bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vesicular storage and secretion of l‐glutamate from glucagon‐like peptide 1‐secreting clonal intestinal L cells
Authors: Uehara Shunsuke , Jung Sun‐Kyung , Morimoto Riyo , Arioka Shigeo , Miyaji Takaaki , Juge Narinobu , Hiasa Miki , Shimizu Kahori , Ishimura Akinori , Otsuka Masato , Yamamoto Akitsugu , Maechler Pierre , Moriyama Yoshinori 
Published: December 2005

AbstractVesicular glutamate transporter (VGLUT) is responsible for the vesicular storage of l‐glutamate, and plays an essential role in glutamate‐mediated intercellular signal transmission in the CNS and in some neuroendocrine cells. Intestinal L cells are the glucose‐responsive neuroendocrine cells responsible for the secretion of glucagon‐like peptide 1 (GLP‐1). We have shown that intestinal L cells express VGLUT2, a VGLUT isoform, which suggests that L cells secrete l‐glutamate. In the present study, we investigated this possibility using GLUTag mouse clonal L cells. RT–PCR and northern blot analyses revealed expression of the VGLUT1 and VGLUT2 genes, but not of the VGLUT3 gene. Western blot analysis revealed immunological counterparts for VGLUT2, whereas an immunological counterpart of VGLUT1 was not detected. Indirect immunofluorescence microscopy revealed a punctate distribution of VGLUT2 immunoreactivity throughout the cells, which co‐localized with GLP‐1. Double‐labeling immunoelectronmicroscopy confirmed the association of VGLUT2 with GLP‐1‐containing secretory granules. The membrane fraction exhibited ATP‐dependent l‐glutamate uptake, which was sensitive to bafilomycin A1 (a vacuolar proton ATPase inhibitor) and Evans blue (a VGLUT inhibitor) but insensitive to d,l‐aspartate. Upon depolarization with KCl, GLUTag cells secreted appreciable amounts of l‐glutamate and GLP‐1. d‐Glucose and methyl‐α‐d‐glucopyranoside, stimulators of exocytosis of GLP‐1, also triggered the secretion of l‐glutamate. The l‐glutamate secretion was partially dependent on Ca2+ and sensitive to bafilomycin A1. These results demonstrated that GLUTag cells stored l‐glutamate in secretory granules and secreted it with GLP‐1 by exocytosis. As GLUTag cells and intestinal L cells express kainate receptors and plasma membrane glutamate transporters, these results support the concept of l‐glutamate‐mediated intercellular signaling in the vicinity of intestinal L cells.
Semaphorin 3A and neurotrophins: a balance between apoptosis and survival signaling in embryonic DRG neurons
Authors: Ben‐Zvi Ayal , Yagil Zohar , Hagalili Yamit , Klein Hagit , Lerman Omer , Behar Oded 
Published: December 2005

AbstractLarge numbers of neurons are eliminated by apoptosis during nervous system development. For instance, in the mouse dorsal root ganglion (DRG), the highest incidence of cell death occurs between embryonic days 12 and 14 (E12–E14). While the cause of cell death and its biological significance in the nervous system is not entirely understood, it is generally believed that limiting quantities of neurotrophins are responsible for neuronal death. Between E12 and E14, developing DRG neurons pass through tissues expressing high levels of axonal guidance molecules such as Semaphorin 3A (Sema3A) while navigating to their targets. Here, we demonstrate that Sema3A acts as a death‐inducing molecule in neurotrophin‐3 (NT‐3)‐, brain‐derived neurotrophic factor (BDNF)‐ and nerve growth factor (NGF)‐dependent E12 and E13 cultured DRG neurons. We show that Sema3A most probably induces cell death through activation of the c‐Jun N‐terminal kinase (JNK)/c‐Jun signaling pathway, and that this cell death is blocked by a moderate increase in NGF concentration. Interestingly, increasing concentrations of other neurotrophic factors, such as NT‐3 or BDNF, do not elicit similar effects. Our data suggest that the number of DRG neurons is determined by a fine balance between neurotrophins and Semaphorin 3A, and not only by neurotrophin levels.
Polyphenol amentoflavone affords neuroprotection against neonatal hypoxic‐ischemic brain damage via multiple mechanisms
Authors: Shin Dong Hoon , Bae Young Chul , Kim‐Han Jeong Sook , Lee Ji Hyun , Choi In Young , Son Kun Ho , Kang Sam Sik , Kim Won‐Ki , Han Byung Hee 
Published: December 2005

