bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of metabotropic glutamate receptor‐mediated synaptic signalling in cerebellar Purkinje cells
Authors: Hartmann J. , Konnerth A. 
Published: November 2008

AbstractThe metabotropic glutamate receptors type 1 (mGluR1s) are required for a normal function of the mammalian cerebellum. These G‐protein‐coupled receptors are abundantly expressed in the principle cerebellar cells, namely the Purkinje neurones. Under physiological conditions, mGluR1s are activated during repetitive activity of both afferent glutamatergic synaptic inputs provided by the climbing and parallel fibres respectively. Unlike the common ionotropic glutamate receptors that underlie rapid synaptic excitation, mGluR1s produce a complex post‐synaptic response consisting of a Ca2+‐release signal from intracellular stores and a slow excitatory post‐synaptic potential. While it is well established that the mGluR1‐dependent Ca2+‐release signal from intracellular stores involves the activation of inositol‐trisphosphate receptors, the mechanisms underlying the slow synaptic excitation remained unclear. Here we will review recent evidence indicating an essential role of C‐type transient receptor potential (TRPC) cation channels, especially that of the subunit TRPC3, for the generation of the mGluR1‐dependent synaptic current. For the signalling pathways underlying both, Ca2+‐release from intracellular stores and the slow synaptic potential, we present current knowledge about the activators, downstream effectors and possible roles for mGluR1‐dependent signalling in Purkinje neurones.
Measuring diffusion parameters in the brain: comparing the real‐time iontophoretic method and diffusion‐weighted magnetic resonance
Authors: Vorisek I. , Sykova E. 
Published: November 2008

AbstractThe extracellular space (ECS) diffusion parameters influence the movement of ions, neuroactive substances, hormones and metabolites in the nervous tissue. They also affect extrasynaptic transmission, a mode of signal transmission dependent solely on diffusion. This review compares in detail two methods for studying diffusion in the brain: the real‐time iontophoretic tetramethylammonium method for ECS volume fraction and tortuosity measurements and diffusion weighted‐magnetic resonance imaging for measuring the apparent diffusion coefficient of water. The results obtained using both methods under physiological conditions (post‐natal development, ageing) or in pathologies (brain injury, ischaemia) and their similarities and differences are discussed.
Neuronismo y reticulismo: neuronal–glial circuits unify the reticular and neuronal theories of brain organization
Authors: Verkhratsky A. 
Published: November 2008

AbstractThe neuronal doctrine, which shaped the development of neuroscience, was born from a long‐lasting struggle between reticularists, who assumed internal continuity of neural networks and neuronists, who defined the brain as a network of physically separated cellular entities, defined as neurones. Modern views regard the brain as a complex of constantly interacting cellular circuits, represented by neuronal networks embedded into internally connected astroglial syncytium. The neuronal–glial circuits endowed with distinct signalling cascades form a ‘diffuse nervous net’ suggested by Golgi, where millions of synapses belonging to very different neurones are integrated first into neuronal–glial–vascular units and then into more complex structures connected through glial syncytium. These many levels of integration, both morphological and functional, presented by neuronal–glial circuitry ensure the spatial and temporal multiplication of brain cognitive power.
When is high‐Ca2+ microdomain required for mitochondrial Ca2+ uptake?*
Authors: Spät A. , Fülöp L. , Koncz P. , Szanda G. 
Published: November 2008

