bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole‐brain glutamate metabolism evaluated by steady‐state kinetics using a double‐isotope procedure: effects of gabapentin
Authors: Xu Y. , Öz G. , LaNoue K. F. , Keiger C. J. , Berkich D. A. , Gruetter R. , Hutson S. H. 
Published: August 2004

AbstractCerebral rates of anaplerosis are known to be significant, yet the rates measured in vivo have been debated. In order to track glutamate metabolism in brain glutamatergic neurons and brain glia, for the first time unrestrained awake rats were continuously infused with a combination of H14CO3– and [1−13C]glucose in over 50 infusions ranging from 5 to 60 min. In whole‐brain extracts from these animals, the appearance of 14C in brain glutamate and glutamine and appearance of 13C in the C‐4 position of glutamate and glutamine were measured as a function of time. The rate of total neuronal glutamate turnover, the anaplerotic rate of synthesis of glutamine and glutamate from H14CO3–, flux through the glutamate/glutamine cycle, and a minimum estimate of whole‐brain anaplerosis was obtained. The rate of synthesis of 14C‐glutamate from H14CO3– was 1.29 ± 0.11 nmoles/min/mg protein, whereas the rate of synthesis of 14C‐glutamine was 1.48 ± 0.10 nmoles/min/mg protein compared to total glutamate turnover of 9.39 ± 0.73 nmoles/min/mg protein. From the turnover rate of glutamine, an upper limit for flux through the glutamate/glutamine cycle was estimated at 4.6 nmoles/min/mg protein. Synthesis of glutamine from H14CO3– was substantial, amounting to 32% of the glutamate/glutamine cycle. These rates were not significantly affected by a single injection of 100 mg/kg of the antiepileptic drug gabapentin. In contrast, acute administration of gabapentin significantly lowered incorporation of H14CO3– into glutamate and glutamine in excised rat retinas, suggesting metabolic effects of gabapentin may require chronic treatment and/or are restricted to brain areas enriched in target enzymes such as the cytosolic branched chain aminotransferase. We conclude that the brain has a high anaplerotic activity and that the combination of two tracers with different precursors affords unique insights into the compartmentation of cerebral metabolism.
Quantitative Analytical Methods in Translation Research
Authors: Dawson Jeffrey D. 
Published: August 2004

ABSTRACTIn research involving quality of health care, an intervention is often attempted at one or more institutions. This article presents the advantages and disadvantages of various study designs that might be considered for such institution‐based research, looking at the issues of comparison groups, replication, blocking, and contamination. Three examples illustrate the importance of accommodating the lack of independence or clustering that occurs among subjects within an institution, and show how these accommodations for clustering can sometimes be made by applying basic statistical techniques to institution‐level outcomes, whereas at other times more sophisticated approaches are necessary.
Improving Care to Patients with Ischemic Heart Disease: Experiences in a Single Network of the Veterans Health Administration
Authors: Pineros Sandra L. , Sales Anne E. , Li Yu‐Fang , Sharp Nancy D. 
Published: August 2004

ABSTRACT Background: Ischemic heart disease (IHD) is the leading cause of death in the United States. Lowering serum cholesterol levels reduces coronary events and mortality; this effect is most evident in patients with preexisting IHD. Aims: The primary aim of this article is to describe a set of interventions that were piloted in a single, regional Veterans Integrated Service Network (VISN) to promote secondary prevention among patients with IHD and to explore the effect of those interventions on patient outcomes. Methods: An observational, before‐and‐after study of clinical interventions to improve lipid guideline compliance in VISN 20 (the Veterans Administration Northwest Network) was conducted. A total of 2,467 patients with established coronary artery disease from three medical facilities in VISN 20 were included. Each medical facility chose different interventions to lower low‐density lipoprotein cholesterol (LDL‐c) levels in their patients. One facility chose a paper point‐of‐care reminder, a second chose a lipid clinic, and a third chose audit/feedback to clinicians in addition to a patient‐education component. Data came from a relational database that mirrors the clinical information system at each site. Outcomes included the proportion of patients who had their LDL‐c measured, the proportion of patients who had lipid‐lowering agents prescribed, and the proportion of patients at LDL‐c goal of lower than 100 mg/dL measured before, during, and after the intervention period. Results: Statistically significant improvements were observed within sites after the interventions were implemented. Implications for Practice: Interventions that focused on secondary prevention in this high‐risk group were moderately successful in changing practice. Tailoring interventions to the needs of a specific site of care is feasible and may add to the likelihood of succeeding. Conclusion: Overall, the three facilities improved in lipid measurement and management for patients with coronary artery disease.
Advancing Quality of Urinary Incontinence Evaluation and Treatment in Nursing Homes Through Translational Research
Authors: Watson Nancy M. 
Published: August 2004