AbstractFlavonoids are naturally occurring polyphenolic compounds that have many biological properties, including antioxidative, anti‐inflammatory and neuroprotective effects. Here, we report that amentoflavone significantly reduced cell death induced by staurosporine, etoposide and sodium nitroprusside in neuroblastoma SH‐SY5Y cells. In post‐natal day 7 rats, hypoxic‐ischemic (H‐I) brain damage induced by unilateral carotid ligation and hypoxia resulted in distinct features of neuronal cell death including apoptosis and necrosis. In this model, a systemic administration of amentoflavone (30 mg/kg) markedly reduced the H‐I‐induced brain tissue loss with a wide therapeutic time window up to 6 h after the onset of hypoxia. Amentoflavone blocked the activation of caspase 3, characteristic of apoptosis, and the proteolytic cleavage of its substrates following H‐I injury. Amentoflavone also reduced the excitotoxic/necrotic cell death after H‐I injury in vivo and after oxygen/glucose deprivation in mouse mixed cultures in vitro. Treatment of mouse microglial cells with amentoflavone resulted in a significant decrease in the lipopolysaccharide‐induced production of nitric oxide and induction of inducible nitric oxide synthase and cyclo‐oxygenase‐2. Furthermore, amentoflavone decreased the inflammatory activation of microglia after H‐I injury when assessed by the microglial‐specific marker OX‐42. These data demonstrate for the first time that amentoflavone strongly protects the neonatal brain from H‐I injury by blocking multiple cellular events leading to brain damage.
Role of metalloproteinase‐dependent EGF receptor activation in α1‐adrenoceptor‐stimulated MAP kinase phosphorylation in GT1‐7 neurons
Authors: Shah Bukhtiar H. , Shah Farzana B. , Catt Kevin J. 
Published: December 2005

AbstractAdrenoceptors (ARs) are involved in the regulation of gonadotropin‐releasing hormone (GnRH) release from native and immortalized hypothalamic (GT1‐7) neurons. However, the AR‐mediated signaling mechanisms and their functional significance in these cells are not known. Stimulation of GT1‐7 cells with the α1‐AR agonist, phenylephrine (Phe), causes phosphorylation of extracellular signal‐regulated kinases 1 and 2 (ERK1/2) mitogen‐activated protein (MAP) kinases that is mediated by protein kinase C (PKC)‐dependent transactivation of the epidermal growth factor receptor (EGF‐R). Phe stimulation causes shedding of the soluble ligand, heparin‐binding EGF (HB‐EGF), as a consequence of matrix metalloproteinase (MMP) activation. Phe‐induced phosphorylation of the EGF‐R, and subsequently of Shc and ERK1/2, was attenuated by inhibition of MMP or HB‐EGF with the selective inhibitor, CRM197, or by a neutralizing antibody. In contrast, phosphorylation of the EGF‐R, Shc and ERK1/2 by EGF and HB‐EGF was independent of PKC and MMP activity. Moreover, inhibition of Src attenuated ERK1/2 responses by Phe, but not by HB‐EGF and EGF, indicating that Src acts upstream of the EGF‐R. Consistent with a potential role of reactive oxygen species (ROS), Phe‐induced phosphorylation of EGF‐R was attenuated by the antioxidant, N‐acetylcysteine. These data suggest that activation of the α1‐AR causes phosphorylation of ERK1/2 through activation of PKC, ROS and Src, and shedding of HB‐EGF, which binds to and activates the EGF‐R.
Erythropoietin protects against 6‐hydroxydopamine‐induced dopaminergic cell death
Authors: Signore Armando P. , Weng Zhongfang , Hastings Teresa , Van Laar Amber D. , Liang Qinghua , Lee Yong J. , Chen Jun 
Published: December 2005