AbstractCa2+ release from IP3‐sensitive stores in the endoplasmic reticulum (ER) induced by Ca2+‐mobilizing agonists generates high‐Ca2+ microdomains between ER vesicles and neighbouring mitochondria. Here we present a model that describes when such microdomains are required and when submicromolar [Ca2+] is sufficient for mitochondrial Ca2+ uptake. Mitochondrial Ca2+ uptake rate in angiotensin II‐stimulated H295R adrenocortical cells correlates with the proximity between ER vesicles and the mitochondrion, reflecting the uptake promoting effect of high‐Ca2+ peri‐mitochondrial microdomains. Silencing or inhibition of p38 mitogen‐activated protein kinase (MAPK) or inhibition of the novel isoforms of protein kinase C enhances mitochondrial Ca2+ uptake and abolishes the positive correlation between Ca2+ uptake and ER‐mitochondrion proximity. Inhibition of protein phosphatases attenuates mitochondrial Ca2+ uptake and also abolishes its positive correlation with ER‐mitochondrion proximity. We postulate that during IP3‐induced Ca2+ release, Ca2+ uptake is confined to ER‐close mitochondria, because of the simultaneous activation of the protein kinases. Attenuation of Ca2+ uptake prevents Ca2+ overload of mitochondria and thus protects the cell against apoptosis. On the other hand, all the mitochondria accumulate Ca2+ at a non‐inhibited rate during physiological Ca2+ influx through the plasma membrane. Membrane potential is higher in ER‐distant mitochondria, providing a bigger driving force for Ca2+ uptake. Our model explains why comparable mitochondrial Ca2+ signals are formed in response to K+ and angiotensin II (equipotent in respect to global cytosolic Ca2+ signals), although only the latter generates high‐Ca2+ microdomains.
The role of free fatty acids, pancreatic lipase and Ca2+ signalling in injury of isolated acinar cells and pancreatitis model in lipoprotein lipase‐deficient mice
Authors: Yang F. , Wang Y. , Sternfeld L. , Rodriguez J. A. , Ross C. , Hayden M. R. , Carriere F. , Liu G. , Schulz I. 
Published: November 2008

AbstractAim and methods:  Recurrent pancreatitis is a common complication of severe hypertriglyceridaemia (HTG) often seen in patients carrying various gene mutations in lipoprotein lipase (LPL). This study investigates a possible pathogenic mechanism of cell damage in isolated mouse pancreatic acinar cells and of pancreatitis in LPL‐deficient and in wild type mice.Results:  Addition of free fatty acids (FFA) or of chylomicrons to isolated pancreatic acinar cells caused stimulation of amylase release, and at higher concentrations it also caused cell damage. This effect was decreased in the presence of the lipase inhibitor orlistat. Surprisingly, pancreatic lipase whether in its active or inactive state could act like an agonist by inducing amylase secretion, increasing cellular cGMP levels and converting cell damaging sustained elevations of [Ca2+]cyt to normal Ca2+ oscillations. Caerulein increases the levels of serum amylase and caused more severe inflammation in the pancreas of LPL‐deficient mice than in wild type mice.Conclusion:  We conclude that high concentrations of FFA as present in the plasma of LPL‐deficient mice and in patients with HTG lead to pancreatic cell damage and are high risk factors for the development of acute pancreatitis. In addition to its enzymatic effect which leads to the generation of cell‐damaging FFA from triglycerides, pancreatic lipase also prevents Ca2+ overload in pancreatic acinar cells and, therefore, counteracts cell injury.
Oxygen‐dependent ion transport in erythrocytes
Authors: Bogdanova A. , Berenbrink M. , Nikinmaa M. 
Published: November 2008

AbstractThe present contribution reviews current knowledge of apparently oxygen‐dependent ion transport in erythrocytes and presents modern hypotheses on their regulatory mechanisms and physiological roles. In addition to molecular oxygen as such, reactive oxygen species, nitric oxide, carbon monoxide, regional variations of cellular ATP and hydrogen sulphide may play a role in the regulation of transport, provided that they are affected by oxygen tension. It appears that the transporter molecules themselves do not have direct oxygen sensors. Thus, the oxygen level must be sensed elsewhere, and the effect transduced to the transporter. The possible pathways involved in the regulation of transport, including haemoglobin as a sensor, and phosphorylation/dephosphorylation reactions both in the transporter and its upstream effectors, are discussed.
Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis
Authors: Um Soo‐Jung , Lee Soo‐Keol , Yang Doo Kyung , Son Choonhee , Roh Mee Sook , Kim Ki Nam , Lee Ki‐Nam , Choi Pil Jo 
Published: November 2008

