bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of pancellular toxicity in guinea pig lung by ingestion of oleylanilide
Authors: Das Salil K. , Mukherjee Shyamali , Desai Usha
Published: October 2006

Toxic oil syndrome (TOS), characterized by widespread thromboembolism, vasculotoxicity, and ARDS, develops in humans ingesting denatured edible oils. The mechanism(s) involved in targeted vasculocentric damage in this multisystem disorder is not known. Oleylanilide (OA) was synthesized and fed to male, young adult guinea pigs by gavage for 30 days at doses of 35, 50, and 100 mg/kg/day in groups of six animals each respective to weight. Controls were fed olive oil. Oleylanilide fed animals gained less weight than controls. At the end of experiment, right lungs were inflation fixed in appropriate fixative for histology and transmission electron microscopy (TEM) and left lungs were frozen at −70°C for biochemical analyses. The activity of glycerophosphate acyltransferase (GAT) and cholinephosphotransferase (CPT), two key enzymes involved in phospholipid biosynthesis, were decreased in lung due to OA ingestion. All doses of OA induced marked perivascular and peribronchoiolar monocytic infiltrates that often formed prominent nodules; segmental vascular smooth muscle cell proliferation and derangement of myocytic polarity, subendothelial foamy infiltrates, and edema; nuclear pyknosis and dropout in vascular and bronchial targetoid myocytes; and denudation of bronchiolar epithelial cells. Alveoli contained large numbers of monocytes, macrophages, red cells, edema, and debris. Transmission electron microscopy showed type I cell cytoplasmic ballooning and disintegration of type I cell; contracted and blebbed endothelial cells, fibrin thrombi in capillaries, intracellular megalamellar bodies in type II cells, and surfactant lamellae; and liposomes and fine granular precipitates within alveoli, and contraction and lift off of bronchiolar epithelial cells. Monocytes, mast cells, and eosinophils infiltrated bronchial walls. Furthermore, there was deposition of electron dense particles on the surface of the alveolar wall. Cytotoxicity of various cells is considered to be either directly caused by the anilides or a result of monocytes and free radicals. This is the first experimental model for “intractable” dysplastic vascular diseases in humans.
Cytosolic 5′‐nucleotidase/nucleoside phosphotransferase: A nucleoside analog activating enzyme?
Authors: Turriani Maura , Pesi Rossana , Nardone Antonella , Turchi Gino , Sgarrella Francesco , Ipata Pier Luigi , Tozzi Maria Grazia
Published: October 2006

Nucleoside phosphotransferase acting on inosine and deoxyinosine has been partially purified from cultured Chinese hamster lung fibroblasts (V79). The activity is associated with a cytosolic 5′‐nucleotidase acting on IMP and deoxyIMP. The transfer of the phosphate group from IMP to inosine catalyzed by this enzyme was activated by ATP and 2,3‐bisphosphoglycerate. Inosine, deoxyinosine, guanosine, deoxyguanosine, and the nucleoside analogs 2′,3′‐dideoxyinosine and 8‐azaguanosine are substrates, while adenosine and deoxyadenosine are not. IMP, deoxyIMP, GMP, and deoxyGMP are the best phosphate donors.

The cytosolic 5′‐nucleotidase/phosphotransferase substrate, 8‐azaguanosine, was found to be very toxic for cultured fibroblasts (LD50 = 0.32 μM). Mutants resistant to either 8‐azaguanosine and the correspondent base 8‐azaguanine were isolated and characterized. Our results indicated that the 8‐azaguanosine‐resistant cells were lacking both cytosolic 5′‐nucleotidase and hypoxanthine‐guanine phosphoribosyltransferase, while 8‐azaguanine resistant cells were lacking only the latter enzyme. Despite this observation, both mutants displayed 8‐azaguanosine resistance, thus indicating that cytosolic 5′‐nucleotidase is not essential for the activation of this nucleoside analog.
Significance of TCDD‐induced changes in protein phosphorylation in the adipocyte of male guinea pigs
Authors: Enan Essam , Matsumura Fumio
Published: October 2006

The chemical TCDD (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin) at very low concentrations has been found to cause a rapid rise in protein phosphorylation activities in the extranuclear fraction (i.e., cytosol and cellular membranes) of the adipose tissue from male guinea pigs. The effect occurred both in vivo and when TCDD was added to adipose in tissue culture (in situ). To study the cause for such a TCDD‐induced biochemical change, isolated adipose tissues were treated with TCDD in conjunction with various diagnostic agents known to affect protein synthesis (actinomycin D and cycloheximide) and protein phosphorylation activities (genistein). The stimulatory effect of TCDD on protein phosphorylation was not totally abolished by actinomycin D; however, cycloheximide and genistein partially suppressed the effect of TCDD. Such an action of TCDD was accompanied by a quick rise in ras GTP binding activity as well as a rise in phosphorylation of nuclear c‐myc protein product within 10 minutes after TCDD addition, indicating that TCDD is likely to activate the signal transduction pathway for growth factors. In view of the absence of an inhibitory action of actinomycin D and the short time required for TCDD to induce these changes, we have formulated a working hypothesis that stimulation of protein phosphorylation activities by TCDD may not be mediated by a transcriptional process. To test this possibility, an extranuclear fraction was obtained from the homogenate of adipose tissue, and the effect of TCDD was studied in vitro cell‐and nucleus‐free conditions. It was found that TCDD was capable of activating protein phosphorylation activity under cell free conditions even in the absence of nuclei. Such an action of TCDD is dependent on the action of the Ah receptor.
Multiple activation of chloroform in kidney microsomes from male and female DBA/2J mice
Authors: Ade Paola , Guastadisegni Cecilia , Testai Emanuela , Vittozzi Luciano
Published: October 2006

Microsomes from the renal cortex of DBA/2J mice can metabolize chloroform through oxidative and reductive pathways, similar to hepatic microsomes.

