bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal profile of body temperature in acute ischemic stroke: relation to stroke severity and outcome
Authors: Karaszewski Bartosz , Thomas Ralph GR , Dennis Martin S , Wardlaw Joanna M 
Published: October 2012

Abstract

Background
Pyrexia after stroke (temperature ≥37.5°C) is associated with poor prognosis, but information on timing of body temperature changes and relationship to stroke severity and subtypes varies.

Methods
We recruited patients with acute ischemic stroke, measured stroke severity, stroke subtype and recorded four-hourly tympanic (body) temperature readings from admission to 120 hours after stroke. We sought causes of pyrexia and measured functional outcome at 90 days. We systematically summarised all relevant previous studies.

Results
Amongst 44 patients (21 males, mean age 72 years SD 11) with median National Institute of Health Stroke Score (NIHSS) 7 (range 0–28), 14 had total anterior circulation strokes (TACS). On admission all patients, both TACS and non-TACS, were normothermic (median 36.3°C vs 36.5°C, p=0.382 respectively) at median 4 hours (interquartile range, IQR, 2–8) after stroke; admission temperature and NIHSS were not associated (r2=0.0, p=0.353). Peak temperature, occurring at 35.5 (IQR 19.0 to 53.8) hours after stroke, was higher in TACS (37.7°C) than non-TACS (37.1°C, p<0.001) and was associated with admission NIHSS (r2=0.20, p=0.002). Poor outcome (modified Rankin Scale ≥3) at 90 days was associated with higher admission (36.6°C vs. 36.2°C p=0.031) and peak (37.4°C vs. 37.0°C, p=0.016) temperatures. Sixteen (36%) patients became pyrexial, in seven (44%) of whom we found no cause other than the stroke.

Conclusions
Normothermia is usual within the first 4 hours of stroke. Peak temperature occurs at 1.5 to 2 days after stroke, and is related to stroke severity/subtype and more closely associated with poor outcome than admission temperature. Temperature-outcome associations after stroke are complex, but normothermia on admission should not preclude randomisation of patients into trials of therapeutic hypothermia.
Colloid cyst of the third ventricle, hypothalamus, and heart: a dangerous link for sudden death
Authors: Turillazzi Emanuela , Bello Stefania , Neri Margherita , Riezzo Irene , Fineschi Vittorio 
Published: October 2012

AbstractAbstractColloid cysts are rare congenital, intracranial neoplasms, commonly located in the third ventricle. Colloid cysts are endodermal congenital malformations. The cysts commonly range in size from 1–2 cm in diameter, although large cysts >3 cm in size have been reported. The components of the cyst include an outer fibrous capsule over an inner epithelium. The epithelium is usually a single layer of mucin-producing or ciliated cells. Such cysts contain mucoid and gelatinous material, which is positive for both Periodic acid Schiff (PAS) and mucicarmen staining. Although colloid cysts usually represent histopathologically benign neoplasms, they can result in sudden, unexpected and potentially lethal complications. The mechanism(s) of death is still a controversial subject and several mechanisms have been postulated to explain the sudden onset of severe symptoms and of fatal rapid deterioration in patients with colloid cysts. In this case, macroscopic and histological findings addressed the diagnosis of colloid cyst of the third ventricle with diffuse myocardial injury (coagulative myocytolysis or contraction band necrosis, CBN) and led us to conclude that acute cardiac arrest due to hypothalamus stimulation in the context of colloid cyst of the third ventricle was the cause of death. As the hypothalamic structures which are involved in neuroendocrine and autonomic regulation playing a key role in cardiovascular control are located close to the walls of the third ventricle which is the most frequent anatomical site of colloid cyst, this may suggest that reflex cardiac effects due to the compression of the hypothalamic cardiovascular regulatory centers by the cyst explain the sudden death in patients harboring a colloid cyst when signs of hydrocephalus or brain herniation are lacking.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/4915842848034158
Radiotherapy is associated with significant improvement in local and regional control in Merkel cell carcinoma
Authors: Kang Susan H , Haydu Lauren E , Goh Robin Yeong Hong , Fogarty Gerald B 
Published: October 2012

Abstract

Introduction
Merkel cell carcinoma (MCC) is a rare tumour of skin. This study is a retrospective audit of patients with MCC from St Vincent’s and Mater Hospital, Sydney, Australia. The aim of this study was to investigate the influence of radiotherapy (RT) on the local and regional control of MCC lesions and survival of patients with MCC.