AbstractParkinson's disease (PD) is a neurodegenerative disorder characterized by the death of midbrain dopaminergic neurons. In the present study, erythropoietin, a trophic factor that has both hematopoietic and neural protective characteristics, was investigated for its capacity to protect dopaminergic neurons in experimental Parkinson's disease. Using both the dopaminergic cell line, MN9D, and primary dopamine neurons, we show that erythropoietin (1–3 U/mL) is neuroprotective against the dopaminergic neurotoxin, 6‐hydroxydopamine. Protection was mediated by the erythropoietin receptor, as neutralizing anti‐erythropoietin receptor antibody abrogated the protection. Activation of Akt/protein kinase B (PKB), via the phosphoinositide 3‐kinase pathway, is a critical mechanism in erythropoietin‐induced protection, while activation of extracellular signal‐regulated kinase (ERK)1/2 contributes only moderately. Indeed, transfection of constitutively active Akt/PKB into dopaminergic cells was sufficient to protect against cell death. Furthermore, erythropoietin diminished markers of apoptosis in MN9D cells, including caspase 9 and caspase 3 activation and internucleosomal DNA fragmentation, suggesting that erythropoietin interferes with the apoptosis–execution process. When erythropoietin was administered to mice unilaterally lesioned with 6‐hydroxydopamine, it prevented the loss of nigral dopaminergic neurons and maintained striatal catecholamine levels for at least 8 weeks. Erythropoietin‐treated mice also had significantly reduced behavioral asymmetries. These studies suggest that erythropoietin can be an effective neuroprotective agent for dopaminergic neurons, and may be useful in reversing behavioral deficits associated with Parkinson's disease.
Predictive Validity of Measures of Comorbidity in Older Community Dwellers: The Insufficienza Cardiaca negli Anziani Residenti a Dicomano Study
Authors: Di Bari Mauro , Virgillo Adriana , Matteuzzi Daniela , Inzitari Marco , Mazzaglia Giampiero , Pozzi Claudia , Geppetti Pierangelo , Masotti Giulio , Marchionni Niccolò , Pini Riccardo 
Published: December 2005

OBJECTIVES: To compare the ability of five measures of comorbidity to predict mortality and incident disability in basic activities of daily living (BADLs) in unselected older persons.DESIGN: An assessment of the data obtained from the Insufficienza Cardiaca negli Anziani Residenti a Dicomano (ICARe Dicomano) Study, a longitudinal epidemiological survey on heart failure in older people.SETTING: Dicomano, a small, rural town near Florence, Italy.PARTICIPANTS: The entire population aged 65 and older living in Dicomano, Italy, was enrolled in the ICARe Dicomano Study.MEASUREMENTS: At baseline (1995), comorbidity was quantified in 688 participants, based on clinical diagnoses, using disease count (DC), Charlson Comorbidity Index (CCI), Index of Co‐Existent Diseases (ICED), and Geriatric Index of Comorbidity (GIC), or on drug use, using Chronic Disease Score (CDS). Incident ADL disability was assessed in 1999 and vital status in 2004.RESULTS: Mortality increased with the severity of comorbidity, with hazard ratios around 2 when comparing the highest and the lowest quartiles of DC, CCI, and ICED in Cox regressions adjusted for age, sex, and physical and cognitive performance. Prediction of mortality with GIC and CDS was only borderline significant. All measures predicted incident ADL disability; the strongest risk gradient (hazard ratio=8.2 between the highest and lowest quartiles) was observed with ICED. Physical and, to a minor extent, cognitive performance added significantly to predicting mortality and incident BADL disability.CONCLUSION: All the measures of comorbidity predicted death and BADL disability in older community dwellers. DC, CCI, and ICED performed better than GIC and CDS. Physical performance measures are strong, independent contributors to the prediction of these outcomes.
Morbidity and Older Persons' Perceptions of the Quality of Their Primary Care
Authors: Shadmi Efrat , Boyd Cynthia M. , Hsiao Chun‐Ju , Sylvia Martha , Schuster Alyson B. , Boult Chad 
Published: December 2005

OBJECTIVES: To quantify the association between community‐dwelling older persons' level of morbidity and their perceptions of the quality of their primary care.DESIGN: Cross‐sectional study.SETTING: Urban primary care practice.PARTICIPANTS: A sample of community‐dwelling members of a capitated health plan aged 65 and older who were patients of four general internists in one urban practice (N=120).MEASUREMENTS: The Johns Hopkins Adjusted Clinical Groups case‐mix system was used to designate a person's aggregate morbidity level as moderate or high depending on the number and types of chronic conditions they had. Aspects of quality of primary care (physician–patient communication, interpersonal treatment, knowledge of patient, integration of care, and trust in physician) were assessed using the Primary Care Assessment Survey.RESULTS: All participants were classified as having moderate (41%) or high morbidity (59%). Older adults with high morbidity assigned a lower rating to all aspects of quality of primary care (physician–patient communication (P=.001), interpersonal treatment (P=.002), knowledge of patient (P=.03), integration of care (P=.004), and trust in physician (P=.01)) than those with moderate morbidity. The differences in quality of primary care remained statistically significant after controlling for age, sex, race, and education level.CONCLUSION: Older persons with multiple chronic conditions report inadequate quality of primary care and dissatisfaction with their care. Those with high morbidity levels experience poorer quality of primary care than those with moderate morbidity in all five aspects measured here.
Loss of molars in periodontally treated patients: a retrospective analysis five years or more after active periodontal treatment
Authors: Dannewitz Bettina , Krieger Jörg K. , Hüsing Johannes , Eickholz Peter 
Published: December 2005