The oxidative or reductive nature of CHCl3 activation is strictly dependent on the oxygenation of the incubation mixture, as indicated by the formation of qualitatively different adducts to phos‐pholipids (PLs).

The protein and lipid binding levels measured in kidney microsomes from control females differed significantly from the binding levels observed with kidney microsomes from male and testosterone‐treated female DBA/2J mice in aerobic conditions only. Therefore, the sex‐dependent CHCl3‐induced acute nephrotoxicity seems related only with the oxidative CHCl3activation.

The levels of adducts to PL polar heads and to protein showed a strict correlation with each other. Therefore, the assay of adducts to PL polar heads may be used as a substitute for the assay of adducts to protein. This might be especially convenient when studying the effects of both phosgene and the trichloromethyl radicals.
A comparative study of inhibition of acetylcholinesterase, trypsin, neuropathy target esterase, and spleen cell activation by structurally related organophosphorus compounds
Authors: Pruett Stephen B. , Chambers Howard W. , Chambers Janice E.
Published: October 2006

Organophosphorus (OP) compounds can bind to and inactivate several target molecules other than acetylcholinesterase (AChE). In the present study, five sets of structurally related organophosphorus compounds were used to evaluate the relationships between organophosphorus binding sites of AChE, neuropathy target esterase (NTE), trypsin, and the target molecule(s) involved in inhibition of splenocyte activation by OP compounds. The concentration of each OP compound required to inhibit enzyme activity or splenocyte activation by concanavalin A by 50% was determined. The pattern of IC50 values indicated that AChE, trypsin, NTE, and the molecule(s) involved in inhibition of splenocyte activation are distinct with regard to patterns of inhibition by OP compounds. However, there was a striking similarity in the patterns of inhibition for trypsin and NTE with substantial differences for only 2 of 20 compounds. This pattern suggests similarity in the active sites of these molecules. There were also similarities in the IC50 patterns for lymphocyte activation and trypsin or NTE activity. However, the correlation was not as strong as between NTE and trypsin, and the data suggested the possibility of multiple target molecules for inhibition of splenocyte activation by OP compounds. More importantly, there was essentially no correlation between the pattern of IC50 values for AChE and splenocyte activation. This strongly suggests that acetylcholine and AChE of the type found in the brain are not important in the regulation of splenocyte activation by concanavalin A.
2,3,7,8‐tetrachlorodibenzo‐p‐dioxin induced alterations of pyruvate carboxylase levels and lactate dehydrogenase isozyme shifts in C57BL/6J male mice
Authors: Sparrow Barney R. , Thompson Cynthia S. , Ryu Byung‐Woo , Selevonchick Daniel P. , Schaup Henry W.
Published: October 2006

A dose‐dependent reduction of hepatic pyruvate carboxylase levels and activity occurs in C57BL/6J male mice given 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) i.p. in a corn oil carrier. The dose range was from 1 to 75 μg/kg body weight and the analysis was done 8 days postinjection. At the maximum TCDD level investigated, we found a 10‐fold reduction in pyruvate carboxylase activity. Furthermore, TCDD at a dose of 1 μg/kg body weight blocks corn oil induction of an increase in the amount of pyruvate carboxylase in liver protein extracts. At doses beyond those required to initiate a reduction in pyruvate carboxylase, lactate dehydrogenase isozyme patterns shift. This is accompanied by an increase in blood lactic acid levels. We propose that TCDD‐mediated reduction in pyruvate carboxylase and lactate dehydrogenase isozyme shifts may represent a major component in TCDD toxicity.
Age‐related differences in TGF‐α and proto‐oncogenes expression in rat liver after a low dose of carbon tetrachloride
Authors: Dalu Abraham , Cronin Gerald M. , Lyn‐Cook Beverly D. , Mehendale Harihara M.
Published: October 2006

The resiliency of rats during early postnatal development to CCl4 or to an interactive hepatotoxicity of chlordecone (CD) + CCl4 has been shown to be due to an efficient stimulation of tissue repair. The objective of the current study was to investigate if this is due to efficient expression of transforming growth factor‐α (TGF‐α) and proto‐oncogenes. Postnatally developing (20 day old) and adult (60 day old) male Sprague–Dawley rats were challenged with a single low dose of CCl4 (100 μL/kg, ip) or corn oil. Liver samples were collected during a time course (0–96 h) after the administration of CCl4 and used to examine TGF‐α and early (c‐fos) and late (H‐ras and K‐ras) proto‐oncogenes mRNA expressions. Significant increases in TGF‐α, H‐ras, and K‐ras gene expressions were evident as early as 12 hours after CCl4 and peaked between 24 and 48 hours in an age‐dependent manner as detected by slot‐blot analysis. Results of the study revealed three‐ and twofold increases in TGF‐α gene expression in 20 and 60 day old rats, respectively, after CCl4. There were 3.5‐ and 2.5‐fold increases in H‐ras and 4.4‐ and 3.4‐fold increases in K‐ras in 20 and 60 day old rats, respectively. In contrast, a 10‐fold increase in c‐fos mRNA expression was evident in 20 day old rats 1 hour after CCl4 treatment, returning to the baseline value by 3 hours, whereas in 60 day old rats, this increase was less than twofold. The overall findings of this study indicate that TGF‐α and the early and late proto‐oncogene mRNA expressions were enhanced in an age‐ and time‐dependent manner in response to a low dose of CCl4. These results further strengthen the view that the remarkable resiliency of rats to hepatotoxicants during early postnatal development is due to substantial increases in stimulation of hepatocellular regeneration and tissue repair mechanisms, leading to regression of liver injury and recovery. © 1996 John Wiley & Sons, Inc.
Mechanism of toxicity of precocene II in rat hepatocyte cultures
Authors: Hammond Alison H. , Garle Michael J. , Fry Jeffrey R.
Published: October 2006

