bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of insulin production by cyproheptadine in RINm5F rat insulinoma cells
Authors: Miller C. P. , Reape T. J. , Fischer L. J. 
Published: October 2006

AbstractThe clonal insulin producing cell line RINmSF was evaluated as a model for the action of cyproheptadine (CPH)‐like diabetogenic com pounds in the rat pancreas. Treatment with 10 μM CPH and selected structural analogs under culture conditions produced a progressive loss of cellular insulin which reached 30% of control within 24 hours. Comparison of the activities of the analogs 4‐diphenylmethylpiperidine (4‐DPMP) and 2‐di‐phenylmethylpiperidine (2‐DFMP) to produce cellular insulin depletion showed that 4‐DPMP was as active as CPH but 2‐DPMP had no activity at the highest concentration employed (10 μM). The CPH metabolite desmethyl CPH‐epoxide was five times more active than the parent compound in producing loss of insulin in RINm5F cells. These results are consistent with previously published results of CPH actions in vivo. An inhibition of insulin biosynthesis with no loss of preproinsulin mRNA occurred in RINm5F cells treated with CPH or DMCPH‐epoxide. This suggests that an effect on transcription may not be the primary action by which CPH and its analogs inhibit insulin synthesis in vivo.
Effects of P450 inhibition and induction on the olfactory toxicity of β, β′‐iminodipropionitrile (IDPN) in the rat
Authors: Genter M. B. , Deamer N. J. , Cao Y. , Levi P. E. 
Published: October 2006

AbstractIn addition to the neurotoxic effects of β, β′‐iminodipropionitrile (IDPN) which have been previously reported by other investigators, the olfactory toxicity of this compound has recently been uncovered in this laboratory. Due to the apparently conflicting observations that the IDPN‐induced lesion in the olfactory mucosa is very focal in nature (suggesting site‐specific activation) and the observation by other investigators that the behavioral effects of IDPN appear to be due to the parent compound, we initiated studies into the possible role of the cytochrome P450 enzymes in the olfactory toxicity of IDPN. Immunohistochemical studies with antibodies raised against several different P450 isoforms revealed good correlation between IDPN‐induced olfactory mucosal degeneration and the localization of a protein immunoreacting with an antibody to P450 2E1. Enzymatic studies revealed that there is approximately fivefold more ρ‐nitrophenol hydroxylation activity in the olfactory mucosa than in the liver on a per milligram microsomal protein basis. Administration of 1% acetone in the drinking water increased the levels of olfactory mucosal 2E1, and the increase in enzyme levels corresponded to increased olfactory toxicity of IDPN; inhibition of P450 activities with either metyrapone or carbon tetrachloride eliminated or significantly decreased the olfactory toxicity of IDPN, respectively. These studies suggest a role for cytochrome P450, specifically the 2E1 isoform, in the activation of IDPN within the nasal mucosa.
Biphasic modulation of protein kinase C (PKC) activity by polychlorinated dibenzo‐p‐dioxins (PCDDs) in serum‐deprived rat aortic smooth muscle cells
Authors: Weber Thomas J. , Ou Xiaolan , Merchant Mark , Wang Xiaohong , Safe Stephen H. , Ramos Kenneth S. 
Published: October 2006

AbstractPrevious studies in this laboratory have shown that benzo(a)pyrene (BaP) modulates protein kinase C (PKC)‐mediated phosphorylation of aortic smooth muscle cell (SMC) proteins. This observation is consistent with the ability of other aromatic hydrocarbons (AHs), such as 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), to modulate kinase activities in cells of hepatic, testicular, and thymic origin. Because all these chemicals share the ability to bind the aryl hydrocarbon receptor (AhR), the present studies were conducted to determine if changes in PKC activity by AHs conform with established structure‐activity relationships. Experiments were conducted to examine the effects of TCDD, 2,3,7,8‐tetrachlorodibenzofuran (TCDF), and 2,8‐dichlorodibenzodioxin (DCDD) on the phosphorylation of exogenous histone type‐III under basal and PKC‐activating conditions. These congeners exhibit both high (TCDD and TCDF) and low (DCDD) AhR agonist activities. Measurements of kinase activity were conducted in the cytosolic and particulate fractions of growth‐arrested (i.e., serum‐deprived) cultured rat aortic SMCs incubated with 10 nM TCDD, TCDF, and DCDD for 0.5, 12, or 24 hours. No changes in basal kinase activity were induced by these chemicals at any of the times tested. Significant decreases in cytosolic and particulate PKC activity relative to controls were observed upon exposure of SMCs for 0.5 hours to 10 nM TCDD, TCDF, and DCDD. In contrast, SMCs exposed to TCDD and TCDF for 12 hours exhibited a significant increase in PKC activity in both cytosolic and particulate fractions. The PKC activity in cells exposed to DCDD for 12 hours was not altered. Prolonged exposure of SMCs to 10 nM TCDD, TCDF, and DCDD for 24 hours decreased PKC activity in the cytosolic fraction, while only TCDD and TCDF decreased particulate PKC activity. These data show that PKC activity is modulated differentially as a function of time in SMCs exposed to TCDD and related compounds. Collectively, the patterns of histone phosphorylation induced by these chemicals in rat aortic SMCs suggest that modulation of C‐kinase activity involves both receptor‐independent and receptor‐related events.
Characterization of heterologously expressed recombinant retinoic acid receptors with natural or synthetic retinoids
Authors: Kim Yang‐Won , Sharma Raghubir P. , Li Joseph K. K. 
Published: October 2006