AbstractObjectives: Evaluation of tooth loss in molars and prognostic factors for molar survival.Material and Methods: Five hundred and five molars in 71 patients (mean age 46 years; 40 females) were evaluated. The following inclusion criteria were required: periodontal therapy of at least one molar, at least 5 years of supportive periodontal therapy, and baseline assessment of furcation involvement (FI).Results: At baseline 200 of 505 molars exhibited no FI, 116 degree I, 122 degree II, and 67 degree III FI. Twenty‐seven molars did not receive periodontal treatment; 127 molars were subjected to non‐surgical therapy, and 227 to flap surgery. Tunnel preparation was performed on 14 molars, root resection on 20, regenerative therapy on 57 teeth, and 33 molars were extracted. During the average follow‐up period of 107 months 38 molars were lost additionally. Molars with degree III FI had the highest mortality. A multi‐level proportional hazard model revealed smoking, baseline bone loss, number of molars left, and degree III FI as risk factors influencing the retention time of molars.Conclusion: Overall periodontal therapy results in a good prognosis of molars. Degree III FI leads to a significant deterioration of prognosis. Beyond FI smoking, baseline bone loss, and number of molars left influence molar survival.
Immediate effect of instrumentation on the subgingival microflora in deep inflamed pockets under strict plaque control
Authors: Rhemrev G. E. , Timmerman M. F. , Veldkamp I. , Van Winkelhoff A. J. , Van der Velden U. 
Published: December 2005

AbstractObjective: To investigate (1) reduction in the number of microorganisms obtained directly after subgingival instrumentation, (2) rate of bacterial re‐colonization during 2 weeks, under supragingival plaque‐free conditions.Materials and Methods: Effects of subgingival instrumentation were measured at one deep pocket in 22 patients (11 smokers and 11 non‐smokers). Immediately after initial therapy, experimental sites, under strict plaque control, were instrumented subgingivally. Microbiological evaluation was performed at pre‐instrumentation, immediate post‐instrumentation and 1 and 2 weeks post‐instrumentation.Results: Mean total anaerobic clolony forming units (CFUs) dropped from 3.9 × 106 before to 0.09 × 106 immediately following instrumentation. Significant reductions were found for Tannerella forsythia, Micromonas micros, Fusobacterium nucleatum and spirochetes. Significant reductions were not observed for Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Campylobacter rectus. Except for spirochetes, no reduction in prevalence of specific periodontal bacteria was found immediately after instrumentation. During follow‐up, mean total CFU tended to increase. Prevalence of periodontal bacteria further reduced. No effect of smoking was found.Conclusion: Results indicate that subgingival mechanical cleaning in itself, has a limited effect, in actually removing bacteria. The subsequent reduction in prevalence of specific periodontal bacteria shows that it is apparently difficult for these species to survive in treated pockets.
Modern Imaging of Brain Malformations with Particular Reference to Endocrinology
Authors: Griffiths P. D. 
Published: December 2005

SummaryAdvances in neuro‐imaging techniques, such as MR imaging, have allowed the demonstration of a wide range of subtle pathologies not possible with previous methods. This is particularly true in the case of brain malformations. In this review I will discuss the range of imaging methods available and describe a structural approach to classifying the range of brain malformations. The most common variety of pituitary malformations are also included in this review.
Radiative transfer along rays in curved space–times
Authors: Broderick Avery E. 
Published: December 2005

Abstract
Radiative transfer in curved space–times has become increasingly important to understanding high-energy astrophysical phenomena and testing general relativity in the strong field limit. The equations of radiative transfer are physically equivalent to the Boltzmann equation, where the latter has the virtue of being covariant. We show that by a judicious choice of the basis of the phase space, it is generally possible to make the momentum derivatives in the Boltzmann equation vanish along an arbitrary (including non-geodesic) path, thus reducing the problem of radiative transfer along a ray to a path integral in coordinate space.
A Simple Solution for Drawdown Calculation in a Large‐Diameter Well
Authors: Çogo;imen Mesut 
Published: December 2005

