bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurements of Body Composition by Dual‐Energy X‐ray Absorptiometry Improve Prediction of Energy Expenditure
Authors: KISTORP CAROLINE NERVIL , TOUBRO SØREN , ASTRUP ARNE , SVENDSEN OLE LANDER
Published: July 2010

Abstract: The prediction of energy expenditure by dual‐energy X‐ray absorptiometry (DXA) and bioimpedance analysis (BIA) was assessed in 35 healthy individuals of both sexes, with a mean body mass index (BMI) of 23.8 kg/m2 (range 18–33.8), and mean age of 30 years (22–40). Energy expenditure (EE) was measured under standard conditions in a respiration chamber, the total and regional body composition by DXA, and total body composition by BIA. When body composition was measured by BIA, 88.5% of the variation in 24‐h EE was explained by lean body mass (LBM); this figure was increased by DXA, where total lean tissue mass (LTM) and total fat tissue mass (FTM) could account for 91.5% of the variation. Also, the prediction of resting energy expenditure (REE) was improved by DXA, from 88.1% to 89.8% (LBM vs. LTM, FTM). Measurements of regional body composition showed that trunk LTM was significantly superior as a predictor, especially of REE and sleeping EE (EE sleep), compared to the peripheral LTM; thus, the predictions of REE were 83% vs. 87% (peripheral vs. trunk), respectively; and the predictions of EE sleep were 83% vs. 89% (peripheral vs. trunk), respectively. Therefore, body composition measurements by DXA improved the prediction of EE. Trunk LTM was a superior predictor, especially of REE and EE sleep, compared to peripheral LTM. In conclusion, the present results suggest that measuring total and regional body composition by DXA can somewhat improve the prediction of EE.
Of Mermaids and Mountains: Three Decades of Prompt Activation in Vivo
Authors: MORGAN W. D.
Published: July 2010

Abstract: During 1966 to 1972, several laboratories demonstrated the feasibility of measuring the major body elements H, N, Ca, and Cl by prompt gamma in vivo neutron activation analysis (PGIVNA). The MERMAID facility in Birmingham, England used a cyclotron‐produced pulsed neutron beam, but other groups in the United Kingdom, United States, Canada, and New Zealand subsequently developed systems based on radioisotope neutron sources that could measure body nitrogen with a precision of a margin of error of a few percentage points. The accuracy of N measurement was greatly enhanced by Vartsky's internal standardization, using prompt‐gamma H as the marker and total body hydrogen (based on total body water and skinfolds) as the reference. Chlorine and extracellular water volume were used in a similar way by the Swansea group to calibrate the prompt‐gamma analysis of total body calcium. The PGIVNA technique is most valuable in assessing nutritional status, particularly in relation to body protein.
Gamma Ray Nuclear Resonance Absorption: An Alternative Method for in Vivo Body Composition Studies
Authors: VARTSKY D. , GOLDBERG M. B. , BAR D. , GOLDSCHMIDT A. , FELDMAN G. , SAYAG E. , KATZ D. , STRONACH I. M. , STARK J. W. , PRESTWICH W. V. , McNEILL F. E. , CHETTLE D. R.
Published: July 2010

Abstract: We have evaluated gamma ray nuclear resonance absorption (γ‐NRA) on nitrogen, a mature technology proposed and developed by Soreq NRC for detecting explosives, as an alternative to neutron activation for in vivo assaying of body nitrogen. The principles of the γ‐NRA method are outlined, and a test facility constructed at McMaster University's Accelerator Laboratory is described. The results of a feasibility study recently performed there on phantoms and animal tissue are presented and discussed. γ‐NRA is a full imaging technique that essentially constitutes element‐specific absorptiometry‐i.e., it can generate projections of the mass distribution for a specific element, along with a conventional radiograph of the patient. From the transmission profile of an individual scanned by 9.17 MeV gamma rays, local or whole body nitrogen content can be determined via the resonant attenuation undergone when the beam encounters regions of nitrogen concentration. The advantages of γ‐NRA over neutron activation are (a) radiation doses delivered to the body are at least one order of magnitude lower, thus allowing repeated measurements on individual patients and also rendering the method ethically acceptable for application to children; (b) γ‐NRA is inherently free from uncertainties related to nonuniform distributions of the element in question within the body; (c) it is applicable to patients of varying size and shape; and (d) it yields both nitrogen images and conventional radiographic images of the body.
Changes in Body Fluids during Endurance Rowing Training
Authors: JÜRIMÄE JAAK , JÜRIMÄE TOIVO , PIHL EVE
Published: July 2010