ABSTRACT Aim: This article presents the development of ongoing research to improve the evaluation and treatment of urinary incontinence (UI) in nursing homes through “A Model for Use of the Urinary Incontinence Guideline in US Nursing Homes” under the initiative Translating Research into Practice (TRIP II). Background: The previous research provided the definition of the clinical practices needing improvement, the relative size of the population needing care, and an estimate of the manpower required. The model proposed nurse practitioners (NPs) as consultants to nursing homes to perform the basic incontinence evaluation and treatment, thereby (1) improving incontinence evaluation and treatment, (2) reducing UI, (3) reducing complications, and (4) increasing cost savings attributable to UI. Approach: A quasi‐experimental research design with pre‐ and post‐comparison was selected utilizing four control and four experimental NP caseloads followed for 16 weeks post‐onset (n = 320). Findings: Findings are not yet available from this study, which is ongoing. Discussion: The real‐world challenges presented by this translational research and their solutions are discussed.
Translation Research: Where Do We Go from Here?
Authors: Fraser Irene 
Published: August 2004

ABSTRACT Aim: Where do we go from here? This article draws on other articles in this supplement, the dialogue from the meeting that generated it, and other sources to identify steps to advance translation research, and in particular to achieve broader translation and use of evidence. Implications: To move from the growing accumulation of individual successes in translation to broader scale translation and implementation of evidence, those who use research and those who do research will need to do four things: (1) increase synergy and synchronization across studies, through cross‐disease studies, adoption of a common and precise language to describe interventions, addressing issues of customization of interventions, and finding commonality in quality and outcomes measures; (2) take account of organizational factors that can shape the impact of interventions, and also move to the implementation of organizational evidence; (3) address environmental factors such as reimbursement and market competition; and (4) take findings to a larger scale through national demonstrations, efforts of national agents of change, challenge or partnership grants, or use of provider‐based networks.
An Artificial Myocardium Assist System: Electrohydraulic Ventricular Actuation Improves Myocardial Tissue Perfusion in Goats
Authors: Wang Qingtian , Yambe Tomoyuki , Shiraishi Yasuyuki , Duan Xudong , Nitta Shinichi , Tabayashi Kouichi , Umezu Mitsuo 
Published: August 2004

Abstract:  Artificial hearts and ventricular assist devices have been widely used clinically to assist patients with severe heart failure. Unfortunately, direct contact between the device and the patient's blood leads to thromboembolic events, and then the need for anticoagulation and infections contribute significantly to complication and mortality. Compressing the dysfunctional heart from its epicardial surface, a nonblood‐contacting method of direct mechanical ventricular actuation could provide ventricular support, pulsatile blood flow, and avoid interactions between blood and the surface of the artificial assistance system. An ElectroHydraulic Artificial Myocardial (EHAM) assist system that might assist heart muscle contraction has been developed. The purpose of this study is to determine the efficiency of the EHAM system in perfusing myocardial tissue in an acute animal experiment.Method:  Healthy adult goats (n = 8) were used in acute animal experiments. A left lateral thoracotomy was done and the chest was opened through the 4th and 5th rib resection. Hemodynamic parameters were continuously monitored including ECG, aortic blood pressure, left ventricular pressure, and pulmonary artery pressure. Myocardial tissue perfusion was measured by using an Omega flow laser fiber attached on the surface of the heart.Results:  All the animals achieved significantly increased blood pressure, pulmonary artery flow, and myocardial tissue perfusion during the EHAM compression compared with the nondriving (pre‐assisted) mode.Conclusions:  The EHAM system can effectively improve myocardial tissue perfusion and increase blood pressure thus demonstrating a potential for treating failing cardiac performance.
Matrix metalloproteinase‐1 and tissue inhibitor of metalloproteinase‐1 production in human gingival fibroblasts: the role of protein kinase C
Authors: Domeij H. , Modéer T. , Yucel‐Lindberg T. 
Published: August 2004