AbstractThe first step in retinoid action is binding to their nuclear receptors. Therefore, characterization of binding characteristics of retinoids is of major importance. Human retinoic acid receptors α (hRARα), hRARβ, and mouse RARγ (mRARγ) were expressed heterologously in Escherichia coli as a recombinant glutathione S‐transferase (GST) fusion protein. The expressed fusion proteins were functional and bound specifically to the all‐trans‐retinoic acid (RA). The dissociation constants (Kd) for RA were 1.4 nM for GST‐hRARα, 1.4 nM for GST‐hRARβ, and 3.3 nM for GST‐mRARγ, respectively. The fusion proteins were further used for competitive displacement assays to determine the displacement constant (DC50) for other selected retinoids. All‐trans‐RA and 4‐oxo‐all‐trans‐RA have high affinity with all three receptors (DC50 = 0.8 ∼ 55 nM). The 13‐cis RA binds to hRARα with low affinity, but not to other RARs evaluated here. All‐trans‐N‐ethylretinamide, all‐trans‐retinylacetate, and an ethyl ester of tetrahydronaphthalene derivative had no affinity to any RARs. The hRARα and mRARγ receptors did not bind a naphthalene carboxylic acid derivative of RA, but hRARβ binds this chemical with high affinity. Results indicated that the three recombinant proteins were functional in binding various RA congeners. The affinity and binding data of these retinoids were compared to their observed teratogenic activity.
Absence of enantioselectivity in the pharmacodynamics of P450 2B induction by 5‐ethyl‐5‐phenylhydantoin in the male rat liver or in cultured rat hepatocytes
Authors: Nims Raymond W. , Sidhu Jaspreet S. , Thomas Paul E. , Mellini Donna W. , Nelson Victor C. , Omiecinski Curtis J. , Lubet Ronald A. 
Published: October 2006

AbstractTo explore the enantioselectivity of ligand interaction with the putative phenobarbital receptor, the pharmacodynamics of cytochrome P450 2B (CYP2B) induction by racemic 5‐ethyl‐5‐phen‐ylhydantoin and its two enantiomers were investigated in the male F344/NCr rat and in cultured adult male rat hepatocytes. Steady‐state serum drug concentrations, measured following 14 days of administration of the compounds in the diet (0‐1320 ppm, n = 3 rats per group), were used as an approximation of intrahepatocellular drug concentration. The serum xenobiotic concentrations associated with half‐maximal hepatic CYP2B induction were 5‐10 μM, based on measurement of pentoxy‐ or benzyloxyresorufin O‐dealkylation activities, or immunoreactive CYP2B1 protein. The corresponding potency values in the hepatocyte culture experiments were 8‐12 μM, based on measurement of total cellular RNA coding for CYP2B1. In both the in vivo and the hepatocyte culture experiments, the potencies for CYP2B induction were essentially equivalent for the racemate and the individual enantiomers of 5‐ethyl‐5‐phenylhydantion. In the case of this compound, there would appear to be no enantioselectivity for CYP2B induction. This finding may be interpreted as evidence against receptor mediation in the induction of CYP2B activity, although it is also possible that a receptor is involved that does not exhibit enantioselectivity.
Effect of phenobarbital and the peroxisome proliferator ciprofibrate on γ‐glutamyltranspeptidase activity and leukotriene C4 concentration in cultured rat hepatocytes
Authors: Hong Jin T. , Wilson Mary W. , Glauert Howard P. 
Published: October 2006

