bluuebunny/crossref_metadata_2025_split huggingface dataset:
Marked potentiation of cell swelling by cytokines in ammonia-sensitized cultured astrocytes
Authors: Rama Rao Kakulavarapu V , Jayakumar Arumugam R , Tong Xiaoying , Alvarez Veronica M , Norenberg Michael D 
Published: October 2010

AbstractBackgroundBrain edema leading to high intracranial pressure is a lethal complication of acute liver failure (ALF), which is believed to be cytotoxic due to swelling of astrocytes. In addition to the traditional view that elevated levels of blood and brain ammonia are involved in the mechanism of brain edema in ALF, emerging evidence suggests that inflammatory cytokines also contribute to this process. We earlier reported that treatment of astrocyte cultures with a pathophysiological concentration of ammonia (5 mM NH4Cl) resulted in the activation of nuclear factor-kappaB (NF-κB) and that inhibition of such activation diminished astrocyte swelling, suggesting a key role of NF-κB in the mechanism of ammonia-induced astrocyte swelling. Since cytokines are also well-known to activate NF-κB, this study examined for additive/synergistic effects of ammonia and cytokines in the activation of NF-κB and their role in astrocyte swelling.MethodsPrimary cultures of astrocytes were treated with ammonia and cytokines (TNF-α, IL-1, IL-6, IFN-γ, each at 10 ng/ml), individually or in combination, and cell volume was determined by the [3H]-O-methylglucose equilibration method. The effect of ammonia and cytokines on the activation of NF-κB was determined by immunoblots.ResultsCell swelling was increased by ammonia (43%) and by cytokines (37%) at 24 h. Simultaneous co-treatment with cytokines and ammonia showed no additional swelling. By contrast, cultures pretreated with ammonia for 24 h and then exposed to cytokines for an additional 24 h, showed a marked increase in astrocyte swelling (129%). Treatment of cultures with ammonia or cytokines alone also activated NF-κB (80-130%), while co-treatment had no additive effect. However, in cultures pre-treated with ammonia for 24 h, cytokines induced a marked activation of NF-κB (428%). BAY 11-7082, an inhibitor of NF-κB, completely blocked the astrocyte swelling in cultures pre-treated with ammonia and followed by the addition of a mixture of cytokines.ConclusionOur results indicate that ammonia and a mixture of cytokines each cause astrocyte swelling but when these agents are added simultaneously, no additive effects were found. On the other hand, when cells were initially treated with ammonia and 24 h later given a mixture of cytokines, a marked potentiation in cell swelling and NF-κB activation occurred. These data suggest that the potentiation in cell swelling is a consequence of the initial activation of NF-κB by ammonia. These findings provide a likely mechanism for the exacerbation of brain edema in patients with ALF in the setting of sepsis/inflammation.
Effect of a short-term HAART on SIV load in macaque tissues is dependent on time of initiation and antiviral diffusion
Authors: Bourry Olivier , Mannioui Abdelkrim , Sellier Pierre , Roucairol Camille , Durand-Gasselin Lucie , Dereuddre-Bosquet Nathalie , Benech Henri , Roques Pierre , Le Grand Roger 
Published: October 2010

AbstractBackgroundHIV reservoirs are rapidly established after infection, and the effect of HAART initiated very early during acute infection on HIV reservoirs remains poorly documented, particularly in tissue known to actively replicate the virus. In this context, we used the model of experimental infection of macaques with pathogenic SIV to assess in different tissues: (i) the effect of a short term HAART initiated at different stages during acute infection on viral dissemination and replication, and (ii) the local concentration of antiviral drugs.ResultsHere, we show that early treatment with AZT/3TC/IDV initiated either within 4 hours after intravenous infection of macaques with SIVmac251 (as a post exposure prophylaxis) or before viremia peak (7 days post-infection [pi]), had a strong impact on SIV production and dissemination in all tissues but did not prevent infection. When treatment was initiated after the viremia peak (14 days pi) or during early chronic infection (150 days pi), significant viral replication persists in the peripheral lymph nodes and the spleen of treated macaques despite a strong effect of treatment on viremia and gut associated lymphoid tissues. In these animals, the level of virus persistence in tissues was inversely correlated with local concentrations of 3TC: high concentrations of 3TC were measured in the gut whereas low concentrations were observed in the secondary lymphoid tissues. IDV, like 3TC, showed much higher concentration in the colon than in the spleen. AZT concentration was below the quantification threshold in all tissues studied.ConclusionsOur results suggest that limited antiviral drug diffusion in secondary lymphoid tissues may allow persistent viral replication in these tissues and could represent an obstacle to HIV prevention and eradication.
Relative replication capacity of phenotypic SIV variants during primary infections differs with route of inoculation
Authors: Biesinger Tasha , White Robert , Yu Kimata Monica T , Wilson Brenda K , Allan Jonathan S , Kimata Jason T 
Published: October 2010