Abstract: The aim of this study was to investigate the influence of long‐lasting, extensive rowing training on body fluids in 12 experienced rowers (23.3 ± 6.3 years, 188.7 ± 5.9 cm, 82.0 ± 10.8 kg, body mass index [BMI] 23.7 ± 2.1). All rowers had a light traditional breakfast about 3 h before the training. The subjects rowed 2 h 17 min and covered 22.6 ± 2.5 km. Before and immediately after the training session and after 30, 60, and 120 min of recovery, body fluid balance was measured using a multiple‐frequency impedance device (Multiscan 5000, Bodystat Ltd., UK). Body resistance was measured at the right side of the body. Extracellular (ECW), intracellular (ICW), and total (TBW) body water were measured at 5, 200, and 50 kHz, respectively. Blood hemoglobin (Hgb) and hemotocrit (Hct) were measured, and changes in blood volume (BV), plasma volume (PV), and cell volume (CV) were measured according to Dill and Costill (1974). The body weight of the rowers decreased significantly (p < 0.05) from 82.0 ± 10.8 kg to 80.6 ± 11.2 kg during the endurance training. There were no significant changes in TBW immediately after the training session. Significant changes in the content of TBW occurred during the first 30 min of recovery (48.7 ± 4.4 to 47.9 ± 4.1; p < 0.05). The amount of ECW also decreased significantly during the first 30 min of recovery (23.3 ± 2.0 to 22.7 ± 1.91; p < 0.05). There were no significant changes in the balance of ECW. BV decreased during the training session by 2.5 ± 5.2% (p < 0.05). There were significant relationships (p < 0.05) between the covered distance and the following parameters after the training session: body weight (r=−0.75), TBW (r=−0.75), and ECW (r=−0.83). Changes in the blood parameters did not correlate significantly with changes in body fluids and training volume. It was concluded that extensive rowing training significantly changed the balance of body fluids in rowers.
A Prospective Study of Body Composition Changes in Children with Cystic Fibrosis
Authors: STETTLER NICOLAS , KAWACHAK DEBORAH A. , BOYLE, LISA L. , PROPERT KATHLEEN J. , SCANLIN THOMAS F. , STALLINGS VIRGINIA A. , ZEMELA BABETTE S.
Published: July 2010

Abstract: Recent cross‐sectional studies of children with cystic fibrosis (CF) have shown an improvement in their growth with improved nutritional status, but there are only a few longitudinal studies in this population. A four‐year prospective study was conducted in 25 children with CF and 26 controls, ages 5 to 10 years at baseline, to describe changes in body composition using three independent methods of assessment: skinfold thickness, total body water by deuterium dilution, and total body electrical conductivity (TOBEC). The statural growth of the boys with CF was slower than that of the control boys. Using different methods, the fat‐free mass and fat‐mass increases were shown to be slower in boys with CF than in controls. These differences were less significant in girls. Despite comprehensive care, the growth of boys with CF may still not be optimal, as observed longitudinally.
Fat Distribution and Health in Obesity
Authors: ALBU JEANINE B. , KOVERA ALBERT J. , JOHNSON JULIA A.
Published: July 2010

Abstract: Although independent associations of visceral fat with the insulin resistance syndrome were previously reported in obese women, the importance of truncal subcutaneous fat in this syndrome is controversial. The method by which the various fat depots are measured may be the reason for the underlying controversy. In the past five years, we have used various methods to measure visceral versus subcutaneous fat distribution in Caucasian (C) and African‐ American (AA) women and have related it to insulin sensitivity (SI) and to blood lipids, particularly fasting serum triglyceride levels (TG). Elevated TG levels in obese women were best predicted by an increased amount of visceral fat, whereas the amounts of truncal and peripheral subcutaneous fat did not have an impact on them. These results were confirmed, regardless of the method used to measure the fat depots. Insulin resistance (low SI) in obese women was predicted by both an increase of visceral and of upper‐body (truncal) subcutaneous fat. However, measurements of the entire visceral and truncal subcutaneous fat volumes may be needed to confirm this latter association.
Longitudinal Assessment of Intra‐abdominal Fat in Postmenopausal Women
Authors: HOOVER LORETTA W. , BOOTEC EVAN J.
Published: July 2010