Method
The data bases in anatomical pathology, RT and surgery. We searched for patients having a diagnosis of MCC between 1996 and 2007. Patient, tumour and treatment characteristics were collected and analysed. Univariate survival analysis of categorical variables was conducted with the Kaplan-Meier method together with the Log-Rank test for statistical significance. Continuous variables were assessed using the Cox regression method. Multivariate analysis was performed for significant univariate results.

Results
Sixty seven patients were found. Sixty two who were stage I-III and were treated with radical intent were analysed. 68% were male. The median age was 74 years. Forty-two cases (68%) were stage I or II, and 20 cases (32%) were stage III. For the subset of 42 stage I and II patients, those that had RT to their primary site had a 2-year local recurrence free survival of 89% compared with 36% for patients not receiving RT (p<0.001). The cumulative 2-year regional recurrence free survival for patients having adjuvant regional RT was 84% compared with 43% for patients not receiving this treatment (p<0.001). Immune status at initial surgery was a significant predictor for OS and MCCSS. In a multivariate analysis combining macroscopic size (mm) and immune status at initial surgery, only immune status remained a significant predictor of overall survival (HR=2.096, 95% CI: 1.002-4.385, p=0.049).

Conclusions
RT is associated with significant improvement in local and regional control in Merkel cell carcinoma. Immunosuppression is an important factor in overall survival.
The viral transactivator HBx protein exhibits a high potential for regulation via phosphorylation through an evolutionarily conserved mechanism
Authors: Hernández Sergio , Venegas Mauricio , Brahm Javier , Villanueva Rodrigo A 
Published: October 2012

AbstractBackgroundHepatitis B virus (HBV) encodes an oncogenic factor, HBx, which is a multifunctional protein that can induce dysfunctional regulation of signaling pathways, transcription, and cell cycle progression, among other processes, through interactions with target host factors. The subcellular localization of HBx is both cytoplasmic and nuclear. This dynamic distribution of HBx could be essential to the multiple roles of the protein at different stages during HBV infection. Transactivational functions of HBx may be exerted both in the nucleus, via interaction with host DNA-binding proteins, and in the cytoplasm, via signaling pathways. Although there have been many studies describing different pathways altered by HBx, and its innumerable binding partners, the molecular mechanism that regulates its different roles has been difficult to elucidate.MethodsIn the current study, we took a bioinformatics approach to investigate whether the viral protein HBx might be regulated via phosphorylation by an evolutionarily conserved mechanism.ResultsWe found that the phylogenetically conserved residues Ser25 and Ser41 (both within the negative regulatory domain), and Thr81 (in the transactivation domain) are predicted to be phosphorylated. By molecular 3D modeling of HBx, we further show these residues are all predicted to be exposed on the surface of the protein, making them easily accesible to these types of modifications. Furthermore, we have also identified Yin Yang sites that might have the potential to be phosphorylated and O-β-GlcNAc interplay at the same residues.ConclusionsThus, we propose that the different roles of HBx displayed in different subcellular locations might be regulated by an evolutionarily conserved mechanism of posttranslational modification, via phosphorylation.
Relapsed acute promyelocytic leukemia in a hemodialysis-dependent patient treated with arsenic trioxide: a case report
Authors: Emmons Gregory S , Steingart Richard H , Stewart James A , Mertens Wilson C 
Published: October 2012

Abstract

Introduction
In the relapsed setting, arsenic trioxide remains the backbone of treatment. Scant literature exists regarding treatment of relapsed acute promyelocytic leukemia in patients with renal failure. To the best of our knowledge we are the first to report a safe and effective means of treatment for relapsed acute promyelocytic leukemia in the setting of advanced renal failure, employing titration of arsenic trioxide based on clinical parameters rather than arsenic trioxide levels.

Case presentation
A 33-year-old Caucasian man with a history of acute promyelocytic leukemia in remission for 3 years, as well as dialysis-dependent chronic renal failure secondary to a solitary kidney and focal segmental glomerulosclerosis and human immunodeficiency virus infection, receiving highly active antiretroviral therapy presented to our hospital with bone marrow biopsy-confirmed relapsed acute promyelocytic leukemia. Arsenic trioxide was begun at a low dose with dose escalation based only on side effect profile monitoring and not laboratory testing for induction as well as maintenance without undue toxicity. Our patient achieved and remains in complete hematologic and molecular remission as of this writing.