AbstractLarge‐diameter wells are used extensively in developing countries, especially in unconsolidated alluvial deposits or fissured rocks of shallow depths. Principally, they have large storage volume ready for exploitation by direct pumping. A simple calculation procedure for drawdown in a large‐diameter wellhas been proposed. This is a new method that involves the use of the independent variable transform. The governing equation can be used easily for the evaluation of drawdowns in both pumping and observation wells. Type curves obtained by the procedure developed in this paper are compared with those already available in ground water literature. The accordance of the derived type curves in this study with that of Papadopulos and Cooper (1967) is obvious. However, in this paper, a simple transient solution is presented that allows one to find the drawdown at the pumping and observation wells in an extensive confined aquifer.
Use of Quantitative Models to Design Microbial Transport Experiments in a Sandy Aquifer
Authors: Scheibe Timothy D. , Chien Yi‐Ju , Radtke Jonathan S. 
Published: December 2005

AbstractA suite of numerical models was applied to the problem of designing field tracer and bacterial injection experiments in a sandy surficial aquifer near Oyster, Virginia. The models were constructed based on the integration of diverse characterization data including hydrologic, geophysical, geological, geochemical, and biological information. A one‐dimensional particle‐tracking model was used to analyze laboratory transport experiments conducted using intact core samples to prescribe transport parameters describing solute dispersion and bacterial fate. A geostatistical model of three‐dimensional hydraulic conductivity variations was developed, conditioned on in situ measurements of hydraulic conductivity and interpretations of geophysical data, and used to generate alternative aquifer descriptions. A regional‐scale, two‐dimensional flow model was used to design pumping rates of a forced‐gradient hydraulic control system. Information from these various models was then combined into a high‐resolution, three‐dimensional flow and transport model for the prediction of field‐scale solute and bacterial transport. Model predictions were used in an iterative experimental design process to specify. (1) the locations of multilevel samplers for monitoring transport; (2) frequency and timing of sample collection during bromide tracer injection experiments; and (3) frequency and timing of sample collection during a bacterial injection experiment. At each stage of the design, information gained during the previous stage was used to refine the model and target subsequent experimentation.
Noninvasive Determination of the Location and Distribution of DNAPL Using Advanced Seismic Relfection Techniques
Authors: Temples Tom J. , Waddell Michael G. , Domoracki William J. , Eyer Jerome 
Published: December 2005

AbstractRecent advances in seismic reflection amplitude analysis (e.g., amplitude versus offset‐AVO, bright spot mapping) technology to directly detect the presence of subsurface DNAPL (e.g., CCl4) were applied to 216–Z‐9 crib, 200 West Area, DOE Hanford Site, Washington.Modeling to determine what type of anomaly might be present was performed. Model results were incorporated in the interpretation of the seismic data to determine the location of any seismic amplitude anomalies associated with the presence of high concentrations of CCl4. Seismic reflection profiles were collected and analyzed for the presence of DNAPL. Structure contour maps of the contact between the Hanford fine unit and the Plio/Pleistocene unit and between the Plio/Pleistocene unit and the caliche layer were interpreted to determine potential DNAPL flow direction.Models indicate that the contact between the Plio/Pleistocene unit and the caliche should have a positive reflection coefficient. When high concentrations of CCl4 are present, the reflection coefficient of this interface displays a noticeable positive increase in the seismic amplitude (i.e., bright spot).Amplitude data contoured on the Plio/Pleistocene‐caliche boundary display high values indicating the presence of DNAPL to the north and east of the crib area. The seismic data agree well with the well control in areas of high concentrations of CCl4.
Numerical Inverse Interpretation of Single‐Hole Pneumatic Tests in Unsaturated Fractured Tuff
Authors: Vesselinov Velimir V. , Neuman Shlomo P. 
Published: December 2005

AbstractA numerical inverse method was used to interpret simultaneously multirate injection and recovery data from single‐hole pneumatic tests in unsaturated fractured tuff at the Apache Leap Research Site near Superior, Arizona. Our model represents faithfully the three‐dimensional geometry of boreholes at the site, and accounts directly for their storage and conductance properties by treating them as high‐permeability and high‐porosity cylinders of finite length and radius. It solves the airflow equations in their original nonlinear form and yields information about air permeability, air‐filled porosity and dimensionless borehole storage coefficient. Some of this is difficult to accomplish with analytical type‐curves. Air permeability values obtained by our inverse method agree well with those obtained by steady‐state and type‐curve analyses.