Precocene II was more toxic in 24 hour cultures than in 72 hour cultures of rat hepatocytes. In 24 hour cultures, there was no observable toxicity at 75 μM precocene II after exposure for 6 hours, but after 24 hours, 65% of the cells were dead. In contrast, although 794 μM killed 50% of the cells in the 72 hour cultures after a 24 hour exposure, 1 mM killed 96% of the cells within 6 hours. In both 24 and 72 hour cultures, cell death was preceded by a rapid, early loss of mitochondrial membrane potential, followed by decreases in glutathione, reduced pyridine nucleotide status, and plasma membrane Na+/K+‐ATPase activity. There was also a rapid loss of ATP in the 72 hour cultures but not in the 24 hour cultures; therefore, onset of cell death may be closely linked to loss of ATP. Inhibition of cytochrome P‐450 prevented the toxicity, and partially protected against the loss of membrane potential and glutathione, in 24 hour cultures but was ineffective in 72 hour cultures. Therefore, in addition to depletion of glutathione, precocene II appears to damage mitochondria and plasma membrane functions and can do so by more than one pathway. © 1996 John Wiley & Sons, Inc.
Differential regulation of cytochrome P450 3A1 and P450 3A2 in rat liver following dexamethasone treatment
Authors: Choudhuri Supratim , Zhang Xu Jie , Waskiewicz Mark J. , Thomas Paul E.
Published: October 2006

Induction of P450 3A1 and P450 3A2 was studied in adult rat liver following treatment with a single high dose of dexamethasone (DEX). The increase of both P450 3A1 and 3A2 occurred at the level of mRNA as well as protein. P450 3A isozymes thus induced were catalytically active. No constitutive expression of P450 3A1 mRNA or protein was observed in males or females. Constitutive expression of P450 3A2 mRNA and protein was observed in males but not in females. Additionally, in females, P450 3A2 was almost nondetectable compared to that in males, at any dose of DEX. A time course study following DEX treatment showed that P450 3A1 mRNA and protein were detectable in both sexes at 12 hours, increased until 48 hours, and then declined. The decline was more rapid in males. P450 3A2 mRNA and protein increased as early as 3 hours, increased further up to 48 hours, and slowly declined thereafter. A dose‐response study indicated that P450 3A1 mRNA and protein progressively increased in both sexes from a dose of 30 mg/kg. In contrast, P450 3A2 mRNA and protein in males did not increase up to a dose of 30 mg/kg but increased at higher doses. Total P450 content and P450 3A catalytic activity were also found to increase with time and dose. © 1996 John Wiley & Sons, Inc.
Ricin disturbs calcium homeostasis in the rabbit heart
Authors: Ma Lianmin , Hsu Chia‐Hsuh , Fugate Robert , Patterson Eugene , Thadani Udho , Robinson Casey P.
Published: October 2006

Ricin, a toxic lectin from the castor bean, affects the cardiovascular system. Because calcium is very important in cardiotoxicity and cell intoxication, we studied the effects of ricin pretreatment to rabbits on basal intracellular calcium levels and calcium uptake and release from isolated papillary muscle, microsomes, and mitochondria. An increase in basal intracellular calcium levels was observed. Ricin pretreatment nearly doubled the intracellular‐free Ca2+ concentration as measured by fura‐2 fluorescence microscopy in isolated myocytes (p = 0.002). Ricin did not alter basal calcium efflux in isolated papillary muscles. However, ricin inhibited the NE‐induced calcium efflux (expressed as fractional efflux ratios) in papillary muscles from rabbits receiving the minimum lethal dose of ricin at 25–35 minutes (p = 0.002 and 0.003, respectively). Ricin depressed basal calcium uptake into isolated papillary muscles at 5 minutes (mean ± SEM, μmol/g wet weight) (control: 3.68 ± 0.57; ricin: 2.31 ± 0.28, p = 0.045, n = 6). Ricin pretreatment significantly depressed calcium uptake into microsomes (mean ± SEM, μmol/g protein) (control: 9.9 ± 1.9; ricin: 3.1 ± 1.9, p = 0.025, n = 6). Calcium uptake into mitochondria was increased at the beginning (2 minutes, p = 0.048), but not thereafter. Thus, administration of ricin disturbed calcium homeostasis in the rabbit heart, which may be at least partially responsible for altering cardiac function and myocardial cell death. © 1996 John Wiley & Sons, Inc.
Functional expression of voltage‐gated sodium channels in primary cultures of human cervical cancer
Authors: Diaz Daniel , Delgadillo Dulce Maria , Hernández‐Gallegos Elizabeth , Ramírez‐Domínguez Martha Eugenia , Hinojosa Luz María , Ortiz Cindy Sharon , Berumen Jaime , Camacho Javier , Gomora Juan Carlos
Published: October 2006