Abstract: Longitudinal changes in intra‐abdominal (IA) fat and total body fat were assessed in three healthy postmenopausal Caucasian women receiving hormone replacement therapy (HRT) during a seven‐year follow‐up study. Measurements were made using dual‐energy X‐ray absorptiometry, anthropometry, and magnetic resonance images. Changes in intra‐abdominal fat were examined in relation to different patterns of weight modification. The weight‐stable woman had the lowest percent body fat and IA fat at all examinations, with a slight decrease in IA fat at follow‐up. The person with a gradual gain in weight of 1.9 kg experienced small increases in body fat and IA fat. The weight‐cycling woman had the highest weight, percent body fat, and IA fat area at all examinations. The amounts of IA fat and percent body fat fluctuated with body weight fluctuations. Together with other findings, our results suggest that lean, weight‐stable individuals receiving HRT can maintain a low level of IA fat, whereas those experiencing weight gains or regaining lost weight have increases in IA fat.
Body Composition Assessed by Neutron Activation Analysis in Dialysis Patients
Authors: STALL SHARON , DEVITA MARIA V. , GINSBERG NANCY S. , FRUMKIN DALIA , LYNN ROBERT I. , MICHELIS MICHAEL F.
Published: July 2010

Abstract: Malnutrition is prevalent in end‐stage renal disease (ESRD) patients treated with hemodialysis (HD) and peritoneal dialysis (PD). In addition, there is increased incidence of morbidity in this group. Evaluation of nutritional status is important. Application of body composition in the ESRD population to evaluate body compartments and to assess nutritional health has become more common in clinical practice. Neutron activation analysis (NAA) may provide data on metabolically active tissue by quantification of total body potassium (TBK) for body cell mass and assessment of protein by total body nitrogen (TBN). This method may be able to detect changes in body composition before clinical signs of malnutrition are apparent. Ten HD (5 male and 5 female) and 10 PD patients (7 male and 3 female) were evaluated by NAA, TBK, and isotope dilution. Female PD patients had an increased total body water (TBW) and increased intracellular water compared to HD females. Albumin was lower in PD women. There was no significant difference between PD men and laboratory controls in TBW, extracellular water, and TBN. The clinical application of body composition methods for evaluation of dialysis patients by serial assessment and for development of a bedside tool needs further study.
Bone Mass and Gastrointestinal Disease
Authors: SEMRAD CAROL E.
Published: July 2010

Abstract: Several gastrointestinal and liver diseases impair the absorption of calcium, phosphate, and/or vitamin D, and are associated with an increased incidence of bone disease. Changes in bone mineral density (BMD) using dual‐energy X‐ray absorptiomety (DXA) have been best studied in the malabsorptive disorder, celiac disease. Celiac disease is an inflammatory condition of the small intestine triggered by ingesting gluten present in wheat, rye, or barley. Chronic inflammation leads to intestinal atrophy and nutrient malabsorption. The disease affects the proximal small bowel; the site where calcium is best absorbed. About 70% of adults with celiac disease have abnormally low BMD values. Treatment with a gluten‐free diet increases BMD, but not to normal values. As celiac disease may not be detected until adult life, the failure to reach normal BMD on a gluten‐free diet can be explained, at least in part, by the failure to reach peak bone mass. All individuals with malabsorptive disorders should be screened for secondary bone disease. The development of easier and less expensive methods to assess BMD will facilitate screening those at risk for bone disease.
Sphingosine 1‐Phosphate: A Ligand for the EDG‐1 Family of G‐Protein‐Coupled Receptors
Authors: SPIEGEL SARAH
Published: July 2010