AbstractIntroduction:  Although gefitinib used for the treatment of non‐small‐cell lung cancer is a well‐known cause of interstitial lung disease (ILD), few case reports on erlotinib‐induced ILD have been issued. The common risk factor of both of these two drug‐induced ILDs is idiopathic interstitial pneumonia, but ILD in a patient with radiation fibrosis has not been previously reported.Methods:  Report of a case.Results:  We recently experienced a case of fatal erlotinib‐induced ILD, diagnosed based on clinical and radiologic findings, which occurred in a patient with radiation fibrosis. A 50‐year‐old male patient was started on erlotinib as a third‐line chemotherapy. Six days after taking erlotinib, a chest radiograph showed rapid progression of reticular infiltration in both lung fields. High‐resolution computed tomography scan findings were consistent with ILD, which was sufficient to diagnose as erlotinib‐induced ILD. The patient died of respiratory failure after 8 days of steroid infusion and erlotinib discontinuation.Conclusion:  Our case shows a fatal side effect of erlotinib. This case had radiation fibrosis, so we suggest that radiation fibrosis may be another contributor of the occurrence of ILD in patients taking erlotinib.Please cite this paper as: Um S‐J, Lee S‐K, Yang DK, Son C, Roh MS, Kim KN, Lee K‐N and Choi PJ. Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis. The Clinical Respiratory Journal 2009; 3: 181–184.
Prevalence and Concentration of Verotoxigenic Escherichia coli O157:H7 in Adult Sheep at Slaughter from Italy
Authors: Franco A. , Lovari S. , Cordaro G. , Di Matteo P. , Sorbara L. , Iurescia M. , Donati V. , Buccella C. , Battisti A. 
Published: November 2008

SummaryA 1‐year study on the animal‐level prevalence and concentration of Escherichia coli O157 in adult sheep at slaughter was performed, to collect qualitative and quantitative information on the diffusion of the pathogen in adult sheep from Italy. A total 533 samples were collected, with a similar distribution in the four seasons. For prevalence estimates, a simple random sampling technique was used. An immuno‐magnetic separation technique was used for sample screening, with enumeration of the pathogen in positive samples, along with molecular and serological identification of isolates. An overall prevalence of 7.1% (38/533, 95% CI 4.9–9.3%) was observed for fully virulent E. coli O157. A wide interval of VTEC O157 per gram was observed (<100 to 6 × 105 CFU g−1), with 28.9% (11/38) of positive samples ≥1 × 103 CFU g−1, set as the threshold for those animals defined ‘active shedders’ for the purpose of the study. Eight per cent (3/38) of animals shed >1 × 104 g−1 VTEC O157, which represents >96% of the total VTEC O157 bacteria cultured from all animals tested. The prevalence estimate of active shedders was therefore 2.1% (95% CI 0.9–3.3%). Most (34/38, 89.5%) of the positive animals were found in summer (July–September). Prevalence and concentrations of virulent VTEC O157 obtained in this study contribute to the demonstration that adult sheep represent a relevant source of environmental contamination from virulent VTEC O157, as well as a source of VTEC O157 contamination for food of ovine origin (meat and dairy products), especially during warm months.
In Vitro Levels of Interleukin 10 (IL-10) and IL-12 in Response to a Recombinant 32-Kilodalton Antigen ofMycobacterium bovisBCG after Treatment for Tuberculosis
Authors: Sai Priya V. Hari , Anuradha B. , Latha Gaddam Suman , Hasnain Seyed E. , Murthy K. J. R. , Valluri Vijaya Lakshmi 
Published: November 2008

ABSTRACTCell-mediated immunity plays a major role in conferring protection against tuberculosis (TB) on an individual. It is not known whether the immune status correlates with the bacterial load or whether the immunity improves after treatment. Also, it may be important to monitor treatment by being able to discriminate between active disease and successfully treated TB. The main aim of this study was to investigate the usefulness of a recombinant 32-kDa antigen (r32-kDa Ag) ofMycobacterium bovisBCG (Ag85A-BCG) as a diagnostic marker in patients being treated for TB. Specifically, the in vitro T-cell assays and the release of interleukin-12 (IL-12) (Th1-type cytokine) and IL-10 (Th2-type cytokine) in response to the r32-kDa Ag of BCG were assayed in patients with either pulmonary (sputum positive/negative,n= 74) or extrapulmonary TB (n= 49) and healthy controls. The proliferative responses of stimulated cells at 0, 2 to 4, and 6 months of treatment increased and were highly significant (P< 0.000) compared to the responses in controls. The increase in IL-12 and decrease in IL-10 release suggest that there is cytokine expression modification during different stages of TB, and treatment seems to have an influence on the levels of these cytokines, suggesting an augmentation in the protective responses. The in vitro response to theM.bovisBCG r32-kDa Ag may be useful in monitoring treatment of TB.
Humoral and Cellular Immune Responses Induced by 3a DNA Vaccines against Severe Acute Respiratory Syndrome (SARS) or SARS-Like Coronavirus in Mice
Authors: Lu Baojing , Tao Ling , Wang Ting , Zheng Zhenhua , Li Bao , Chen Ze , Huang Yi , Hu Qinxue , Wang Hanzhong 
Published: November 2008

