A. , Rao Sudha , Smyth Gordon K. , Juelich Torsten , Denyer Gareth S. , Davey Gayle M. , Strasser Andreas , Heath William R. 
Published: February 2009

AbstractPeripheral tolerance induction is critical for the maintenance of self-tolerance and can be mediated by immunoregulatory T cells or by direct induction of T-cell anergy or deletion. Although the molecular processes underlying anergy have been extensively studied, little is known about the molecular basis for peripheral T-cell deletion. Here, we determined the gene expression signature of peripheral CD8+ T cells undergoing deletional tolerance, relative to those undergoing immunogenic priming or lymphopenia-induced proliferation. From these data, we report the first detailed molecular signature of cells undergoing deletion. Consistent with defective cytolysis, these cells exhibited deficiencies in granzyme up-regulation. Furthermore, they showed antigen-driven Bcl-2 down-regulation and early up-regulation of the proapoptotic protein Bim, consistent with the requirement of this BH3-only protein for peripheral T-cell deletion. Bim up-regulation was paralleled by defective interleukin-7 receptor α (IL-7Rα) chain reexpression, suggesting that Bim-dependent death may be triggered by loss of IL-7/IL-7R signaling. Finally, we observed parallels in molecular signatures between deletion and anergy, suggesting that these tolerance pathways may not be as molecularly distinct as previously surmised.
Comprehensive characterization of neuroblastoma cell line subtypes reveals bilineage potential similar to neural crest stem cells
Authors: Acosta Sandra , Lavarino Cinzia , Paris Raquel , Garcia Idoia , de Torres Carmen , Rodríguez Eva , Beleta Helena , Mora Jaume 
Published: February 2009

Abstract

Background
Neuroblastic tumors (NBT) derive from neural crest stem cells (NCSC). Histologically, NBT are composed by neuroblasts and Schwannian cells. In culture, neuroblastic (N-), substrate-adherent (S-) and intermediate phenotype (I-) cell subtypes arise spontaneously.

Methods
Here, neuroblastoma (NB) cell line subtypes were characterized according to embryonic peripheral nervous system development markers (GAP43, Phox2b, Sox10, c-kit, GD2, NF68, vimentin, S100β, calcyclin and ABCG2), morphological features, gene expression and differentiation potential. I-type cells were investigated as a bipotential (neuronal and glial) differentiation stage.

Results
Positive immunostaining of NCSC (GAP43, c-kit, NF68, vimentin and Phox2b) and undifferentiated cell (ABCG2) markers was observed in all NB subtypes. N- and I-type cells displayed cytoplasmic membrane GD2 staining, while nuclear calcyclin was restricted to S-type. N- and I-type cells showed similar phenotype and immunoreactivity pattern. Differential gene expression was associated with each cell subtype. N- and I-type cells displayed similar differentiation capacity towards neuronal and glial lineage fates. S-type cells, upon induction, did not show a neuronal-like phenotype, despite gene expression changes.

Conclusion
Results suggest that N- and I-type NB cell subtypes represent an immature bilineage stage, able to progress towards neuronal and glial fates upon induction of differentiation. S-type cells appear irreversibly committed to a glial lineage fate.
NF-κB activation by Helicobacter pylorirequires Akt-mediated phosphorylation of p65
Authors: Takeshima Eriko , Tomimori Koh , Kawakami Hirochika , Ishikawa Chie , Sawada Shigeki , Tomita Mariko , Senba Masachika , Kinjo Fukunori , Mimuro Hitomi , Sasakawa Chihiro , Fujita Jiro , Mori Naoki 
Published: February 2009