Background:  Matrix metalloproteinase‐1 (MMP‐1) plays an important role in tissue remodelling and in the pathology of inflammatory diseases including periodontitis. The activity of MMP‐1 is firmly controlled by the endogenous tissue inhibitor of metalloproteinase‐1 (TIMP‐1).Objective:  The aim of the study was to investigate the production and regulation of MMP‐1 and TIMP‐1 with special regards to the enzyme protein kinase C (PKC) in human gingival fibroblasts.Methods:  Gingival fibroblasts were treated with substances related to PKC such as phorbol 12‐myristate 13‐acetate (PMA), interleukin‐1β, Ca2+‐ionophore A231817 and inhibitors of PKC, p38 mitogen‐activated protein kinase (p38 MAPK) and tyrosine kinase.Results:  The PKC activator PMA stimulated the production of MMP‐1 and TIMP‐1 at both the transcriptional and the translational level. The production of MMP‐1 and TIMP‐1 stimulated by PMA was abolished by the PKC inhibitor bisindolylmaleimide. Treatment of the cells with interleukin‐1β or A23187 synergistically increased the stimulatory effect of PMA on MMP‐1 production. In contrast, TIMP‐1 production was unaffected by interleukin‐1β and reduced by A23187. Tyrosine kinase inhibitor herbimycin A reduced MMP‐1 production induced by PMA, whereas the p38 MAPK‐inhibitor SB 203580 synergistically increased the stimulatory effect of PMA on both MMP‐1 and TIMP‐1 production.Conclusion:  The present study shows that MMP‐1 and TIMP‐1 production is regulated differently by interleukin‐1β and calcium in human gingival fibroblasts and that this difference is markedly amplified in the presence of the PKC‐activator PMA. Taken together, the discrepancy in the production of MMP‐1 and TIMP‐1 in gingival fibroblasts may contribute to tissue destruction in periodontal diseases.
γ‐Interferon enhances expression of CD14/MyD88 and subsequent responsiveness to lipopolysaccharide from Actinobacillus actinomycetemcomitans in human gingival fibroblasts
Authors: Mochizuki S. , Kobayashi M. , Suzuki T. , Oikawa A. , Koseki T. , Nishihara T. , Hasegawa K. 
Published: August 2004

Objectives:  CD14, toll‐like receptor 4 (TLR4) and MyD88 have been shown to mediate responsiveness in host cells to lipopolysaccharide. We investigated here the regulatory effects of inflammatory cytokines on the expression of membrane CD14 (mCD14), TLR4 and MyD88, and on subsequent responsiveness to lipopolysaccharide from Actinobacillus actinomycetemcomitans in human gingival fibroblasts.Materials and methods:  Following treatment with either interleukin‐1β, tumor necrosis factor‐α (TNF‐α) or γ‐interferon (IFN‐γ), expression of mCD14/TLR4 and MyD88 was determined by flow cytometry and western blotting, respectively. After pretreatment with IFN‐γ, cells were pre‐incubated with either anti‐CD14 antibody MY4 or anti‐TLR4 antibody HTA125 and subsequently treated with A. actinomycetemcomitans lipopolysaccharide. Then, phosphorylation of mitogen‐activated protein (MAP) kinases and IκBα was examined by western blotting, and production of interleukin‐6 and interleukin‐8 was measured by their respective enzyme‐linked immunosorbent assay (ELISA) kits.Results:  IFN‐γ stimulated expression of mCD14, whereas ‐1β and TNF‐α did not. Expression of MyD88 but not TLR4 was also enhanced by IFN‐γ. The lipopolysaccharide activated MAP kinases, such as extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK) and p38, and IκBα and stimulated production of interleukin‐6 and interleukin‐8. The lipopolysaccharide‐stimulated interleukin‐6 and interleukin‐8 production was markedly inhibited by MY4 or HTA125. Pretreatment with IFN‐γ augmented the following activation of MAP kinases and IκBα and production of interleukin‐6 and interleukin‐8 in response to the lipopolysaccharide.Conclusions:  These results suggest that the augmentation by IFN‐γ of the responsiveness to A. actinomycetemcomitans lipopolysaccharide, such as activation of MAP kinases and IκBα and terminal cytokine production in human gingival fibroblasts, may be partially mediated by up‐regulation of CD14 and MyD88 expression.
Critical steps in electronic volume quantification of gingival crevicular fluid: the potential impact of evaporation, fluid retention, local conditions and repeated measurements
Authors: Tözüm Tolga F. , Hatipoğlu Hasan , Yamalik Nermin , Gürsel Mihtikar , Alptekin Nilgün Ö. , Ataoğlu Tamer , Marakoğlu Ismail , Gürsoy Ulvi K. , Eratalay Kenan 
Published: August 2004