Abstract: Ample evidence indicates that sphingosine‐1‐phosphate (SPP) can serve as an intracellular second messenger regulating calcium mobilization, cell growth, and survival. Moreover, the dynamic balance between levels of the sphingolipids metabolites, ceramide, and SPP, and consequent regulation of opposing signaling pathways, is an important factor that determines whether a cell survives or dies. This ceramide/SPP rheostat is an evolutionarily conserved stress regulatory mechanism influencing growth and survival of yeast. In addition, SPP also has been identified as the ligand for the G‐protein‐coupled receptors EDG‐1, ‐3, ‐5, and ‐6. Binding of SPP to EDG‐1 regulates chemotaxis and in vitro angiogenesis of endothelial cells, whereas EDG‐5, and possibly EDG‐3, are likely the cell surface receptors responsible for cell rounding and neurite retractions induced by SPP. Hence, the studies identify a family of highly specific SPP receptors that are capable of mediating different biological responses. Thus, it is suggested that SPP is a prototype for a novel class of lipid mediators that act both extracellularly as ligands for cell surface receptors and intracellularly as second messengers. Recently, sphingosine kinase was purified to homogeneity and the first mammalian sphingosine kinase, the enzyme responsible for the formation of SPP, was cloned. The studies should provide the necessary tools to develop insight into the biological roles of this important bioactive sphingolipid.
The Role of De Novo Ceramide Synthesis in Chemotherapy‐Induced Apoptosis
Authors: PERRY DAVID K.
Published: July 2010

Abstract: The de novo pathway of sphingolipid synthesis has been implicated as an alternative to sphingomyelinase activation in generating an apoptotic response through ceramide. A chemotherapy agent was used to activate this pathway in a human T‐cell line in order to investigate the role of de novo ceramide synthesis in apoptosis. In data obtained from intact cell radiolabeling studies, it was observed that the first and rate‐limiting enzyme in de novo synthesis, serine palmitoyltransferase, is activated and controls the production of ceramide through this pathway. Furthermore, using agents that selectively inhibit ceramide production by this pathway, partial protection from cell death was observed that was independent of caspase activation. These results reveal that serine palmitoyltransferase, an enzyme that controls sphingolipid synthesis for housekeeping functions, is activated during apoptosis and serves to mediate events in this process.
Phospholipid Growth Factors and Corneal Wound Healing
Authors: WATSKY MITCHELL A. , GRIFFITH MAY , WANG DE‐AN , TIGYI GABOR J.
Published: July 2010

Abstract: In many tissue types, wound healing involves cell division and migration over and into the wound area to cover and remodel the wound. LPA and other members of the phospholipid lipid growth factor (PLGF) family stimulate many of the activities involved in wound healing. In the rabbit cornea, we have found that keratocytes from wounded corneas have a volume‐activated Cl− current activated by LPA and alkenyl‐LPA. This current is minimally activated by cyclic PA and SPC, and is not activated by LPA in cells from uninjured corneas. Biochemical examination of PLGFs in aqueous humor and lacrimal fluid before and after wounding identified LPA, alkenyl‐GP, PA, and lyso PS, with elevated PLGF activity after wounding. In recent experiments examining human corneal cell lines and cultured cells using RT‐PCR, we found mRNA for EDG receptors 1–5, with an apparent increase in EDG‐3, ‐4, and ‐5 following brief SDS application to cell lines, and EDG receptors 2–5 induction in late‐passage human corneal epithelial cells. This work points to a significant role for PLGFs in the corneal wound‐healing process.
Loss of Heterozygosity at the ACTBP2 Locus in Lung Cancer Detected on Elchrom Precast Spreadex Gels
Authors: KOZULIC MIRJANA , CHEN XU QI , BONILLA FELIX , SILVA JOSE
Published: July 2010

Abstract: One of the most important goals in the continuous struggle against cancer is early detection of the disease by a simple method that can be used in routine laboratory practice. According to several recent reports, early detection may be achieved by monitoring alterations at several microsatellite loci containing tri‐ and tetranucleotide repeats. The method relies on comparison of the intensity of allele bands in cancer tissue, plasma, and lymphocytes of a patient. Microsatellite instability is typically detected by labeling the DNA with a radioactive probe or a fluorescent dye followed by electrophoresis on 20–40‐cm‐long denaturing polyacrylamide gels. In this study, we show that loss of heterozygosity at the ACTBP2 locus in lung cancer patients can be detected using the Elchrom electrophoresis system and just 4‐cm‐long precast Spreadex gels.
The Relationship Between the Theory of Evolution and the Social Sciences, Particularly Psychology
Authors: HASS R. GLEN , CHAUDHARY NEIL , KLEYMAN EMILY , NUSSBAUM ALEXANDER , PULIZZI ALLISON , TISON JULIE
Published: July 2010