AbstractBackgroundThe inflammatory response inHelicobacter pylori-infected gastric tissue is mediated bycagpathogenicity island (PAI)-dependent activation of nuclear factor-κB (NF-κB). Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is known to play a role in NF-κB activation, but little information is available on the relationship betweenH. pyloriand PI3K/Akt signaling in gastric epithelial cells. We examined whetherH. pyloriactivates Akt in gastric epithelial cells, the role ofcagPAI in this process and the role of Akt in regulatingH. pylori-induced NF-κB activation.ResultsPhosphorylated Akt was detected in epithelial cells ofH. pylori-positive gastric tissues. Although Akt was activated in MKN45 and AGS cells by coculture withcagPAI-positiveH. pyloristrains, acagPAI-negative mutant showed no activation of Akt.H. pylorialso induced p65 phosphorylation. PI3K inhibitor suppressedH. pylori-induced p65 phosphorylation and NF-κB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominant-negative Akt inhibitedH. pylori-induced NF-κB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibitedH. pylori-induced interleukin-8 expression.ConclusionThe results suggest thatcagPAI-positiveH. pyloriactivates Akt in gastric epithelial cells and this may contribute toH. pylori-mediated NF-κB activation associated with mucosal inflammation and carcinogenesis.
A case-control study of sporadic Creutzfeldt-Jakob disease in Switzerland: analysis of potential risk factors with regard to an increased CJD incidence in the years 2001–2004
Authors: Ruegger Jessica , Stoeck Katharina , Amsler Lorenz , Blaettler Thomas , Zwahlen Marcel , Aguzzi Adriano , Glatzel Markus , Hess Klaus , Eckert Tobias 
Published: February 2009

Abstract

Background
In 2001, the observed annual mortality from Creutzfeldt-Jakob disease (CJD) in Switzerland increased from less than 1.5 to 2.6 per million inhabitants. An underlying cause could not be identified.

Methods
To analyse potential risk factors for sCJD in Switzerland, close relatives of 69 sCJD-patients and 224 frequency age-matched controls were interviewed in a case-control study using a standardised questionnaire. 135 potential risk factors including socio-demographics, medical history, occupation and diet were analysed by logistic regression adjusting for age, sex and education.

Results
sCJD patients were more likely to have travelled abroad, worked at an animal laboratory, undergone invasive dental treatment, orthopaedic surgery, ophthalmologic surgery after 1980, regular GP visits, taken medication regularly, and consumed kidney. No differences between patients and controls were found for residency, family history, and exposure to environmental and other dietary factors.

Conclusion
Although some factors were significantly more frequent among sCJD-cases, this study did not reveal specific explanations for the increased incidence of deaths due to sporadic CJD observed in Switzerland since 2001. Results have to be interpreted with caution due to multiple testing and possible recall bias in association with a long incubation period. The most plausible reason for the increase in Swiss sCJD cases after 2000 is an improved case ascertainment. Therefore, underreporting of cases might well have occurred before the year 2001, and the "real" yearly incidence of sCJD might not be lower than, but rather above 2 per million inhabitants.
Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
Authors: Glockzin Gabriel , Schlitt Hans J , Piso Pompiliu 
Published: February 2009

Abstract

Background
Peritoneal tumor dissemination arising from colorectal cancer, appendiceal cancer, gastric cancer, gynecologic malignancies or peritoneal mesothelioma is a common sign of advanced tumor stage or disease recurrence and mostly associated with poor prognosis.

Methods and results
In the present review article preoperative workup, surgical technique, postoperative morbidity and mortality rates, oncological outcome and quality of life after CRS and HIPEC are reported regarding the different tumor entities.

Conclusion
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide a promising combined treatment strategy for selected patients with peritoneal carcinomatosis that can improve patient survival and quality of life. The extent of intraperitoneal tumor dissemination and the completeness of cytoreduction are the leading predictors of postoperative patient outcome. Thus, consistent preoperative diagnostics and patient selection are crucial to obtain a complete macroscopic cytoreduction (CCR-0/1).
A new plasmid vector for DNA delivery using lactococci
Authors: Guimarães Valeria , Innocentin Sylvia , Chatel Jean-Marc , Lefèvre François , Langella Philippe , Azevedo Vasco , Miyoshi Anderson 
Published: February 2009

Abstract

Background
The use of food-grade lactococci as bacterial carriers to DNA delivery into epithelial cells is a new strategy to develop live oral DNA vaccine. Our goal was to develop a new plasmid, named pValac, for antigen delivery for use in lactococci. The pValac plasmid was constructed by the fusion of: i) a eukaryotic region, allowing the cloning of an antigen of interest under the control of the pCMV eukaryotic promoter to be expressed by a host cell and ii) a prokaryotic region allowing replication and selection of bacteria. In order to evaluate pValac functionality, the gfp ORF was cloned into pValac (pValac:gfp) and was analysed by transfection in PK15 cells. The applicability of pValac was demonstrated by invasiveness assays of Lactococcus lactis inlA+ strains harbouring pValac:gfp into Caco-2 cells.