Background and objectives:  Various methodological factors may operate during clinical gingival crevicular fluid (GCF) sampling, volume quantification or subsequent laboratory analysis. For precise volume quantification, specific concern for generation and maintenance of a reliable calibration curve, the potential risk of GCF loss as a result of evaporation or fluid retention on actual volume and the impact of local conditions is needed because each of these factors may act as a source of subsequent volumetric distortions. Thus, the present study aimed to analyse the impact of sample transfer time on the rate of evaporation and the possibility of fluid retention, and the impact of local conditions and number of replicated measurements on the reliability of calibration data.Materials and methods:  To analyse evaporative errors, standardized Periopaper® strips provided with known test volumes (0.1 µl, 0.2 µl, 0.5 µl and 0.6 µl) were transferred to Periotron 8000® with different time intervals (immediately, 5 s, 30 s and 60 s). For fluid retention, after quantifying the actual volume of the strips provided with known volumes (0.1 µl and 0.6 µl) of two test fluids, a second set of measurements was performed using dry strips. To determine the impact of local conditions (temperature and humidity) and the validity of 3, 5 and 20 replications (0.0–0.6 µl with 0.1‐µl increments) on device calibration for 20°C and 25°C, electronic readings were obtained from three devices at three different locations. Differences in volumetric data in each experimental design were statistically analysed.Results:  No significant fluid loss was observed within 5 s, but evaporation clearly led to volumetric distortions with extending transfer times (30 s or 60 s) (p < 0.05). Measurable amounts of fluid retention were found for both volumes and both test fluids, but not with identical patterns. Local conditions resulted in unique calibration data for each test volume and for each device. Although a 5°C increase generally provided higher readings, this was not observed for all devices at all volumes. Additional replicates (n = 5 or n = 20) did not seem to add any further reliability to the triplicate scores for the given test volumes.Conclusion:  The findings of the present study confirm the reliability of triplicate readings, and uniqueness of each device and electronic data and the distinct impact of local environmental conditions on the generation/maintenance of calibration scores for each particular device. Furthermore, they underline time‐dependent evaporation and fluid retention as additional technical concerns and once again highlight the importance of methodological standardization of the electronic volume quantification process.
Streptococcus pneumoniae-Induced Caspase 6-Dependent Apoptosis in Lung Epithelium
Authors: Schmeck Bernd , Gross Ralph , N′Guessan Phillipe Dje , Hocke Andreas C. , Hammerschmidt Sven , Mitchell Tim J. , Rosseau Simone , Suttorp Norbert , Hippenstiel Stefan 
Published: August 2004

ABSTRACTStreptococcus pneumoniaeis the major pathogen of community-acquired pneumonia and one of the most common causes of death due to infectious diseases in industrialized countries. Lung epithelium lines the airways and constitutes the first line of innate defense against respiratory pathogens. Little is known about the molecular interaction of pneumococci with lung epithelial cells. Apoptosis of lung epithelium is involved in some bacterial lung infections. In this study different pneumococcal strains specifically induced either apoptotic or necrotic death of human alveolar and bronchial epithelial cells. Pneumococcus-induced apoptosis did not depend on the virulence factors pneumolysin and H2O2. Apoptotic cells showed increased activity of caspases 6, 8, and 9 but not increased activity of caspase 3. Moreover, programmed cell death could be strongly reduced by a caspase 6 inhibitor and a pan-caspase inhibitor. Inhibitors of calpain and chymotrypsin- and trypsin-like proteases also reduced pneumococcus-induced apoptosis. Furthermore, pneumococcus-infected human alveolar epithelial cells showed Bid cleavage and reduced levels of Bcl2 and Bax. Overexpression of Bcl2 in these cells reduced apoptosis significantly. Thus, pneumococci induced apoptosis of human alveolar and bronchial epithelial cells. Programmed cell death was executed by caspase 6 and noncaspase proteases, but not by caspase 3, and could be blocked by overexpression of Bcl2.
Global Cell Surface Conformational Shift Mediated by a
Candida albicans
Adhesin
Authors: Rauceo Jason M. , Gaur Nand K. , Lee Kyeng-Gea , Edwards John E. , Klotz Stephen A. , Lipke Peter N. 
Published: August 2004