Cervical cancer (CaC) is the third most frequent cause of death from cancer among women in the world and the first in females of developing countries. Several ion channels are upregulated in cancer, actually potassium channels have been suggested as tumor markers and therapeutic targets for CaC. Voltage‐gated sodium channels (VGSC) activity is involved in proliferation, motility, and invasion of prostate and breast cancer cells; however, the participation of this type of channels in CaC has not been explored. In the present study, we identified both at the molecular and electrophysiological level VGSC in primary cultures from human cervical carcinoma biopsies. With the whole cell patch clamp technique, we isolated and identified a voltage‐gated Na+ current as the main component of the inward current in all investigated cells. Sodium current was characterized by its kinetics, voltage dependence, sensitivity to tetrodotoxin (TTX) block and dependence to [Na+]o. By analyzing the expression of mRNAs encoding TTX‐sensitive Na+ channel α subunits with standard RT‐PCR and specific primers, we detected Nav1.2, Nav1.4, Nav1.6, and Nav1.7 transcripts in total RNA obtained from primary cultures and biopsies of CaC. Restriction enzyme analysis of PCR products was consistent with the molecular nature of the corresponding genes. Notably, only transcripts for Nav1.4 sodium channels were detected in biopsies from normal cervix. The results show for the first time the functional expression of VGSC in primary cultures from human CaC, and suggest that these channels might be considered as potential molecular markers for this type of cancer. J. Cell. Physiol. 210: 469–478, 2007. © 2006 Wiley‐Liss, Inc.
Using lessons from health care to protect the privacy of library users: Guidelines for the de‐identification of library data based on HIPAA
Authors: Nicholson Scott , Smith Catherine Arnott
Published: October 2006

While libraries have employed policies to protect the data about use of their services, these policies are rarely specific or standardized. Since 1996 the U.S. healthcare system has been grappling with the Health Insurance Portability and Accountability Act (HIPAA), which is designed to provide those handling personal health information with standardized, definitive instructions as to the protection of data. In this work, the authors briefly discuss the present situation of privacy policies about library use data, outline the HIPAA guidelines to understand parallels between the two, and finally propose methods to create a de‐identified library data warehouse based on HIPAA for the protection of user privacy.
Navigational characteristics of e‐document readers
Authors: Qayyum Asim , Bilykh Igor
Published: October 2006

The purpose of this study was to examine the navigational patterns of graduate students' text markings when they interact with electronic documents during an active reading process, thus taking on the role of authors. The readings took place in two settings, private and document sharing, where in the latter environment each document was shared among a group of students. The resulting interaction was monitored and electronically logged for each of these environments, which then provided us with user‐navigational patterns taxonomy. Descriptive and statistical tests were carried out on the activities observed within this taxonomy to develop a framework for comparing the reading patterns for readers working in individual and document sharing environments. This framework was then used to obtain user feedback during the interview sessions that were held with the participants of this study. Because of our investigation, we were able to create a set of specific recommendation that system designers can use in order to create better, more intuitive, and userfriendly electronic reading and marking systems.
How neutral can technology be?
Authors: Caidi Nadia , Shankar Kalpana , Dalbello Marija , Froehlich Thomas J.
Published: October 2006

Is technology amoral? Is design value‐laden but code neutral? While philosophers, technologists, science and technology studies (STS) scholars, and social critics continue to debate whether or not information technologies are neutral and an autonomous force acting independently of other social processes, these discussions are only marginally addressed in Information studies. Yet, discussing these issues is of compelling importance for the training of the next generation of information professionals. The differing assumptions and values about the social nature of technology have implications for research and practice, and are of compelling importance from an ethics, design, policymaking and globalization perspective. This panel will address the varying approaches (e.g., instrumental theory of technology versus more interpretive approaches) and discuss the implications of technological (non) neutrality in a variety of settings, including ubiquitous computing, health care technologies, digital library development, and others.
Sparking synergies between research and practice: The contribution of social informatics
Authors: Rosenbaum Howard , Sawyer Steve , Davenport Elisabeth , Day Ronald
Published: October 2006

The purpose of this panel is to address the relationships among research and practice in the domain of information systems in organizations. Using the perspective of social informatics, we highlight issues with current work, areas of particular interest, and problems vexing both professional and scholarly interests
Putting motion into the image retrieval interface
Authors: Hastings S. K. , Lewis Elise , Rorissa Abebe , Schmidt Michael , Turner James
Published: October 2006

When video, still and 3D images meet, how do we design a universal interface? This panel looks at current research in the imaging field focused on bridging the gap between image retrieval system designers and users. Creating interfaces that move with the format in heterogeneous databases is only part of the challenge.

This panel brings together a wide range of research from the imaging field. It is important to monitor the progress of the imaging field since user expectation, technology and information needs are constantly changing. Current research, such as the research offered in this panel, will help the practitioners and system designers meet the information needs of all the stakeholders involved.
Annotation as process: A vital information seeking activity in historical geographic research
Authors: Ruvane Mary B.
Published: October 2006

This paper describes the role annotations played in evolving and growing the value of a research database in the framework of an historical geographer's information seeking process. The database was designed as a “note‐taking” tool for gathering historical evidence from primary source documents. The individual facts collected at first provided little utility to the researcher, indicative of Buckland's (1991) information‐as‐thing. As the process of collecting data began to amass a large body of material the geographer's information needs grew as new connections were made between the accumulating annotations.
Relevance criteria used by teachers in selecting oral history materials
Authors: Lawley Katy Newton , Soergel Dagobert , Huang Xiaoli
Published: October 2006