Abstract

Background
Previous studies of human and simian immunodeficiency virus (HIV and SIV) have demonstrated that adaptive mutations selected during the course of infection alter viral replicative fitness, persistence, and pathogenicity. What is unclear from those studies is the impact of transmission on the replication and pathogenicity of the founding virus population. Using the SIV-macaque model, we examined whether the route of infection would affect the establishment and replication of two SIVmne variants of distinct in vitro and in vivo biological characteristics. For these studies, we performed dual-virus inoculations of pig-tailed macaques via intrarectal or intravenous routes with SIVmneCl8, a miminally pathogenic virus, and SIVmne027, a highly pathogenic variant that replicates more robustly in CD4+ T cells.

Results
The data demonstrate that SIVmne027 is the dominant virus regardless of the route of infection, indicating that the capacity to replicate efficiently in CD4+ T cells is important for fitness. Interestingly, in comparison to intravenous co-infection, intrarectal inoculation enabled greater relative replication of the less pathogenic virus, SIVmneCl8. Moreover, a higher level of SIVmneCl8 replication during primary infection of the intrarectally inoculated macaques was associated with lower overall plasma viral load and slower decline in CD4+ T cells, even though SIVmne027 eventually became the dominant virus.

Conclusions
These results suggest that the capacity to replicate in CD4+ T cells is a significant determinant of SIV fitness and pathogenicity. Furthermore, the data also suggest that mucosal transmission may support early replication of phenotypically diverse variants, while slowing the rate of CD4+ T cell decline during the initial stages of infection.
Biodiversity of Archaea and floral of two inland saltern ecosystems in the Alto Vinalopó Valley, Spain
Authors: Zafrilla Basilio , Martínez-Espinosa Rosa M , Alonso María A , Bonete María J 
Published: October 2010

AbstractBackgroundThe extraction of salt from seawater by means of coastal solar salterns is a very well-described process. Moreover, the characterization of these environments from ecological, biochemical and microbiological perspectives has become a key focus for many research groups all over the world over the last 20 years. In countries such as Spain, there are several examples of coastal solar salterns (mainly on the Mediterranean coast) and inland solar salterns, from which sodium chloride is obtained for human consumption. However, studies focused on the characterization of inland solar salterns are scarce and both the archaeal diversity and the plant communities inhabiting these environments remain poorly described.ResultsTwo of the inland solar salterns (termed Redonda and Penalva), located in the Alto Vinalopó Valley (Alicante, Spain), were characterized regarding their geological and physico-chemical characteristics and their archaeal and botanical biodiversity. A preliminary eukaryotic diversity survey was also performed using saline water. The chemical characterization of the brine has revealed that the salted groundwater extracted to fill these inland solar salterns is thalassohaline. The plant communities living in this environment are dominated bySarcocornia fruticosa(L.) A.J. Scott,Arthrocnemum macrostachyum(Moris) K. Koch,Suaeda veraForsk. ex Gmelin (Amaranthaceae) and several species ofLimonium(Mill) andTamarix(L). Archaeal diversity was analyzed and compared by polymerase chain reaction (PCR)-based molecular phylogenetic techniques. Most of the sequences recovered from environmental DNA samples are affiliated with haloarchaeal genera such asHaloarcula, Halorubrum, HaloquadratumandHalobacterium, and with an unclassified member of the Halobacteriaceae. The eukaryoteDunaliellawas also present in the samples.ConclusionsTo our knowledge, this study constitutes the first analysis centered on inland solar salterns located in the southeastern region of Spain. The results obtained revealed that the salt deposits of this region have marine origins. Plant communities typical of salt marshes are present in this ecosystem and members of theHalobacteriaceaefamily can be easily detected in the microbial populations of these habitats. Possible origins of the haloarchaea detected in this study are discussed.
Risk of classical Kaposi sarcoma by plasma levels of Epstein-Barr virus antibodies, sCD26, sCD23 and sCD30
Authors: Pelser Colleen , Middeldorp Jaap , Mbulaiteye Sam M , Lauria Carmela , Messina Angelo , Viviano Enza , Romano Nino , Vitale Francesco , Goedert James J 
Published: October 2010