AbstractPeroxisome proliferators induce hepatocellular carcinomas in rodents by an unknown mechanism. γ‐Glutamyltranspeptidase (GGT), a biochemical marker for identifying putative preneoplastic lesions in the liver, is highly expressed in phenobarbital (PB)‐promoted altered hepatic foci but not in those promoted by peroxisome proliferators. One of the substrates of GGT is the eicosanoid LTC4. Because peroxisome proliferators and PB have differing effects on eicosanoid metabolism in vivo, we hypothesized that PB would similarly increase LTC4 concentrations, whereas the peroxisome proliferator ciprofibrate (CIP) would not. Cultured hepatocytes were treated with the peroxisome proliferator ciprofibrate (CIP: 100 and 400 μM) or PB (PB: 0.5 and 2 mM). Competitive radioimmunoassay (RIA) was used to determine the concentration of LTC4 in extracts of cultured hepatocytes. CIP decreased the concentration of LTC4 throughout the culture period, but PB increased the LTC4 concentration. Both doses of CIP significantly inhibited the induction of GGT activity at 48 and 72 hours, whereas PB enhanced GGT activity. We therefore hypothesized that LTC4, a substrate of GGT, may induce GGT activity. LTC4, however, did not enhance GGT activity and inhibited it at very high concentrations. The results of this experiment show that CIP and PB have different effects on GGT activity and LTC4 concentration. LTC4, however, does not induce GGT in cultured hepatocytes. © 1996 John Wiley & Sons, Inc.
Reduced glutathione esters—antidotes to toxicity. Cytotoxicity induced by hydrogen peroxide, 1‐chloro‐2,4‐dinitrobenzene, and menadione in murine P388D1 macrophages in vitro
Authors: Minhas Harjit S. , Thornalley Paul J. 
Published: October 2006

AbstractRepletion of depleted cellular reduced glutathione (GSH) levels in oxidative stress and exposure to arylating agents is a strategy for the development of antidotes to chemical toxicity. The effect of GSH, reduced glutathione ethyl monoester (GSHEt), and reduced glutathione ethyl diester (GSHEt2) on the cytotoxicity of hydrogen peroxide, 1‐chloro‐2,4‐dinitrobenzene (CDNB), and menadione to P388D1 macrophages in vitro was investigated. The median toxic concentration TC50 values of the toxicants were hydrogen peroxide 24 ± 2 mM (N = 19), CDNB 63 ± 6 μM (N = 18), and menadione 30 ± 4 μM (N = 22). Reduced glutathione, GSHEt, and GSHEt2 were poor antidotes to hydrogen peroxide toxicity. Indeed, the observed antidote effects were attributed to the nonenzymatic reaction of the GSH derivatives with hydrogen peroxide in the extracellular medium. Reduced glutathione ethyl diester was a more potent antidote of CDNB‐ and menadione‐mediated toxicity than GSHEt and GSH. For cell incubations with the approximate median toxic concentration TC50 values of hydrogen peroxide, CDNB, and menadione, the respective median effective antidote concentration EC50 values were GSHEt 23.8 ± 4.1 mM (N = 9), 3.6 ± 0.6 mM (N = 11), and 226 ± 93 μM (N = 12); and GSHEt2 20.4 ± 1.9 mM (N = 6), 603 ± 2 μM (N = 9), and 7.6 ± 2.3 μM (N = 12). Reduced glutathione ethyl diester was a potent antidote to CDNB‐ and menadione‐induced toxicities but not to hydrogen peroxide‐induced toxicity under acute intoxication conditions. © 1996 John Wiley & Sons, Inc.
Upregulation of glucose‐6‐phosphate dehydrogenase in response to hepatocellular oxidative stress: Studies with diquat
Authors: Cramer Clay T. , Cooke Susan , Ginsberg Leonard C. , Kletzien Rolf F. , Stapleton Susan R. , Ulrich Roger G. 
Published: October 2006