From a user‐centered and task‐specific perspective on relevance, we studied the relevance criteria used by teachers ‐ an understudied but important group ‐ who were searching for materials to use in the classroom to support learning on a particular theme. We observed teachers planning lessons and searching an archive of videotaped Holocaust survivor testimonies; the archive was created by the Survivors of the Shoah Visual History Foundation who interviewed 52,000 survivors and systematically cataloged the resulting testimonies. The teachers used a collaborative process to design lesson plans and search for appropriate testimony passages; they employed an array of relevance criteria that pertain specifically to teaching. The objectives implied in their criteria correspond to the teaching objectives described in lesson plans and teacher interviews, including connecting with students, representing diversity, and teaching tolerance. Our findings suggest user‐oriented design approaches that support retrieval of instructional materials and collaboration in line with the needs and knowledge of teachers.
Distance education: How are we doing, and how do we know?
Authors: Hastings Sam , Gregory Vicki , Montague Rae‐Anne , Lester June
Published: October 2006

The directory of ALA‐accredited master's programs in library and information science indicates that almost half enable students to complete the degree either wholly or substantially online, and a similar (not necessarily overlapping) number offer courses in locations remote from the main campus. The IMLS‐funded Web‐based Information Science Education (WISE) consortium is gaining interest and new members. The question is no longer “should we do distance education?”, but “how are we doing, and can we do it better?” What do the data tell us about successes and failures? How have we undertaken to evaluate our distance education activities? Do we have comparative results? A group of panelists from institutions which have pioneered distance education in library and information science will address these issues.
Digital resources for dentistry database: A needs assessment
Authors: Paling Stephen , Miszkiewicz Melissa
Published: October 2006

This poster session will describe a current needs assessment at the University at Buffalo that is designed to determine how a collection of digitized dental slides can meet the needs of dental researchers and practitioners. The University's School of Dental Medicine houses several collections of dental slides that depict various pathological conditions of the mouth and maxillofacial region, as well images of various human tissue types. These collections present a rich set of possibilities for pedagogical and diagnostic use by members of the dental profession. Previous studies have not directly addressed the description, organization, and use of digitized dental images, and how those efforts can address the needs of dental professionals. This leaves a gap in the research that this needs assessment can begin to fill.
Toward information retrieval Web services for digital libraries
Authors: Fu Yueyu , Mostafa Javed , Ke Weimao
Published: October 2006

Information retrieval (IR) functions serve a critical role in many information systems. There are many techniques and operations have been developed in IR that do not require radical changes or re‐implementation. The implemented IR algorithms can be distributed or their functions made available through the framework of web services. A key idea behind web services is that frequently used functions can be implemented once and offered to other application or software environments through programmatic interfaces. Web services in the IR domain have not been widely tested. Library of User‐Oriented Concepts for Access Services (LUCAS) offers IR functions such as term extraction, term clustering, and document classification as web services. It has successfully served other information systems such as the Biological Knowledge through Ontologies (BioKnOT) and the Extensible Networked Association‐based Bioinformatics Learning Environment (ENABLE) Knowledge Base. In this paper, we demonstrate the utility of LUCAS to the ENALBE system.
Consolidating user relevance criteria: A meta‐ethnography of empirical studies
Authors: Bales Stephen , Wang Peiling
Published: October 2006

The purpose of this study is to bring together empirical studies on user‐based relevance criteria and to provide a conceptual framework for the organization of factors affecting relevance judgments and information selection. Through systematic analysis applying a meta‐ethnographic approach we cluster compatible relevance criteria definitions and resolve semantic differences of the same named criteria with diverse definitions. The consolidated criteria are factored into four dimensions: situational factors pertaining to user's context, task, and cognitive and affective states, user criteria pertaining to users' perceptions and needs, document information elements (DIEs) pertaining to information attributes, and value judgments pertaining to what an information object means to the user). For further investigation, we propose a set of matrices to depict the relationships between dimensions as an effective tool for developing a better understanding of the relationship and interaction between users' relevance factors. These relationships can guide IR system design and improvements.
Searching the “deep” Web for medical information: Reflections from a healthcare information researcher
Authors: Heath Angela
Published: October 2006

As a researcher of medical equipment, my job is to provide informational support to engineers and architects who build healthcare facilities. Because the information requested is technical and specific, it is often times not available by performing searches on the World Wide Web. In order to perform the job and fulfill information requests, it is often necessary to search in deeper levels of the Web. This paper reflects upon the experiences and practices that I have developed which utilize traditional and current technologies.
Personal information management in the present and future perfect: Reports from a special NSF‐sponsored workshop
Authors: Jones William , Bruce Harry , Bates Marcia J. , Belkin Nicholas , Bergman Ofer , Marshall Cathy
Published: October 2006

In an ideal of personal information management or PIM, people always have just the right information, in the right form and at the right place, to meet their current information needs. Panelists all participated in a special workshop sponsored by the National Science Foundation to consider the challenges of PIM that must be met in order to make significant progress towards this ideal. Panelists will discuss key challenges of and promising approaches to PIM. Approaches discussed involve not only high‐technology tools but also practical, teachable everyday techniques of PIM. Panelists will also discuss what it means to foster a research community for the field of PIM inquiry. Although panelists will use their experiences at the workshop as a starting point, discussion will freely range beyond the workshop to a general discussion of PIM. The panel is structured to maximize interaction among the panelists themselves and with the audience.
Pyrrolizidine alkaloids from Werneria nubigena
Authors: Roeder Erhard , Bourauel Thomas , Theisen Ingeborg
Published: October 2006

Four toxic pyrrolizidine alkaloids were isolated from Werneria nubigena and their structures determined by spectroscopic methods. © 1992 Wiley‐Liss, Inc.
Chemistry of sulphur‐bound pyrrolic metabolites in the blood of rats given different types of pyrrolizidine alkaloid
Authors: Mattocks A. Robin , Jukes Rebekah
Published: October 2006