ABSTRACT

Vaccine development for severe acute respiratory syndrome coronavirus (SARS-CoV) has mainly focused on the spike (S) protein. However, the variation of the S gene between viruses may affect the efficacy of a vaccine, particularly for cross-protection against SARS-like CoV (SL-CoV). Recently, a more conserved group-specific open reading frame (ORF), the 3a gene, was found in both SARS-CoV and SL-CoV. Here, we studied the immunogenicity of human SARS-CoV 3a and bat SL-CoV 3a DNA vaccines in mice through electroporation immunization followed by enzyme-linked immunosorbent, enzyme-linked immunospot, and flow cytometry assays. Our results showed that high levels of specific humoral responses were induced by SARS-CoV 3a and SL-CoV 3a DNA vaccines. Furthermore, a strong Th1-based cellular immune response was stimulated by both DNA vaccines. The vaccines stimulated gamma interferon production mainly by CD8
+
T cells and interleukin-2 (IL-2) mainly by CD4
+
T cells. Of interest, the frequency of IL-2-positive cells elicited by the SARS-CoV 3a DNA vaccine was significantly higher than that elicited by the SL-CoV 3a DNA vaccine. In summary, our study provides a reference for designing cross-protective DNA vaccines based on the group-specific ORFs of CoVs.
LiveCandida albicansSuppresses Production of Reactive Oxygen Species in Phagocytes
Authors: Wellington Melanie , Dolan Kristy , Krysan Damian J. 
Published: November 2008

ABSTRACTProduction of reactive oxygen species (ROS) is an important aspect of phagocyte-mediated host responses. Since phagocytes play a crucial role in the host response toCandida albicans, we examined the ability ofCandidato modulate phagocyte ROS production. ROS production was measured in the murine macrophage cell line J774 and in primary phagocytes using luminol-enhanced chemiluminescence. J774 cells, murine polymorphonuclear leukocytes (PMN), human monocytes, and human PMN treated with liveC. albicansproduced significantly less ROS than phagocytes treated with heat-killedC. albicans. Live C.albicansalso suppressed ROS production in murine bone marrow-derived macrophages from C57BL/6 mice, but not from BALB/c mice. LiveC. albicansalso suppressed ROS in response to external stimuli.C. albicansandCandida glabratasuppressed ROS production by phagocytes, whereasSaccharomyces cerevisiaestimulated ROS production. The cell wall is the initial point of contact betweenCandidaand phagocytes, but isolated cell walls from both heat-killed and liveC. albicansstimulated ROS production. Heat-killedC. albicanshas increased surface exposure of 1,3-β-glucan, a cell wall component that can stimulate phagocytes. To determine whether surface 1,3-β-glucan exposure accounted for the difference in ROS production, liveC. albicanscells were treated with a sublethal dose of caspofungin to increase surface 1,3-β-glucan exposure. Caspofungin-treatedC. albicanswas fully able to suppress ROS production, indicating that suppression of ROS overrides stimulatory signals from 1,3-β-glucan. These studies indicate that liveC. albicansactively suppresses ROS production in phagocytes in vitro, which may represent an important immune evasion mechanism.
Toll-Like Receptor Prestimulation Increases Phagocytosis ofEscherichia coliDH5α andEscherichia coliK1 Strains by Murine Microglial Cells
Authors: Ribes Sandra , Ebert Sandra , Czesnik Dirk , Regen Tommy , Zeug Andre , Bukowski Stephanie , Mildner Alexander , Eiffert Helmut , Hanisch Uwe-Karsten , Hammerschmidt Sven , Nau Roland 
Published: November 2008