Abstract:The application of the theory of evolution to human social behavior has, along with some illumination, produced friction that occasionally bursts into flame. In this paper we will examine the relationship between the theory of evolution and the social sciences, psychology in particular. We will identify some of the sources of friction between proponents and opponents of applying evolutionary theory to the social sciences, and we will suggest that listening carefully to both sides in the debate points the way to an enriched understanding of human social behavior.
The Elements of a Scientific Theory of Self‐Deception
Authors: TRIVERS ROBERT
Published: July 2010

Abstract:An evolutionary theory of self‐deception‐the active misrepresentation of reality to the conscious mind‐suggests that there may be multiple sources of self‐deception in our own species, with important interactions between them. Self‐deception (along with internal conflict and fragmentation) may serve to improve deception of others; this may include denial of ongoing deception, self‐inflation, ego‐biased social theory, false narratives of intention, and a conscious mind that operates via denial and projection to create a self‐serving world. Self‐deception may also result from internal representations of the voices of significant others, including parents, and may come from internal genetic conflict, the most important for our species arising from differentially imprinted maternal and paternal genes. Selection also favors suppressing negative phenotypic traits. Finally, a positive form of self‐deception may serve to orient the organism favorably toward the future. Self‐deception can be analyzed in groups and is done so here with special attention to its costs.
The Evolution of Moral Dispositions in the Human Species
Authors: KREBS DENNIS L.
Published: July 2010

Abstract:Kohlberg's model of moral development is viewed from the perspective of evolutionary biology. Moral judgments defining Kohlberg's stages of moral development are seen as manifestations of structures evolved to uphold systems of cooperation. Game theory research on adaptive strategies of cooperation supports the conclusion that humans inherit dispositions to uphold the systems of cooperation implicit in the first three stages in Kohlberg's sequence, but not the systems of cooperation implicit in the highest stages. The empirical evidence on real‐life morality is more consistent with a biological model of ontogenesis than is the model espoused by Kohlbergians. Although people occasionally make moral judgments in their everyday lives to reveal their solutions to moral dilemmas, as Kohlberg's model assumes, they more often make moral decisions that advance their adaptive interests.
Female Reproductive Strategies as Social Organizers
Authors: PRASCHNIK‐BUCHMAN DIANA
Published: July 2010

Abstract: When male philoparty is linked to patriarchy, it is often assumed that female reproductive strategies are secondary to male reproductive strategies. By comparing the social structures of chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) with those of other non‐human primates, I argue that female reproductive strategies can be viewed as primary principles of social organization, including the establishment of patriarchies through differential investment in offspring. Emphasis on the contributions of female reproductive strategies may lead to a different picture of the evolution of primate social organization.
Resisting Biology: The Unpopularity of a Gene's‐Eye View
Authors: TERLEPH THOMAS A.
Published: July 2010

Abstract: David Haig's intragenomic conflict theory concerning the possible evolutionary origins of genomic imprinting is discussed. It is suggested that a useful way in which one might represent Haig's theory to a popular audience would be by emphasizing a gene's eye viewpoint. In doing so, an author may help to dispel common misconceptions about evolution and natural selection, misconceptions which arise in part from an overemphasis on the individual, rather than the gene, when discussing natural selection. Although it is possible to view either the gene or the individual as a unit of natural selection, our own proclivity towards overemphasizing the role of individuals in evolution is seen as a common impediment to a more complete understanding of both natural selection, as well as the philosophical implications arising from a gene's eye view of evolutionary theory.
Fibroblast Responses to Exogenous and Autocrine Growth Factors Relevant to Tissue Repair: The Effect of Aging
Authors: KLETSAS DIMITRIS , PRATSINIS HARRIS , ZERVOLEA IRENE , HANDRIS PANAGIOTIS , SEVASLIDOU ELENI , OTTAVIANI ENZO , STATHAKOS DIMITRI
Published: July 2010