Results
After transfection with pValac:gfp, we observed GFP expression in PK15 cells. L. lactis inlA+ were able to invade Caco-2 cells and delivered a functional expression cassette (pCMV:gfp) into epithelial cells.

Conclusion
We showed the potential of an invasive L. lactis harbouring pValac to DNA delivery and subsequent triggering DNA expression by epithelial cells. Further work will be to examine whether these strains are able to deliver DNA in intestinal cells in vivo.
Inducible mutant huntingtin expression in HN10 cells reproduces Huntington's disease-like neuronal dysfunction
Authors: Weiss Andreas , Roscic Ana , Paganetti Paolo 
Published: February 2009

AbstractBackgroundExpansion of a polyglutamine repeat at the amino-terminus of huntingtin is the probable cause for Huntington's disease, a lethal progressive autosomal-dominant neurodegenerative disorders characterized by impaired motor performance and severe brain atrophy. The expanded polyglutamine repeat changes the conformation of huntingtin and initiates a range of pathogenic mechanisms in neurons including intracellular huntingtin aggregates, transcriptional dysregulation, energy metabolism deficits, synaptic dystrophy and ultimately neurodegeneration. It is unclear how these events relate to each other or if they can be reversed by pharmacological intervention. Here, we describe neuronal cell lines expressing inducible fragments of normal and mutant huntingtin.ResultsIn HN10 cells, the expression of wild type and mutant huntingtin fragments was dependent on the induction time as well as on the concentration of the RheoSwitch®inducing ligand. In order to analyze the effect of mutant huntingtin expression on cellular functions we concentrated on the 72Q exon1 huntingtin expressing cell line and found that upon induction, it was possible to carefully dissect mutant huntingtin-induced phenotypes as they developed over time. Dysregulation of transcription as a result of mutant huntingtin expression showed a transcription signature replicating that reported in animal models and Huntington's disease patients. Crucially, triggering of neuronal differentiation in mutant huntingtin expressing cell resulted in the appearance of additional pathological hallmarks of Huntington's disease including cell death.ConclusionWe developed neuronal cell lines with inducible expression of wild type and mutant huntingtin. These new cell lines represent a reliablein vitrosystem for modeling Huntington's disease and should find wide use for high-throughput screening application and for investigating the biology of mutant huntingtin.
Pneumococcal sepsis presenting as acute compartment syndrome of the lower limbs: a case report
Authors: Doddi Sudeendra , Singhal Tarun , Sinha Prakash 
Published: February 2009

Abstract

Introduction
Acute compartment syndrome is a surgical emergency requiring immediate fasciotomy. Spontaneous onset of acute compartment syndrome of the lower limbs is rare. We present a very rare case of pneumococcal sepsis leading to spontaneous acute compartment syndrome.

Case presentation
A 40-year-old Caucasian man presented as an emergency with spontaneous onset of pain in both legs and signs of compartment syndrome. This was confirmed on fasciotomy. Blood culture grew Streptococcus pneumoniae.

Conclusion
Sepsis should be strongly suspected in bilateral acute compartment syndrome of spontaneous onset.
Relapsing massive metal bezoar: a case report
Authors: Prieto-Aldape Manuel Rodrigo , Almaguer-García Francisco Issac , Figueroa-Jiménez Sandra Edith , Fernández-Díaz Oscar , Mora-Huerta José Antonio , González-Ojeda Alejandro 
Published: February 2009

Abstract

Introduction
Bezoars are uncommon findings in the gastrointestinal tract and are composed of a wide variety of materials. We report a case of a relapsing metal bezoar in a man with schizophrenia.

Case presentation
A 34-year-old man presented with a history of sub-acute onset of mild diffuse abdominal pain and abdominal distention. Physical examination revealed dullness to percussion in the upper and lower left quadrants. Past medical history was remarkable for epilepsy, schizophrenia and previous abdominal surgery for intestinal occlusion. Plain radiographs revealed objects of metal density contained within a dilated stomach. Celiotomy was performed revealing more than 350 metal objects inside the stomach. The patient was discharged and referred to a psychiatric facility.