ABSTRACT

Candida albicans
maintains both commensal and pathogenic states in humans. Both states are dependent on cell surface-expressed adhesins, including those of the Als family. Heterologous expression of Als5p at the surface of
Saccharomyces cerevisiae
results in Als5p-mediated adhesion to various ligands, followed by formation of multicellular aggregates. Following adhesion of one region of the cell to fibronectin-coated beads, the entire surface of the cells became competent to mediate cell-cell aggregation. Aggregates formed in the presence of metabolic inhibitors or signal transduction inhibitors but were reduced in the presence of 8-anilino-1-naphthalene-sulfonic acid (ANS) or Congo Red (CR), perturbants that inhibit protein structural transitions. These perturbants also inhibited aggregation of
C. albicans
. An increase in ANS fluorescence, which accompanied Als-dependent cellular adhesion, indicated an increase in cell surface hydrophobicity. In addition,
C. albicans
and Als5p-expressing
S. cerevisiae
showed an aggregation-induced birefringence indicative of order on the cell surface. The increase in birefringence did not occur in the presence of the aggregation disruptants ANS and CR. These results suggest a model for Als5p-mediated aggregation in which an adhesion-triggered change in the conformation of Als5p propagates around the cell surface, forming ordered aggregation-competent regions.
Treatment of Mice with the Neutrophil-Depleting Antibody RB6-8C5 Results in Early Development of Experimental Lyme Arthritis via the Recruitment of Gr-1−Polymorphonuclear Leukocyte-Like Cells
Authors: Brown Charles R. , Blaho Victoria A. , Loiacono Christie M. 
Published: August 2004

ABSTRACTRecently, we demonstrated that blocking the entry of neutrophils intoBorrelia burgdorferi-infected joints in mice deficient in the chemokine receptor CXCR2 prevented the development of experimental Lyme arthritis. Neutrophils were marginalized in blood vessels at the site of infection but could not enter the joint tissue. In the present study, we treated both genetically arthritis-resistant DBA/2J (DBA) and arthritis-susceptible C3H/HeJ (C3H) mice with the neutrophil-depleting monoclonal antibody RB6-8C5 (RB6) to determine the effect on arthritis development. Surprisingly, both DBA and C3H mice treated with RB6 developed arthritis at 1 week postinfection, approximately 1 week earlier than the control-treated C3H mice. The early development of arthritis in the RB6-treated mice was accompanied by an influx into the joints of cells with ring-shaped polymorphonuclear leukocyte (PMN) cell morphology that were negative for the Gr-1 neutrophil maturation marker. RB6 treatment of mice also resulted in increased numbers ofB. burgdorfericells in the joints at 7 days postinfection and earlier expression of the chemokines KC and monocyte chemoattractant protein 1 in the joints compared to control-treated animals. Together, these results suggest that recruitment of neutrophils or PMN-like cells into an infected joint is a key requirement for Lyme arthritis development and that altered recruitment of these cells into the joints of arthritis-resistant mice can exacerbate the development of pathology.
CD4+T Cells in the Pathogenesis of Murine Ocular Toxoplasmosis
Authors: Lu Fangli , Huang Shiguang , Kasper Lloyd H. 
Published: August 2004

ABSTRACTThe role of CD4+T cells in the pathogenesis of ocular toxoplasmosis was investigated in murine models utilizing inbred C57BL/6 mice deficient either in CD4+, CD8+, or B cells (μMT). Severe necrosis and inflammation with replicating parasites were observed in the eyes of control mice after primary ocular infection, and near-normal histology with few tachyzoites was observed in the eyes of mice immunized intraperitoneally with the avirulent ts-4 strain followed by intraocular challenge with the RH strain ofToxoplasma gondii. In contrast, mild inflammation without evidence of necrosis associated with increased parasite burdens were observed in the eyes of CD4 knockout (KO) mice after both primary ocular infection and challenge with RH tachyzoites. CD8 KO mice, as well as μMT mice, demonstrated increased ocular necrosis in response to either primary ocular infection or challenge. The parasite burden was increased in the eyes of both CD8 KO and μMT mice in which the parasite load was even higher. As expected, there were no increases in the levels of immunoglobulin G in serum or aqueous humor in μMT mice, and there was no increase in the levels of gamma interferon and tumor necrosis factor alpha in the sera of CD4 KO mice after both infection and challenge. These results suggest that the ocular inflammatory response to the parasite is mediated primarily by the CD4+-T-cell response. CD8+T cells and B cells may play an important role in limiting tachyzoite proliferation in the eyes. Mice deficient in CD8+CD4+T cells or B cells exhibit diminished vaccine-induced resistance and increased ocular parasite burden after challenge.