Abstract: The aging process is often associated with impaired wound healing, but the cellular and molecular mechanisms implicated are not completely understood. Accordingly, we have investigated the response of human fibroblasts from donors of various ages to platelet‐derived and autocrine growth factors, in terms of mitogenicity as well as extracellular matrix synthesis and degradation. Our data indicate that fibroblast responses persist during aging, suggesting the involvement of systemic factors in the regulation of the healing process. In this context, we have found that neutral endopeptidase‐24.11, a metalloproteinase controlling the action of neuroendocrine peptides and also of immunocyte chemotaxis, is overexpressed during aging. Finally, the connection between these data and those from in vitro aging studies is discussed.
Role of Mitochondrial DNA Mutations in Disease and Aging
Authors: COTTRELL D. A. , BLAKELY E. L. , BORTHWICK G. M. , JOHNSON M. A. , TAYLOR G. A. , BRIERLEY E. J. , INCE P. G. , TURNBULL D. M.
Published: July 2010

Abstract: Since Harman in 1972 first proposed a role in the process of aging for the mitochondrial genome, a wealth of evidence has been accumulated to support this theory. We discuss the hereditary mitochondrial DNA disorders, which we believe may give insight into both normal aging and neurodegenerative conditions. We then review the evidence for the role of mitochondrial DNA mutations in both aging and age‐related disorders and also discuss new approaches for investigating the mitochondrial genome at a single cell level, by observing the activity of the mitochondrial enzyme cytochrome c oxidase.
Molecular Genetics of Hereditary Nonpolyposis Colorectal Cancer
Authors: BOLAND C. RICHARD
Published: July 2010

Abstract: The initial paradigm developed for colorectal carcinogenesis was derived from the observation that these tumors suffer a large number of chromosomal losses. This phenomenon results from unbalanced mitoses, and to date there is no clear explanation for this type of genomic instability. In 1993, a second type of genomic instability was detected and linked to 12–15% of sporadic tumors, as well as 90% or more of the colon cancers in hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC tumors are typically diploid and do not have the inactivating mutations at the tumor suppressor genes commonly found in the other cancers. These tumors were found because they have a very large number (perhaps in excess of 105) of insertion or deletion mutations at microsatellite sequences; as a result, this has been termed microsatellite instability (MSI). The majority of HNPCC families can be linked to germline mutations in the DNA mismatch repair (MMR) genes hMSH2 or hMLH1. Germline mutations in hMSH6 and hPMS2 in HNPCC families are much less common. HNPCC tumors develop through the accumulation of mutations at genes that control cellular growth, and these genes are not the same as those recognized in the initial pathway outlined by Vogelstein et al.1 The genetic targets of MSI all contain repetitive sequences in coding regions that are unstable when the DNA MMR system is inoperative. Certain pathological features have been identified that suggest that colon cancers have developed in the setting of defective DNA MMR.
Use of Representational Difference Analysis and cDNA Arrays for Transcriptional Profiling of Tumor Tissue
Authors: FROHME MARCUS , SCHARM BURKHARD , DELIUS HAJO , KNECHT RAINALD , HOHEISEL JÖRG D.
Published: July 2010

Abstract: Representational difference analysis of cDNA (cDNA‐RDA) was used for a comparison of the global transcript level of tumor of the larynx and the corresponding normal epithelial tissue toward the end of detecting differentially expressed genes. Overall, some 130 gene fragments were identified. By sequence analysis and homology comparison, they could be put into several groups related to (potential) functions. Apart from genes whose overexpression was most likely a result of tumor growth or dedifferentiation of epithelial tissue, a lot of genes were isolated that play major roles in signal transduction pathways or apoptosis or act as oncogenes or tumor suppressor genes, in addition to new, entirely unknown genes. Moreover, some cDNAs of known genes were identified that derived from unconventional splicing activity or other transcript modifications. All identified fragments were arrayed on solid support and used for reverse Northern blot analyses. The use of preselected RDA fragments as targets in array‐based profiling experiments circumvents many of the problems encountered when dealing with large clone libraries.
p53: A Potential Target Antigen for Immunotherapy of Cancer
Authors: OFFRINGA RIENK , VIERBOOM MICHEL P. M. , VAN DER BURG SJOERD H. , ERDILE LORNE , MELIEF CORNELIS J. M.
Published: July 2010