Conclusion
Arsenic trioxide can be used safely and effectively to treat acute promyelocytic leukemia in patients with advanced renal failure using careful monitoring of side effects rather than blood levels of arsenic to guide therapeutic dosing.
Health-related quality of life in women with endometriosis: a systematic review
Authors: Jia Shuang-zheng , Leng Jin-hua , Shi Jing-hua , Sun Peng-ran , Lang Jing-he 
Published: October 2012

Abstract
Endometriosis has critical implications for women’s quality of life. However, an overview of the current knowledge of this issue is limited. The objective of this systematic review was to determine the extent of endometriosis and its treatment upon women’s health-related quality of life (HRQoL). PubMed, Embase, PsycoINFO, CINAHL and the Cochrane Clinical Trials were searched up to May 2012, and only studies using standardized instruments to evaluate HRQoL in women with endometriosis were selected. Our electronic searches identified 591 citations, of which 39 studies satisfied the inclusion criteria including nine qualitative studies and 30 treatment-related studies. Findings showed that endometriosis impaired women’s HRQoL. Pain was strongly related to a poor HRQoL, and medical or surgical treatment could partially restore this impairment. No conclusive evidence was available on whether endometriosis imposed an additional impairment in HRQoL per se, apart from the decrease caused by chronic pelvic pain, or on the superiority of various hormonal suppression agents. The impacts of disease extent, duration and fertility status upon HRQoL were inconsistent. In summary, HRQoL was impaired in women with endometriosis, and medical or surgical treatment to alleviate pain could partially restore this impairment.
Glucagon-Like Peptide-1 Counteracts Oxidative Stress-Dependent Apoptosis of Human Cardiac Progenitor Cells by Inhibiting the Activation of the c-Jun N-terminal Protein Kinase Signaling Pathway
Authors: Laviola L. , Leonardini A. , Melchiorre M. , Orlando M. R. , Peschechera A. , Bortone A. , Paparella D. , Natalicchio A. , Perrini S. , Giorgino F. 
Published: October 2012

AbstractIncreased apoptosis of cardiac progenitor cells (CPCs) has been proposed as a mechanism of myocardial damage and dysfunction. Glucagon-like peptide-1 (GLP-1) has been shown to improve heart recovery and function after ischemia and to promote cell survival. The protective effects of GLP-1 on oxidative stress-induced apoptosis were investigated in human CPCs isolated from human heart biopsies. Mesenchymal-type cells were isolated from human heart biopsies, exhibited the marker profile of CPCs, differentiated toward the myocardiocyte, adipocyte, chondrocyte, and osteocyte lineages under appropriate culture conditions, and expressed functional GLP-1 receptors. CPCs were incubated with GLP-1 with or without hydrogen peroxide (H2O2). Phospho- and total proteins were detected by immunoblotting and immunofluorescence analysis. Gene expression was evaluated by quantitative RT-PCR. The role of the canonical GLP-1 receptor was assessed by using the receptor antagonist exendin(9–39) and receptor-specific silencer small interfering RNAs. Cell apoptosis was quantified by an ELISA assay and by flow cytometry-detected Annexin V. Exposure of CPCs to H2O2 induced a 2-fold increase in cell apoptosis, mediated by activation of the c-Jun N-terminal protein kinase (JNK) pathway. Preincubation of CPCs with GLP-1 avoided H2O2-triggered JNK phosphorylation and nuclear localization, and protected CPCs from apoptosis. The GLP-1 effects were markedly reduced by coincubation with the receptor antagonist exendin(9–39), small interfering RNA-mediated silencing of the GLP-1 receptor, and pretreatment with the protein kinase A inhibitor H89. In conclusion, activation of GLP-1 receptors prevents oxidative stress-mediated apoptosis in human CPCs by interfering with JNK activation and may represent an important mechanism for the cardioprotective effects of GLP-1.
Adiponectin Deficit During the Precarious Glucose Economy of Early Lactation in Dairy Cows
Authors: Giesy Sarah L. , Yoon Bohyung , Currie W. Bruce , Kim Jin Wook , Boisclair Yves R. 
Published: October 2012