Rats were injected with the pyrrolizidine alkaloids heliotrine, indicine, or anacrotine, and killed after 20 hr. Alkaloid metabolites conjugated to haemoglobin thiol groups were recovered in the form of pyrrolic monoethyl ethers, by treating blood samples with ethanolic silver nitrate under “buffered” conditions. Chemically prepared putative toxic metabolites of the alkaloids—dehydroheliotrine, dehydroindicine, and dehydroanacrotine—were also allowed to react in vitro with blood and with an immobilized thiol, thiol‐Sepharose, and subsequently the S‐conjugated pyrroles were again recovered as ethyl ethers. The recovered pyrrolic ethers were identified by comparing them with reference compounds prepared from ethanol and the dehydro‐alkaloids, and the structures of the S‐bound pyrroles were deduced. Blood from rats given the 9‐monoester alkaloids heliotrine or indicine contained pyrrolic residues, S‐bound at their 9‐position. Anacrotine‐treated rats yielded two diastereomeric 7‐ethers, showing that dehydrocrotanecine 7‐conjugates had been present in the blood. The products from alkaloid‐treated rats were identical with those from blood or thiol‐Sepharose treated with the corresponding dehydro‐alkaloids in vitro. This supported the view that proximal metabolites leading to S‐binding in vivo were the dehydro‐derivatives of the alkaloids. In each case the thiols were attacked by the most reactive centre of the dehydro‐alkaloid: the 9‐ester in dehydroheliotrine and dehydroindicine, and the 7‐ester in dehydroanacrotine. Accordingly, simple chemical reactions could account for the products formed in vivo.

The identification of S‐conjugated pyrrolic metabolites on haemoglobin provided evidence of the type of alkaloid ingested. This would have diagnostic value for pyrrolizidine poisoning of livestock or humans. Thus, 9‐monoesters of heliotridine or retronecine would lead to 9‐conjugates; 7,9‐diesters (such as monocrotaline) would give 7‐conjugates; and anacrotine exposure would be distinguishable by giving two isomeric 7‐conjugates.

The demonstration of S‐bound pyrroles on haemoglobin in rats exposed to indicine for less than 15 min illustrated the rapidity with which reactive metabolites are liberated after pyrrolizidine alkaloid ingestion. © 1992 Wiley‐Liss, Inc.
Anti‐tumor activity of T‐2 toxin‐conjugated A7 monoclonal antibody (T‐2‐A7 MoAb) against human colon carcinoma
Authors: Kojima Shuji , Nakamura Namie , Ueno Yoshio , Yamaguchi Toshiharu , Takahashi Toshio
Published: October 2006

Monoclonal antibody A7 (A7 MoAb), from splenocytes of a mouse immunized against human colorectal carcinoma, was used as a T‐2 toxin (T‐2) carrier targeting colon cancer. T‐2 was converted to T‐2 hemiglutarate by glutaric anhydride treatment, and T‐2‐A7 MoAb conjugates containing up to 20 T‐2 per antibody molecule were obtained from the antibody and T‐2 hemiglutarate activated with N‐hydroxysuccini‐mide. The in vitro cytotoxicity against human colon cancer (LS174T) cells indicated that the conjugates were markedly less toxic than the toxin itself. The immunoreactivity was evaluated from the in vitro binding activity of A7 MoAb with LS174T cells, and from the in vivo localization in LS174T‐bearing nude mice; it remained essentially intact after conjugation with T‐2. The efficacy of the T‐2‐A7 MoAb conjugate was tested against LS174T‐bearing nude mice. The conjugate significantly suppressed the growth of the tumor in comparison with both phosphate‐buffered saline and free T‐2. These results suggest that the conjugate of T‐2 with A7 MoAb might be useful as a selective immunotoxin for cancer immunotherapy, with less serious side effects than T‐2. © 1992 Wiley‐Liss, Inc.
Ochratoxin a in plasma of norwegian swine determined by an HPLC column‐switching method
Authors: Langseth Wenche , Nymoen Ulf , Bergsjø Bjarne
Published: October 2006

A method well suited for screening large numbers of plasma samples for ochratoxin A is presented. Proteins were precipitated with methanol and the supernatant diluted with 0.01 M phosphoric acid before 1 ml extract was injected into a high‐performance liquid chromatograph (HPLC). The extract was further cleaned up and pre‐concentrated on a polystyrene‐divinylbenzene precolumn. After column‐switching, the sample was chromatographed on a C18 analytical column, and ochratoxin A was detected with a fluorescence spectrophotometer, either directly or after postcolumn pH shift. The detection limit was 0.10 ng ochratoxin A/ml plasma. The method was used to determine the ochratoxin A concentration in 216 samples of swine plasma. They were collected from different herds in June 1991 from ten slaughterhouses, located in different parts of Norway. Eighty‐two percent of the samples contained ⩾0.10 ng ochratoxin A/ml plasma while 0.9% contained ⩾ 5.0 ng/ml. © 1992 Wiley‐Liss, Inc.
Chemical properties of the natural neurotoxin of Lathyrus sativus 3‐N‐oxalyl‐2,3‐diamino‐propanoic acid (β‐ODAP), its nontoxic 2‐N‐oxalyl isomer, and its hydrolysis product 2,3‐diamino‐propanoic acid (DAPRO) by 1H‐ and 13C‐NMR spectroscopy
Authors: De Bruyn André , Van Haver Dirk , Lambein Fernand , Abegaz Berhanu M.
Published: October 2006