ABSTRACTMeningitis and meningoencephalitis caused byEscherichia coliare associated with high rates of mortality. When an infection occurs, Toll-like receptors (TLRs) expressed by microglial cells can recognize pathogen-associated molecular patterns and activate multiple steps in the inflammatory response that coordinate the brain's local defense, such as phagocytosis of invading pathogens. An upregulation of the phagocytic ability of reactive microglia could improve the host defense in immunocompromised patients against pathogens such asE. coli. Here, murine microglial cultures were stimulated with the TLR agonists Pam3CSK4(TLR1/TLR2), lipopolysaccharide (TLR4), and CpG oligodeoxynucleotide (TLR9) for 24 h. Upon stimulation, levels of tumor necrosis factor alpha and the neutrophil chemoattractant CXCL1 were increased, indicating microglial activation. Phagocytic activity was studied after adding eitherE. coliDH5α orE. coliK1 strains. After 60 and 90 min of bacterial exposure, the number of ingested bacteria was significantly higher in cells prestimulated with TLR agonists than in unstimulated controls (P< 0.01). Addition of cytochalasin D, an inhibitor of actin polymerization, blocked >90% of phagocytosis. We also analyzed the ability of microglia to kill the ingestedE. colistrains. Intracellularly surviving bacteria were quantified at different time points (90, 150, 240, and 360 min) after 90 min of phagocytosis. The number of bacteria killed intracellularly after 6 h was higher in cells primed with the different TLR agonists than in unstimulated microglia. Our data suggest that microglial stimulation by the TLR system can increase bacterial phagocytosis and killing. This approach could improve central nervous system resistance to infections in immunocompromised patients.
A Hemidominant
Naip5
Allele in Mouse Strain MOLF/Ei-Derived Macrophages Restricts
Legionella pneumophila
Intracellular Growth
Authors: Losick Vicki P. , Stephan Kristin , Smirnova Irina I. , Isberg Ralph R. , Poltorak Alexander 
Published: November 2008

ABSTRACT

Mouse-derived macrophages have the unique ability to restrict or permit
Legionella pneumophila
intracellular growth. The common inbred mouse strain C57BL/6J (B6) restricts
L. pneumophila
growth, whereas macrophages derived from A/J mice allow >10
3
-fold bacterial growth within three days. This phenotypic difference was mapped to the mouse
Naip5
allele. The B6 restrictive
Naip5
allele is dominant, and six amino acid changes in its product were predicted to control permissiveness. By using the wild-derived mouse strain MOLF/Ei, we found that MOLF/Ei-derived macrophages also restrict
L. pneumophila
growth, yet the Naip5 protein is identical to the A/J Naip5 at the six-amino-acid signature. The MOLF/Ei restrictive trait, unlike that of B6-derived macrophages, was not dominant over the A/J trait. In spite of this phenotypic difference, the
L. pneumophila
growth restriction in MOLF/Ei macrophages was mapped to the
Naip5
region as well, indicating that the originally predicted change in the A/J
Naip5
allele may not be critical for restriction. In the product of the A/J
Naip5
permissive allele, there are four unique amino acid changes that map to a NACHT-like domain. Similar misregulating mutations have been identified in the NACHT domains of Nod-like receptor (NLR) proteins. Therefore, one of these mutations may be critical for restriction of
L. pneumophila
intracellular growth, and this parallels results found with human NLR variants with defects in the innate immune response.
Development of an Immunochromatographic Test To Detect Antibodies against Recombinant Em18 for Diagnosis of Alveolar Echinococcosis
Authors: Sako Yasuhito , Fukuda Kenta , Kobayashi Yukuharu , Ito Akira 
Published: November 2008

ABSTRACT

An immunochromatographic test (ICT) for the rapid detection of antibodies to
Echinococcus multilocularis
was developed. The ICT showed a sensitivity of 94% and a specificity of 95.4%. High degrees of agreement were observed between the ICT and an enzyme-linked immunosorbent assay (κ = 0.93) and between the ICT and immunoblot analysis (κ = 0.97). It is expected that the ICT developed in this study will be useful for the serodiagnosis of alveolar echinococcosis.
Epstein-Barr Virus LF2: an Antagonist to Type I Interferon
Authors: Wu Liguo , Fossum Even , Joo Chul Hyun , Inn Kyung-Soo , Shin Young Chul , Johannsen Eric , Hutt-Fletcher Lindsey M. , Hass Juergen , Jung Jae U. 
Published: November 2008

ABSTRACT
Upon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated antiviral pathway, which is mediated by IFN regulatory factors (IRFs). In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Despite its association with significant human health problems, activities of Epstein-Barr virus (EBV), a human tumor-inducing herpesvirus, to evade host IFN-mediated innate immunity have not been well characterized. To search for EBV genes that block IFN signal transduction, we carried out a screening of EBV open reading frames for their abilities to block IFN-α/β-mediated luciferase expression upon Sendai virus infection. This screening demonstrates that EBV LF2 tegument protein specifically interacts with the central inhibitory association domain of IRF7, and this interaction leads to inhibition of the dimerization of IRF7, which suppresses IFN-α production and IFN-mediated immunity. This demonstrates a novel immune evasion mechanism of EBV LF2 in blocking cellular IRF7-mediated innate immunity.