AbstractIn rodents and primates, insulin resistance develops during pregnancy and fades after parturition. In contrast, dairy cows and other ruminants maintain insulin resistance in early lactation (EL). This adaptation favors mammary glucose uptake, an insulin-independent process, at a time when the glucose supply is scarce. Reduction in circulating levels of the insulin-sensitizing hormone adiponectin promotes insulin resistance in other species, but whether it contributes to insulin resistance in EL dairy cows is unknown. To address this question, plasma adiponectin was measured in high-yielding dairy cows during the transition from late pregnancy (LP) to EL. Plasma adiponectin varied in quadratic fashion with the highest levels in LP, a maximal reduction of 45% on the day after parturition and a progressive return to LP values over the next 8 wk. Adiponectin circulated nearly exclusively in high molecular weight complexes in LP, and this distribution remained unaffected in EL. The reduction of plasma adiponectin in EL occurred without changes in adiponectin mRNA in adipose tissue but was associated with repression of the expression of proteins associated with the endoplasmic reticulum and involved in assembly of adiponectin oligomers. Finally, EL increased the expression of the adiponectin receptor 1 in muscle and adiponectin receptor 2 in liver but had no effect on the expression of these receptors in adipose tissue and in the mammary gland. These data suggest that reduced plasma adiponectin belongs to the subset of hormonal adaptations in EL dairy cows facilitating mammary glucose uptake via promotion of insulin resistance.
Dual Effect of 17β-Estradiol on NMDA-Induced Neuronal Death: Involvement of Metabotropic Glutamate Receptor 1
Authors: Spampinato Simona Federica , Merlo Sara , Molinaro Gemma , Battaglia Giuseppe , Bruno Valeria , Nicoletti Ferdinando , Sortino Maria Angela 
Published: October 2012

AbstractPretreatment with 10 nm 17β-estradiol (17βE2) or 100 μm of the metabotropic glutamate 1 receptor (mGlu1R) agonist, dihydroxyphenylglycine (DHPG), protected neurons against N-methyl-d-aspartate (NMDA) toxicity. This effect was sensitive to blockade of both estrogen receptors and mGlu1R by their respective antagonists. In contrast, 17βE2 and/or DHPG, added after a low-concentration NMDA pulse (45 μm), produced an opposite effect, i.e. an exacerbation of NMDA toxicity. Again this effect was prevented by both receptor antagonists. In support of an interaction of estrogen receptors and mGlu1R in mediating a neurotoxic response, exacerbation of NMDA toxicity by 17βE2 disappeared when cultures were treated with DHPG prior to NMDA challenge, and conversely, potentiation of NMDA-induced cell death by DHPG was prevented by pretreatment with 17βE2. Addition of calpain III inhibitor (10 μm), 2 h before NMDA, prevented the increased damage induced by the two agonists, an affect that can be secondary to cleavage of mGlu1R by calpain. Accordingly, NMDA stimulation reduced expression of the full-length (140 kDa) mGluR1, an effect partially reversed by calpain inhibitor. Finally, in the presence of NMDA, the ability of 17βE2 to stimulate phosphorylation of AKT and ERK was impaired. Pretreatment with calpain inhibitor prevented the reduction of phosphorylated ERK but had no significant effect on phosphorylated AKT. Accordingly, the inhibition of ERK signaling by U0126 (1 μm) counteracted the effect of calpain inhibition on 17βE2-induced exacerbation of NMDA toxicity. The present data confirm the dual role of estrogens in neurotoxicity/neuroprotection and highlight the role of the timing of exposure to estrogens.
Tetraspan TM4SF5-dependent direct activation of FAK and metastatic potential of hepatocarcinoma cells
Authors: Jung Oisun , Choi Suyong , Jang Sun-Bok , Lee Sin-Ae , Lim Ssang-Taek , Choi Yoon-Ju , Kim Hye-Jin , Kim Do-Hee , Kwak Tae Kyoung , Kim Hyeonjung , Kang Minkyung , Lee Mi-Sook , Park Sook Young , Ryu Jihye , Jeong Doyoung , Cheong Hae-Kap , Kim Hyun Jeong , Park Ki Hun , Lee Bong-Jin , Schlaepfer David D. , Lee Jung Weon 
Published: October 2012