Conclusion
Intestinal occlusion in patients with psychiatric disorders can result from rare causes such as bezoars. This report alerts surgeons to rule out bezoars in the differential diagnosis of intestinal occlusion in people with mental health problems.
Experimental obstructive cholestasis: the wound-like inflammatory liver response
Authors: Aller María-Angeles , Arias Jorge-Luis , García-Domínguez Jose , Arias Jose-Ignacio , Durán Manuel , Arias Jaime 
Published: February 2009

AbstractObstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them.Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis.It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process – although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration.
Forgotten indwelling stent in a transplanted kidney: a case report
Authors: Bhuva Shaheel , Kennish Steven J , Wah Tze M 
Published: February 2009

Abstract

• Introduction
Forgotten or retained ureteric stents are a well-recognised phenomenon with the potential to cause a range of complications, the most dangerous of which is obstructive nephropathy. These risks are potentially devastating when the patient has a single functioning transplanted kidney. Here we describe the case of a renal transplantation patient with a forgotten ureteric stent of 10 years, who presented with irritative bladder symptoms and was successfully managed using a multimodal urological approach with specialist advice on antibiotic prophylaxis. To the best of our knowledge this is the longest documented time period for a forgotten ureteric stent in a transplantation patient and is unusual in that obstructive nephropathy did not occur.

• Case presentation
A 32-year-old man with a history of end stage renal failure of unknown aetiology received a cadaveric renal transplant in 1995. An indwelling JJ stent was placed at the time of transplant to protect the vesicoureteric anastomosis. The patient made an unremarkable recovery and initially attended regular follow up in the renal transplant clinic. He was subsequently lost to transplant clinic follow up. In 2005 at the age of 42 he was referred to a nephrologist with irritative bladder symptoms. Renal tract imaging with ultrasound and a plain film demonstrated a retained encrusted ureteric stent.

• Conclusion
The removal of a retained encrusted ureteric stent always provides a urological challenge. This case demonstrates that multimodal treatment involving a combination of endourological and percutaneous techniques can be employed with success even when the patient has a heavily encrusted stent for a single functioning transplanted kidney. Involvement of a microbiologist to advise on prophylactic antibiotics is deemed especially useful, as the immunosuppressed transplant patient is at particular risk of sepsis secondary to bacteraemia as a result of the endoscopic manipulation of the colonised encrusted stent. This case also provides further evidence to highlight the potential benefits of a stent registry.
Transcriptional induction of junctional adhesion molecule-C gene expression in activated T cells
Authors: Immenschuh Stephan , Naidu Srivatsava , Chavakis Triantafyllos , Beschmann Heike , Ludwig Ralf J , Santoso Sentot 
Published: February 2009

AbstractJunctional adhesion molecule (JAM)-C is an Ig superfamily protein, which is involved in the regulation of various inflammatory and vascular events such as transendothelial leukocyte migration. JAM-C is expressed highly on the surface of endothelial cells and platelets, whereas expression in T lymphocytes is not well studied. To investigate the specific gene regulation of JAM-C in T lymphocytes, we determined JAM-C expression in quiescent and activated human T cells. Treatment with the polyclonal T cell activator PHA increased surface and total JAM-C expression in T cells time- and dose-dependently, as determined by flow cytometry and immunoblot analysis. In contrast, no up-regulation of JAM-A in activated T cells was detectable. The highest level of JAM-C up-regulation by PHA was observed in CD3+forkhead box P3+ and CD4+CD25high T cells. Moreover, TCR activation with combined anti-CD3 and anti-CD28 stimulation induced JAM-C expression in T cells. JAM-C induction occurred at the mRNA level, suggesting a transcriptional regulatory mechanism of JAM-C expression. Accordingly, we studied the regulation of the human JAM-C gene promoter in transiently transfected T cells. Luciferase activity of a JAM-C promoter gene construct with three potential consensus sites for the transcription factor NFAT was induced markedly in activated T cells. Finally, pretreatment with two pharmacological inhibitors of calcineurin, cyclosporin A, and FK-506, but not with MAPK inhibitors, blocked JAM-C induction in activated T cells. In summary, JAM-C is up-regulated in activated human T lymphocytes via a transcriptional mechanism, suggesting a potential role of JAM-C in T cell functions.