Abstract: Approximately 50% of all human malignancies exhibit mutation and aberrant expression of p53, making this protein an interesting candidate target for immunotherapy of cancer. Mutations in p53 are highly diverse. Therefore, targeting of determinants within the wild‐type p53 sequence appears most practical. Despite the fact that p53 is ubiquitously expressed, adoptive immunotherapy of tumor‐bearing mice with p53‐specific cytotoxic T lymphocytes (CTL) results in eradication of p53‐overexpressing tumors in the absence of immunopathological damage to normal tissues. These CTL also eliminate tumors that do not show greatly enhanced expression of p53, indicating that the sensitivity of these tumors for p53‐specific CTL is determined by the efficiency by which p53‐derived peptides are processed into class I MHC, rather than by the steady state levels of p53. Of note, although p53‐specific CTL can readily be isolated from p53−/− mice, tolerance for this self antigen may prevent induction of similarly effective CTL in p53+/+ subjects. The T helper (Th) branch of the p53‐specific immune response does not seem to be profoundly affected by tolerance. In addition, more and more evidence is obtained for the pivotal role of tumor‐specific Th cells in the induction and effector phases of the antitumor response, also against tumors that lack class II MHC expression. The efficacy of Th cells, specific for a recently identified class II MHC‐restricted p53 peptide, against p53‐overexpressing tumors is currently being investigated. In addition, natural and induced Th responses are analyzed both in a murine tumor model and in a phase I clinical trial involving p53‐specific vaccination of colon cancer patients.
Molecular Effects of the Psychotropic NMDA Receptor Antagonist MK‐801 in the Rat Entorhinal Cortex: Increases in AP‐1 DNA Binding Activity and Expression of Fos and Jun Family Members
Authors: KONTKANEN OUTI , LAKSO MERJA , KOPONEN EIJA , WONG GARRY , CASTRÉN EERO
Published: July 2010

Abstract: Noncompetitive NMDA receptor antagonists such as phencyclidine and MK‐801 produce psychotropic symptoms that closely resemble schizophrenic psychosis and induce the expression of immediate early genes in limbic cortical areas. We are concentrating on analyzing molecular and physiological effects that these drugs produce in the entorhinal cortex and on the potential connection between these effects and the psychotic symptoms. We show here that MK‐801 increases the DNA binding activity of the activator protein‐1 (AP‐1) complex in the entorhinal cortex. We also observed increased expression of mRNAs for Fos and Jun transcription factor family members c‐Fos, FosB, Fra‐2, and JunB, as well as Fos family proteins in the entorhinal cortex after MK‐801 administration. This suggests that the activated AP‐1 complex consists of these transcription factors. Genes regulated by the AP‐1 complex in the entorhinal cortex might be involved in the pathophysiology of psychotic behavior and are potential targets for new antipsychotic drugs.
Properties of Entorhinal Cortex Projection Cells to the Hippocampal Formation
Authors: HEINEMANN U. , SCHMITZ D. , EDER C. , GLOVELI T.
Published: July 2010

Abstract: There are multiple connections from the entorhinal cortex (EC) to the hippocampus that carry the information from the EC to the hippocampus. Layer II cells of the medial EC innervating the dentate gyrus (DG)‐molecular layer possess K+‐outward currents and inward rectifier currents that are potentially modulated by changes in intracellular second messengers. Layer II cells responded to synaptic stimulation with a rather flat input‐output curve, and much stronger stimuli are required to generate action potentials in these neurons than in EC layer III cells. During repetitive stimulation at frequencies of 10 Hz and more, EC layer II cells respond with increased likelihood to generate action potentials. Two different NMDA conductances can be demonstrated in these neurons. A slow, less Mg, less voltage‐dependent component is responsible for the transient depolarization between the fast and slow IPSP. A second group of neurons also projects to the DG. These are either pyramidal or nonpyramidal cells in the deep layers of the EC. At least part of these neurons also possess rhythmogenic properties. In contrast to layer II cells, layer III neurons have a steep input‐output curve and show during repetitive synaptic activation a tendency to repolarize and to display long‐lasting inhibitions dependent on GABAB‐, atropine‐, and naloxone‐sensitive components. As a consequence, they are readily activated during low frequency stimulation, but project only a few action potentials to area CA1 initially during higher (more than 10 Hz) frequency synaptic stimulation.
Amygdalo‐Entorhinal Inputs to the Hippocampal Formation in Relation to Schizophrenia
Authors: BENES FRANCINE M. , BERRETTA SABINA
Published: July 2010