AbstractBackgroundTo clarify the immunological alterations leading to classical Kaposi sarcoma (cKS) among people infected with KS-associated herpesvirus (KSHV).MethodsIn a population-based study of 119 cKS cases, 105 KSHV-seropositive controls, and 155 KSHV-seronegative controls, we quantified plasma soluble cluster of differentiation (sCD) levels and antibodies against Epstein-Barr virus nuclear antigen-1 (anti-EBNA-1) and viral capsid antigen (anti-VCA). Differences between groups in prevalence of low-tertile anti-EBNA-1 and high-tertile anti-VCA were compared by logistic regression. Continuous levels between groups and by presence of cKS co-factors among controls were compared by linear regression and Mann-Whitney-Wilcoxon methods.ResultsComparisons of cKS cases to seropositive controls and of seropositive to seronegative controls revealed no significant differences. However, controls with known cKS cofactors (male sex, nonsmoking, diabetes and cortisone use) had significantly lower levels of anti-EBNA (P= 0.0001 - 0.07) and anti-VCA (P= 0.0001 - 0.03). Levels of sCD26 were significantly lower for male and non-smoking controls (Padj≤ 0.03), and they were marginally lower with older age and cortisone use (Padj≤ 0.09).ConclusionsAnti-EBV and sCD26 levels were associated with cofactors for cKS, but they did not differ between cKS cases and matched controls. Novel approaches and broader panels of assays are needed to investigate immunological contributions to cKS.
Parasites in Mexican patients with irritable bowel syndrome: a case-control study
Authors: Ramirez-Miranda Maria Elena , Hernandez-Castellanos Rosaura , Lopez-Escamilla Eduardo , Moncada David , Rodriguez-Magallan Alfredo , Pagaza-Melero Carlos , Gonzalez-Angulo Alberto , Flisser Ana , Kawa-Karasik Simon , Maravilla Pablo 
Published: October 2010

Abstract
One hundred and fifteen patients with symptoms suggestive of irritable bowel syndrome (IBS) according to Rome III criteria and 209 patients with gastrointestinal symptoms different from IBS (control) were identified through medical records from the Gastroenterology Clinic of the "Dr. Manuel Gea Gonzalez General Hospital" from January 2008 to March 2010. No statistical differences in IBS data as compared with control groups were observed except in bloating, that was more frequent in the IBS group (P = 0.043). Although the pathogenicity of specific intestinal protozoa could not be demonstrated due to lack of association with the development of gastrointestinal symptoms, Blastocystis spp, in the IBS group, exhibited a trend of association to diarrhoea (odds ratio = 2.73, 95% confidence interval = 0.84-8.80, P = 0.053), while having any parasite and diarrhoea was significant (odds ratio = 3.38, 95% confidence interval = 1.33-8.57, P = 0.008). The association between Blastocystis and diarrhoea in IBS patients although not conclusive is an interesting finding; nonetheless more extensive case-controlled studies are required to clearly define the role of some "non-pathogenic" parasites in intestinal disease and IBS.
Urine interleukin-6 is an early biomarker of acute kidney injury in children undergoing cardiac surgery
Authors: Dennen Paula , Altmann Christopher , Kaufman Jonathan , Klein Christina L , Andres-Hernando Ana , Ahuja Nilesh H , Edelstein Charles L , Cadnapaphornchai Melissa A , Keniston Angela , Faubel Sarah 
Published: October 2010