The 1H and 13C NMR data of DAPRO, α and β‐ODAP were measured at varying pH values and the physical relevance of these data was studied. As a potential way to detoxify the neurotoxin β‐ODAP, its isomerization was studied at room temperature and at 60°C. An unknown hydrolysate is identified as DAPRO. © 1992 Wiley‐Liss, Inc.
Effect of okadaic acid on the cytotoxic activity of Clostridium difficile toxin B and Clostridium sordellii toxin L
Authors: Baldacini Olivier , Lutun Philippe , Girardot Raymonde , Monteil Henri
Published: October 2006

Clostridium difficle toxin B and Clostridium sordellii toxin L, which are immunologically related toxins, possess a cytotoxic activity inducing depolymerization of microfilaments and cellular retraction of cell bodies that are different for toxin B‐ and toxin‐L‐treated cells. The biological mechanisms responsible for these effects are unknown, but a previous study revealed that both toxins induce modification of phosphorylation of cellular proteins extracted from toxin B‐ and toxin L‐treated cells without changes in protein kinase C activity or cAMP concentration. In the present study, we have investigated the effect of okadaic acid, an inhibitor of protein phosphatases, on the cytotoxic activity of toxins B and L in MacCoy cells. Firstly, we reveal by cytotoxic assay and staining of F‐actin that okadaic acid (1 μM or higher) induces depolymerization of microfilaments and cellular morphological modifications which are similar to that of cells treated with toxin L. Secondly, we show that 1 μM okadaic acid potentiates the cytotoxic activity of toxin L but not of toxin B. These observations suggest that the cytotoxic mechanisms induced by okadaic acid and toxin L treatment are partly common, indicating that an increase in phosphorylation favors the cytotoxicity of toxin L. Since okadaic acid had no influence on the cytotoxicity of toxin B, we suggest that toxin B and L, alter the cells by different cellular biological mechanisms. © 1992 Wiley‐Liss, Inc.
Fusapyrone and deoxyfusapyrone, two antifungal α‐Pyrones From Fusarium semitectum
Authors: Evidente Antonio , Conti Luigi , Altomare Claudio , Bottalico Antonio , Sindona Giovanni , Segre Anna Laura , Logrieco Antonio
Published: October 2006

A strain of Fusarium semitectum Berk. & Rav. from maize stalk rot in southern Italy produced bioactive metabolites when cultured on autoclaved rice kernels at room temperature for 4 weeks. The organic extracts of fungal culture showed a strong antibiotic activity towards Geotrichum candidum in disk diffusion assays, but they were not toxic to Artemia salina larvae. Two antifungal metabolites were isolated and characterized by chemical and spectroscopic methods as two 3‐substituted‐4‐hydroxy‐6‐alkyl‐2‐pyrones, in particular, the 3‐(4‐deoxy‐β‐xylo‐hexopyranosyl)‐4‐hydroxy‐6‐[‐hydroxy‐7‐hydroxymethyl‐1,1,5,9,11‐pentamethyl‐3,5,8‐heptadecatrienyl]‐2H‐pyran‐2‐one and its 6‐[2‐hydroxy‐1,1,5,7,9,11‐hexamethyl] analog, which were named fusapyrone and deoxyfusapyrone, respectively. © 1994 wiley‐Liss, Inc.
Pharmacokinetic fate of 14C‐Labelled fumonisin B1 in Swine
Authors: Prelusky Dan B. , Trenholm H. Locksley , Savard Marc E.
Published: October 2006

The pharmacokinetics of the mycotoxin fumonisn B1 (FB1) were investigated in pigs. Animals were administered 14C‐FB1 intravenously (IV; 0.25 μCi, 0.40 mg/kg) or intragastrically (IG;0.35 μCi, 0.50 mg/kg); separate groups of pigs undewent bile cannulation prior to dosing (groups IV/B and IG/B, respectively). Blood, urine, faeces, (and bile), were collected at specific time intervals over 72 gr, and assayed for specific activity. Following IV dosing, plasma concentration‐time profiles were triexponential, with the following mean values: t½ α, 2.2 min; t½ β, 10.5 min; t½ γ 182 min; apparent volume distribution (Vdγ), 2.4 1 kg−1; plasmaclearance, 9.1 ml min−1 kg−1. After 3 days, clearance of FB1‐derived radioactivity from the body had slowed to trace levels; total recoveries in urine and faeces were 21.2% and 58.3%, respectively. In bile‐interruped pigs (IV/B) the absence of the slow terminal elimination phase (γ) suggested FB1 underwent enterohepatic circulation. Biliary recovery was 70.8% of the IV‐dose. Radioactivity remaining in tissues after 72 hr amounted to 19.8% and 11.9% of the dose given to IV and IV/B pigs, respectively; highest activities were measured in liver and kidney equivalent to 1,076 and 486 ng FB1, and/or metabolites per g tissue, respectively. Based on plasma and excretion data, systemic bioavailability following IG dosing was estimated to be a very limited 3‐4%. Tissue residue levels following IG dosing were 10‐20‐fold less than IV dosing.
Occurrence of domoic acid in washington state razor clams (Siliqua patula) during 1991‐1993
Authors: Wekell John C. , Gauglitz Erich J. , Bamett Harold J. , Hatfield Christine L , Simons Doug , Ayres Daniel
Published: October 2006