Summary
Transmembrane 4 L six family member 5 (TM4SF5) plays an important role in cell migration, and focal adhesion kinase (FAK) activity is essential for homeostatic and pathological migration of adherent cells. However, it is unclear how TM4SF5 signaling mediates the activation of cellular migration machinery, and how FAK is activated during cell adhesion. Here, we showed that direct and adhesion-dependent binding of TM4SF5 to FAK causes a structural alteration that may release the inhibitory intramolecular interaction in FAK. In turn, this may activate FAK at the cell's leading edge, to promote migration/invasion and in vivo metastasis. TM4SF5-mediated FAK activation occurred during integrin-mediated cell adhesion. TM4SF5 was localized at the leading edge of the cells, together with FAK and actin-organizing molecules, indicating a signaling link between TM4SF5/FAK and actin reorganization machinery. Impaired interactions between TM4SF5 and FAK resulted in an attenuated FAK phosphorylation (the signaling link to actin organization machinery) and the metastatic potential. Our findings demonstrate that TM4SF5 directly binds to and activates FAK in an adhesion-dependent manner, to regulate cell migration and invasion, suggesting that TM4SF5 is a promising target in the treatment of metastatic cancer.
Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency
Authors: Pasque Vincent , Radzisheuskaya Aliaksandra , Gillich Astrid , Halley-Stott Richard P. , Panamarova Maryna , Zernicka-Goetz Magdalena , Surani M. Azim , Silva José C. R. 
Published: October 2012

Summary
How cell fate becomes restricted during somatic cell differentiation is a long-lasting question in biology. Epigenetic mechanisms not present in pluripotent cells and acquired during embryonic development are expected to stabilize the differentiated state of somatic cells and thereby restrict their ability to convert to another fate. The histone variant macroH2A acts as a component of an epigenetic multilayer that heritably maintains the silent X chromosome and has been shown to restrict tumor development. Here we show that macroH2A marks the differentiated cell state during mouse embryogenesis. MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development. Chromatin immunoprecipitation revealed that macroH2A.1 is incorporated in the chromatin of regulatory regions of pluripotency genes in somatic cells such as mouse embryonic fibroblasts and adult neural stem cells, but not in embryonic stem cells. Removal of macroH2A.1, macroH2A.2 or both increased the efficiency of induced pluripotency up to 25-fold. The obtained induced pluripotent stem cells reactivated pluripotency genes, silenced retroviral transgenes and contributed to chimeras. In addition, overexpression of macroH2A isoforms prevented efficient reprogramming of epiblast stem cells to naïve pluripotency. In summary, our study identifies for the first time a link between an epigenetic mark and cell fate restriction during somatic cell differentiation, which helps to maintain cell identity and antagonizes induction of a pluripotent stem cell state.
Mechanisms of transepithelial ammonia excretion and luminal alkalinization in the gut of an intestinal air-breathing fish, Misgurnus anguilliacaudatus
Authors: Wilson Jonathan M. , Moreira-Silva Joana C. , Delgado Inês L. S. , Ebanks Sue C. , Vijayan Mathilakath M. , Coimbra João , Grosell Martin 
Published: October 2012

Summary
The weatherloach, Misgurnus angulliacaudatus, is an intestinal air-breathing, freshwater fish that has the unique ability to excrete ammonia through gut volatilization when branchial and cutaneous routes are compromised during high environmental ammonia or air exposure. We hypothesized that transepithelial gut NH4+ transport is facilitated by an apical Na+/H+ (NH4+) exchanger (NHE) and basolateral Na+/K+(NH4+)-ATPase, and that gut boundary layer alkalinization (NH4+ =&gt; NH3 + H+) is facilitated by apical HCO3- secretion through a Cl-/HCO3- anion exchanger. This was tested using a pharmacological approach with anterior (digestive) and posterior (respiratory) intestine preparations mounted in pH-stat equipped Ussing chambers. The anterior intestine had a markedly higher conductance, short circuit current and net base (Jbase) and ammonia excretions rates (Jamm) than posterior intestine. In anterior intestine, HCO3- accounted for 70% Jbase. In the presence of an imposed serosal-mucosal ammonia gradient, both NHE and Na+/K+-ATPase inhibitors EIPA (0.1mM) and ouabain (0.1mM) significantly inhibit Jamm in the anterior intestine, although only the former in the posterior intestine. In addition, the anion exchange inhibitor DIDS significantly reduced Jbase in anterior intestine although only at a high dose (1mM). Carbonic anhydrase does not appear to be associated with gut alkalization under these conditions since etoxzolamide was without effect on Jbase. Membrane fluidity of the posterior intestine was low suggesting low permeability, which was also reflected in a lower mucosal-serosal Jamm in the presence of an imposed gradient in contrast to the anterior intestine. To conclude although the posterior intestine is highly modified for gas exchange, it is the anterior intestine that is the likely site of ammonia excretion and alkalinization leading to ammonia volatilization in the gut.