AbstractIntroductionInterleukin-6 (IL-6) is a proinflammatory cytokine that increases early in the serum of patients with acute kidney injury (AKI). The aim of this study was to determine whether urine IL-6 is an early biomarker of AKI and determine the source of urine IL-6. Numerous proteins, including cytokines, are filtered by the glomerulus and then endocytosed and metabolized by the proximal tubule. Since proximal tubule injury is a hallmark of AKI, we hypothesized that urine IL-6 would increase in AKI due to impaired proximal tubule metabolism of filtered IL-6.MethodsUrine was collected in 25 consecutive pediatric patients undergoing cardiac bypass surgery (CPB). AKI was defined as a 50% increase in serum creatinine at 24 hours (RIFLE (Risk, Injury, Failure, Loss, End stage), R). Mouse models of AKI and freshly isolated proximal tubules were also studied.ResultsUrine IL-6 increased at six hours in patients with AKI versus no AKI (X2= 8.1750;P< 0.0042). Urine IL-6 > 75 pg/mg identified AKI with a sensitivity of 88%. To assess whether increased urine IL-6 occurs in functional versus structural renal failure, mouse models of pre-renal azotemia after furosemide injection (no tubular injury), ischemic AKI (tubular injury) and cisplatin AKI (tubular injury) were studied. Urine IL-6 did not significantly increase in pre-renal azotemia but did increase in ischemic and cisplatin AKI. To determine if circulating IL-6 appears in the urine in AKI, recombinant human (h)IL-6 was injected intravenously and urine collected for one hour; urine hIL-6 increased in ischemic AKI, but not pre-renal azotemia. To determine the effect of AKI on circulating IL-6, serum hIL-6 was determined one hour post-intravenous injection and was increased in ischemic AKI, but not pre-renal azotemia. To directly examine IL-6 metabolism, hIL-6 was added to the media of normal and hypoxic isolated proximal tubules; hIL-6 was reduced in the media of normal versus injured hypoxic proximal tubules.ConclusionsUrine IL-6 increases early in patients with AKI. Animal studies demonstrate that failure of proximal tubule metabolism of IL-6 results in increased serum and urine IL-6. Impaired IL-6 metabolism leading to increased serum IL-6 may contribute to the deleterious systemic effects and increased mortality associated with AKI.
The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis
Authors: Shapiro Nathan I , Schuetz Philipp , Yano Kiichiro , Sorasaki Midori , Parikh Samir M , Jones Alan E , Trzeciak Stephen , Ngo Long , Aird William C 
Published: October 2010

Abstract
Introduction
Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death.

Methods
This is a prospective, observational study including adult patients (age 18 years or older) presenting with clinical suspicion of infection to the emergency department (ED) of an urban, academic medical center between February 2005 and November 2008. Blood was sampled during the ED visit and biomarkers of endothelial cell activation, namely soluble fms-like tyrosine kinase-1 (sFlt-1), plasminogen activator inhibitors -1 (PAI-1), sE-selectin, soluble intercellular adhesion molecule (sICAM-1), and soluble vascular cell adhesion molecule (sVCAM-1), were assayed. The association between biomarkers and the outcomes of sepsis severity, organ dysfunction, and in-hospital mortality were analyzed.

Results
A total of 221 patients were included: sepsis without organ dysfunction was present in 32%, severe sepsis without shock in 30%, septic shock in 32%, and 6% were non-infected control ED patients. There was a relationship between all target biomarkers (sFlt-1, PAI-1, sE-selectin, sICAM-1, and sVCAM-1) and sepsis severity, P < 0.05. We found a significant inter-correlation between all biomarkers, including the strongest correlations between sFlt-1 and sE-selectin (r = 0.55, P < 0.001), and between sFlt-1 and PAI-1 (0.56, P < 0.001). Among the endothelial cell activation biomarkers, sFlt-1 had the strongest association with SOFA score (r = 0.66, P < 0.001), the highest area under the receiver operator characteristic curve for severe sepsis of 0.82, and for mortality of 0.91.

Conclusions
Markers of endothelial cell activation are associated with sepsis severity, organ dysfunction and mortality. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.
Somatic structural rearrangements in genetically engineered mouse mammary tumors
Authors: Varela Ignacio , Klijn Christiaan , Stephens Phillip J , Mudie Laura J , Stebbings Lucy , Galappaththige Danushka , van der Gulden Hanneke , Schut Eva , Klarenbeek Sjoerd , Campbell Peter J , Wessels Lodewyk FA , Stratton Michael R , Jonkers Jos , Futreal P Andrew , Adams David J 
Published: October 2010

Abstract
Background
Here we present the first paired-end sequencing of tumors from genetically engineered mouse models of cancer to determine how faithfully these models recapitulate the landscape of somatic rearrangements found in human tumors. These were models of Trp53-mutated breast cancer, Brca1- and Brca2-associated hereditary breast cancer, and E-cadherin (Cdh1) mutated lobular breast cancer.