The presence of domoic acid in aquatic species was reported for the first time in the United States in the late summer of 1991 in Monterey Bay, California. By October of 1991, domoic acid was found in razor clams (Siliqua patula) and in the viscera of Dunseness crab (Cancer magister) along the coasts of Washington and Oregon. In response to this outbreak, the National Marine Fisheries Service, in cooperation with the Washington State Department of Fisheries began analysis of Washington State razor clams for the period from November 1991 to June 1993. This survey indicated that domoic acid levels in the edible portion of the razor clams peaked in December of 1991 (average of all Washington state coastal sites: 106 ppm) and followed a slow decline to the present day low levels (<5 ppm). Sixteen months after the maximum level, domoic acid has not completely disappeared from the razor clams from the Washington State beaches. Unlike mussels (Mytilus edulis), where the toxin is found only in the viscera, domoic acid distributes itself throughout the various body parts of the razor clam. The highest concentration occurs in the foot or “disser” and the lowest in the siphon or “neck.” The concentration of domoic acid in the razor clam foot reached a high of 230 ppm. © 1994 Wiley‐Liss, Inc.
Is the A‐ring lactone of brevetoxin PbTX‐3 required for sodium channel orphan receptor binding and activity?
Authors: Baden Daniel G. , Rein Kathleen S. , Gawley Robert E. , Jeglitsch Gerhard , Adams David J.
Published: October 2006

Brevetoxin PbTx‐3 and non‐toxic derivative 4 were investisated for their abilities to bind to the specific brevetoxin receptor site on rat brain synaptosomes and to modulate the normal function of voltase‐sated sodium channels as determined by patch clampins of cultured neurons. Compounds 4 and 5 are produced from PbTx‐3 by opening of the A‐ring lactone to the saturated and unsaturated diols using sodium borohydride in ethanol. Natural PbTx‐3 exhibited tighter binding to rat brain synaptosomes by at least 3 orders of magnitude as determined by competitive radioligand binding experiments, and was also more effective at activating voltage‐gated channels. Patch clamping revealed the 3 orders of magnitude greater potency of PbTx‐3 toxin over 5, although each produced delayed sodium channel opening and a pronounced delay in inactivation. Conformational modeling of the Brevetoxin B backbone indicates that the two molecules are identical except for the region of the A‐Ring lactone. Thus, we conclude that the brevetoxin PbTx‐3 backbone requires electrophilic functionality in the region of the lactone in PbTx‐3, and that opening of the ring in 5 is sufficient to substantially reduce both binding and activity. copy; 1994 Wiley‐Liss, Inc.
Kainic acid and 1′‐hydroxykainic acid from palmariales
Authors: Ramsey Una P. , Bird Carolyn J. , Shacklock Peter F. , Laycock Maurice V. , Wright Jeffrey L. C.
Published: October 2006

The distribution of kainic acid among various red algae was investigated. Analysis of free amino acids from different populations of Palmaria palmata showed that some were unable to accumulate kainic acid to detectable concentrations, whereas in two dwarf mutants it was a major component of the free amino acid composition. The amino acid profiles were also examined for unknown amino acids in the search for possible intermediates in kainic acid biosynthesis. The only unknown amino acid present in P. palmata extracts was isolated and identified by NMR spectroscopy as 1′‐hydroxykainic acid. This compound was found in all samples that contained kainic acid. To investigate the effect of growth conditions on kainic acid production different strains of P. palmata were grown at 5, 10, and 15°C with or without added nitrate. No effect on production was observed, suggesting that the growth conditions in these experiments do not affect the level of gene expression in the pathway of kainic acid biosynthesis. Furthermore, changing the growth conditions did not induce synthesis of kainic acid in the non‐producing strains of Palmariales. © 1994 wiley‐Liss, Inc.
Lung tumor induction in A/J mice and clastogenic effects in CD‐1 mice of the sequence‐selective DNA alkylating agents (+)‐cc‐1065 and (−)‐cc‐1065
Authors: Linseman Daniel A. , Branstetter Daniel G. , Yu Roger L. , Aaron C. S.
Published: October 2006

The in vivo genotoxic effects of the antitumor antibiotic, (−)‐CC‐1065, and its unnatural enantiomer, (−)‐CC‐1065, were investigated in two mouse models. These two compounds alkylate AT‐rich regions of double stranded DNA with distinct sequence selectivities.

(+)‐CC‐1065 dose‐dependently increased the chromosomal aberration frequency in bone marrow cells of CD‐1 mice from 1.2 ± 0.8% in vehicle control animals to 5.0 ± 1.2%, 11.4 ± 3.9%, and 20.6 ± 2.3% 24 hours following single intravenous doses of 2, 4, and 8 μg/kg, respectively. (−)CC‐1065 was significantly less potent with a maximal response at 8 μg/kg approximately one‐third of that observed for (+)‐CC‐1065.

(+)‐CC‐1065 induced a significant (P ± 0.05), three‐fold increase in the number of lung tumors/mouse in strain A/J mice from 0.27 ± 0.15 for vehicle control animals to 0.83 ± 0.15 24 weeks following a single intravenous dose of 8 μs/kg. This effect was paralleled by corresponding threefold increases in the percentage of mice with tumors and the percentage of mice with multiple tumors, compared to vehicle controls. (−)‐CC‐1065 at 8 μg/kg induced 0.67 ± 0.15 tumors/mouse and resulted in slightly smaller increases in the tumor incidence and multiple tumor incidence, compared to (+)‐CC‐1065.

The above results demonstrate that single intravenous doses of (+)‐CC‐1065 and (−)‐CC‐1065 which cause chromosomal damage in CD‐1 mice also induce an increased incidence of lung tumors in A/J mice. (+)‐CC‐1065 may have a slightly greater genotoxic potential in vivo than its unnatural enantiomer. This may be attributable to differences in the DNA binding sequence selectivities of the two compounds. Furthermore, when compared on a μ‐moles/kg basis, (+)‐CC‐1065 is > 7,000 × more potent than N‐ethyl‐N‐nitrosourea at inducing a similar tumorigenic response in the A/J mouse lung tumor bioassay. © 1995 Wiley‐Liss, Inc.