AbstractThe expression of hepatic glucose‐6‐phosphate dehydrogenase (G6PDH, E.C. 1.1.1.49) is hypothesized to be modulated by free radicals during oxidative stress. The ability of diquat, a compound known to enhance oxidative stress through generation of reactive oxygen species, to modulate the expression of G6PDH in primary cultures of Fischer‐rat hepatocytes was examined. Diquat‐treated hepatocytes maintained in a chemically defined medium showed both a time‐ and concentration‐dependent increase in G6PDH enzyme activity. This increase in enzyme activity was accounted for by an increase in both G6PDH mRNA and immunoreactive protein, suggesting control at a pretranslational level. The possibility that diquat increased transcription by transfecting cells with a chimeric gene containing 935 bp of the G6PDH promoter (‐878 to +57) linked to the gene for chloramphenicol acetyl‐transferase (CAT) was examined. Hepatocytes transiently transfected with this chimera, and subsequently treated with diquat, exhibited an increase in CAT activity. However, hepatocytes transfected with a chimera containing 287 bp of the G6PDH promoter (‐230 to +57) exhibited only basal CAT activity in the presence of diquat. These results suggest that regions in the DNA sequences required for diquat‐induced expression of G6PDH lie between base pairs ‐878 and ‐230 of the G6PDH gene. These findings are suggestive that oxidative stress in hepatocytes increased the expression of G6PDH activity and protein and that the increased expression is controlled at the transcriptional level. © 1996 John Wiley & Sons, Inc.
Lumbar body fusion with a bioresorbable cage in a goat model is delayed by the use of a carboxymethylcellulose‐stabilized collagenous rhOP‐1 device
Authors: Mullender Margriet G. , Krijnen Matthijs R. , Helder Marco N. , Smit Theo H. , Everts Vincent , Wuisman Paul I.J.M. 
Published: October 2006

AbstractThe purpose of this study was to evaluate the efficacy of recombinant human osteogenic protein‐1 (rhOP‐1) with a carboxymethylcellulose‐stabilized collagenous carrier as a bone graft substitute for instrumented lumbar spinal fusion in an established goat model. Twenty goats received a resorbable poly‐L‐lactic acid (PLLA) interbody cage packed with either rhOP‐1 and its carrier or autologous bone graft. The carrier material was bovine collagen type‐1 stabilized with carboxymethylcellulose. The fusion segments were retrieved at 3 or 6 months postimplantation and evaluated by radiographic and histologic analyses. The rhOP‐1 graft substitute, used in combination with the resorbable PLLA cage, showed inferior results as compared to autologous bone graft in the goat lumbar fusion model. Whereas four out of five segments from the autograft group were fused after 6 months, none of the four segments receiving the rhOP‐1 graft substitute were fused at this time point. Bone ingrowth into the cage was delayed or absent in the experimental group, whereas all autograft specimens showed advanced bone ingrowth (3 months) or fusion (6 months). We suggest that the fusion process was inhibited, because cells were unable to penetrate the rhOP‐1 graft material. This led to delayed bone formation and in some cases inadequate tissue formation. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:132–141, 2007
Medical informatics in context
Authors: Morris Theodore Allan , Assar Soraya , Detlefsen Ellen Gay , McKnight Michelynn 
Published: October 2006

AbstractMedical informatics may be defined as “the application of information science and information technology to the theoretical and practical problems of biomedical research, clinical practice, and medical education.” As such, it has become increasingly important as a unifying force‐and forum for exchange‐among cognate and contributory fields in biomedicine and information science. Accordingly, increasing numbers of knowledge workers are involved in or affected by medical informatics‐related programs and activities.This program will provide an overview of the field of medical informatics and illustrate how it “fits in” with other knowledge domains.The panelists will discuss the roles and relationships among medical informatics, bioinformatics, information science, and medical librarianship, and their implications for research, application, and education.
Design and evaluation of a prototype user interface supporting sharing of search knowledge in information retrieval
Authors: Zhang Xiangmin , Li Yuelin , Jewell Sarah 
Published: October 2006

AbstractThis paper describes a prototype user interface system, CIRR tool, which allows searchers to share their relevance judgments, search queries, and search results by providing a system Task Console with a “Group Report” feature. The system was developed based on the assumption that knowledge sharing in information retrieval (IR) is helpful and important to improve search performance. A usability evaluation of this system was conducted. The test results show that in general the system is easy to learn and use. However, some usability problems are also observed. The paper discusses these issues and proposes future research directions.
Virtual reference for video collections: System infrastructure, user interface and pilot user study
Authors: Mu Xiangming , Luo Lili 
Published: October 2006