Results
We show that although Brca1- and Brca2-deficient mouse mammary tumors have a defect in the homologous recombination pathway, there is no apparent difference in the type or frequency of somatic rearrangements found in these cancers when compared to other mouse mammary cancers, and tumors from all genetic backgrounds showed evidence of microhomology-mediated repair and non-homologous end-joining processes. Importantly, mouse mammary tumors were found to carry fewer structural rearrangements than human mammary cancers and expressed in-frame fusion genes. Like the fusion genes found in human mammary tumors, these were not recurrent. One mouse tumor was found to contain an internal deletion of exons of the Lrp1b gene, which led to a smaller in-frame transcript. We found internal in-frame deletions in the human ortholog of this gene in a significant number (4.2%) of human cancer cell lines.

Conclusions
Paired-end sequencing of mouse mammary tumors revealed that they display significant heterogeneity in their profiles of somatic rearrangement but, importantly, fewer rearrangements than cognate human mammary tumors, probably because these cancers have been induced by strong driver mutations engineered into the mouse genome. Both human and mouse mammary cancers carry expressed fusion genes and conserved homozygous deletions.
Substance P inhibits natural killer cell cytotoxicity through the neurokinin-1 receptor
Authors: Monaco-Shawver Linda , Schwartz Lynnae , Tuluc Florin , Guo Chang-Jiang , Lai Jian Ping , Gunnam Satya M , Kilpatrick Laurie E , Banerjee Pinaki P , Douglas Steven D , Orange Jordan S 
Published: October 2010

ABSTRACTSP is a potent neuroimmunomodulator that functions through ligating members of the neurokinin receptor family, one of which, NK1R, is widely expressed in immune cells. As in humans, circulating SP levels are increased in pathologic states associated with impairment of NK cell functions, such as depression and HIV infection, we hypothesized that SP has a direct, inhibitory effect upon NK cells. We have studied a clonal human NK cell line (YTS) as well as ex vivo human NK cells and have determined that truncated and full-length NK1R isoforms are expressed in and SP bound by ex vivo NK cells and the YTS NK cell line. Incubation of YTS cells with 10−6 M SP and ex vivo NK cells with 10−5 M SP inhibited cytotoxic ability by ∼20% and reduced degranulation. This inhibitory effect upon cytotoxicity was partially prevented by the NK1R antagonist CP96,345. The treatment of YTS or ex vivo NK cells with SP neither down-modulated NCR expression nor affected triggering receptor-induced NF-κB activation. Preincubation of YTS cells with SP, however, did abbreviate the typically prolonged intracellular calcium increase induced by target cell engagement and reduced triggering receptor-induced pERK. Thus, SP has the potential to regulate NK cell functions and acts downstream from neurokinin receptors to modulate NK cell activation signaling. This mechanism may contribute to impairment of NK cell function in certain disease states associated with increased circulating SP. Antagonism of this system may present an opportunity to augment NK cell function therapeutically in selected human diseases.
Serine residues in the LAT adaptor are essential for TCR-dependent signal transduction
Authors: Martínez-Florensa Mario , García-Blesa Antonio , Yélamos José , Muñoz-Suano Alba , Domínguez-Villar Margarita , Valdor Rut , Alonso Antonio , García-Cózar Francisco , Aparicio Pedro , Malissen Bernard , Aguado Enrique 
Published: October 2010

ABSTRACTThe adaptor protein LAT has a prominent role in the transduction of intracellular signals elicited by the TCR/CD3 complex. Upon TCR engagement, LAT becomes tyrosine-phosphorylated and thereby, recruits to the membrane several proteins implicated in the activation of downstream signaling pathways. However, little is known about the role of other conserved motifs present in the LAT sequence. Here, we report that the adaptor LAT contains several conserved serine-based motifs, which are essential for proper signal transduction through the TCR. Mutation of these serine motifs in the human T cell line Jurkat prevents proper calcium influx, MAPK activation, and IL-2 production in response to TCR/CD3 stimulation. Moreover, this mutant form of LAT has a reduced ability to bind to PLC-γ1 and SLP-76, although phosphorylation of tyrosine residues 132, 171, and 191 is not decreased, raising a possible role for the serine-based motifs of LAT for the binding of important partners. The functional role of LAT serine-based motifs in signal transduction could be mediated by an effect on tyrosine phosphorylation, as their mutation significantly diminishes the phosphorylation of tyrosine residue 226. In addition, these serine motifs seem to have a regulatory role, given that upon their mutation, ZAP-70 shows enhanced phosphorylation. Therefore, the LAT serine-based motifs likely regulate signaling pathways that are essential for T cell physiology.