AbstractA new video‐based Virtual Reference (VR) tool called VideoHelp was designed and developed to support video navigation escorting, a function that enables librarians to co‐navigate a digital video with patrons in the web‐based environment. A client/server infrastructure was adopted for the VideoHelp system and timestamps were used to achieve the video synchronization between the librarians and patrons. A pilot usability study of using VideoHelp prototype in video seeking was conducted and the preliminary results demonstrated that the system is easy to learn and use, and real‐time assistance from virtual librarians in video navigation is desirable on a conditional basis.
Managing and disseminating scientific data and information: A technical discussion
Authors: Qin Jian , Carroll Bonnie , Futrelle Joe , Jablonski Jon , Shawa Tsering Wangyal 
Published: October 2006

AbstractThe management of scientific data and information is becoming increasingly important as the data volume grows rapidly. Scientific data management is affected by many factors in policy, legal, and technical areas. What is involved in scientific data management? What is the status of research and development in this area? How are libraries and information institutions responding to this new area of collections and services? This panel brings experts in this area to address some of these questions.
Surveys of scientists and engineers: Ensuring reliable research evidence for good practice
Authors: Vaughan K. T. L. , Tenopir Carol , Brown Cecelia , Hemminger Bradley M. , Jablonski Jon 
Published: October 2006

AbstractInformation scientists around the globe have made tremendous progress in understanding how scientists and engineers find and use information by through the use of a wide variety of survey instruments. Librarians and publishers increasingly turn to the data generated by these instruments in an effort to design and implement information products and services that the scientific community needs and desires. Three researchers experienced in studying the information seeking behavior of academics will describe their current investigations distinguishing between the survey mechanisms found to be effective or ineffective. Discussion will be led and provoked by the moderator and reactor who both have experience providing library services to this community. The last third of the session will be an open discussion soliciting comments and questions about trends, survey design, and survey experiences.
Dual‐task performance as a measure of mental effort in searching a library system and the Web
Authors: Kim Yong‐Mi , Rieh Soo Young 
Published: October 2006

AbstractThis paper examines a dual‐task method for the assessment of mental effort during online searching, having the users engage in two tasks simultaneously. Searching was assigned as a primary task and a visual observation was set up as a secondary task. The study participants were asked to perform two searches, one on the Web and the other in a web‐based library system. Perceived search difficulty and mental effort for searching on the two types of systems were compared through participant self‐reports, dual‐task performance, and search log analysis. After the searches were completed, the subjects reported that library searching was more difficult to conduct and they had to concentrate more than when Web searching. However, the results of dual‐task performance do not reveal much difference in mental effort or concentration during searches in the two systems. Rather, they invested mental effort differently when viewing search results and reading retrieved documents. The findings indicate that a dual‐task method provides a useful technique to measure mental effort in online searching, and it has a great potential to be used to measure other aspects of information retrieval such as task complexity and multitasking information behavior.
Research classics and citation analysis
Authors: Wang Peiling , Bownas Jennifer 
Published: October 2006

AbstractResearch classics are recognized important works in a field. Citing authors' comments along with the classics were analyzed along with citation counts to identify the use contexts. In‐depth citation analysis of 11 highly cited classics show unusual longevity as highly cited works, strong associations with high co‐citations, a number of image‐makers contributing extremely high recitations, and diversity of citing journals. The nature of the classics was also investigated to shed lights on the success of the classics, reasons for low rate of citations to certain classics.
A hybrid approach to faceted classification based on analysis of descriptor suffixes
Authors: Loehrlein Aaron , Jacob Elin K. , Yang Kiduk , Lee Seungmin , Yu Ning 
Published: October 2006

AbstractThis study explores the construction of a faceted vocabulary that can be used as a mechanism for organizing Web‐based resources. After analyzing the manual process of faceted vocabulary construction using existing organizational structures to identify heuristics for automating the construction process, we modeled a hybrid, semi‐automatic approach to facet generation that integrates the strengths of manual and automatic methods. This approach is based on the organization of terms according to the meanings of their suffixes. Although this heuristic could not usefully organize the majority of terms of the lexicon bases to which it was applied, it nevertheless shows promise as a component of hybrid classification.
The digital museum in the life of the user
Authors: Chen Hsin‐liang , Marty Paul F. 
Published: October 2006

AbstractThis panel will explore the fascinating issue of the “digital museum in the life of the user.” As online museums, digital museum collections, and enhanced gallery devices become more common, it is important that we improve our understanding of how museum visitors make use of digital museum resources, online and in house. This panel, therefore, will discuss approaches to and the need for a better understanding of the users and usage of digital museums.