Abstract: This chapter reviews recent postmortem studies of schizophrenic brain and discusses the potential role of the amygdala in the induction of hippocampal abnormalities in this disorder. Based on available evidence, sectors CA4, CA3, and CA2, but not CA1, show preferential changes in schizophrenic subjects, although the most pronounced changes have been found in CA3 and CA2. It seems likely that the amygdala would contribute in some way to the induction of abnormalities along the trisynaptic pathway via its direct input to sectors CA3 and CA2, as well as an indirect one that involves the entorhinal cortex and its perforant path projection to the area dentata. The postmortem findings reported to date have been integrated into a working model in which decreases of inhibitory GABAergic modulation are invoked to explain the observation from a recent PET scan study (Heckers et al., 1999) that baseline metabolic activity in the hippocampus of schizophrenics is increased. In addition, however, the apparent inability of schizophrenics to increase metabolic activity in the hippocampus when challenged with a memory retrieval task may reflect a disturbance of disinhibitory modulation postulated herein to occur in sector CA3, a key relay point along the trisynaptic pathway. Overall, it seems plausible that an increase of excitatory activity entering the hippocampus from the basolateral complex via both direct and indirect pathways may make a significant contribution to the pathophysiology of schizophrenia.
Neurons in Layer III of the Entorhinal Cortex: A Role in Epileptogenesis and Epilepsy?
Authors: SCHWARCZ ROBERT , EID TORE , DU FU
Published: July 2010

Abstract: A preferential lesion of neurons in layer III of the entorhinal cortex (EC) is often observed in patients suffering from temporal lobe epilepsy and in several animal models of the disease. This lesion is duplicated in rats by a focal, intra‐entorhinal injection of the “indirect” excitotoxin aminooxyacetic acid (AOAA), providing a model that can be used to study the mechanisms underlying seizure‐induced cell death and epilepsy. Doomed neurons in the EC and in several associated limbic structures show pathological changes within hours after the AOAA injection, but GABAergic neurons in layer III of the EC are quite resistant. This pattern of neuron loss eventually results in hippocampal and entorhinal hyperexcitability. Notably, the seizure‐induced death of layer III neurons in the EC can be attenuated by eliminating the prominent excitatory input from the presubiculum. Taken together, these results suggest opportunities to target parahippocampal structures for the treatment of temporal lobe epilepsy.
Morphometric MRI Analysis of the Parahippocampal Region in Temporal Lobe Epilepsy
Authors: BERNASCONI NEDA , BERNASCONI ANDREA , CARAMANOS ZOGRAFOS , ANDERMANN FREDERICK , DUBEAU FRANÇOIS , ARNOLD DOUGLAS L.
Published: July 2010

Abstract: Despite neuropathological and electrophysiological evidence for the involvement of parahippocampal structures in temporal lobe epilepsy (TLE), little attention has been paid to morphometric changes in these structures, and the relation of these changes to TLE. We performed high‐resolution MRI volumetric analysis to examine in vivo the morphology of the parahippocampal region in 20 healthy subjects and 6 TLE patients with MRI evidence of unilateral hippocampal atrophy. In normal controls the standardized volume of the left entorhinal cortex (EC) was 1305 ± 138 mm3 and that of the right EC was 1376 ± 170 mm3; the left perirhinal cortex (PC) was 2900 ± 554 mm3 and the right PC was 2771 ± 486 mm3; the left posterior parahippocampal cortex (PPC) was 2499 ± 583 mm3 and the right PPC was 2234 ± 404 mm3. Using a 2 standard deviation cutoff from the mean of normal controls, we found ipsilateral to the seizure focus: (i) a reduction in the volume of the EC in all patients; (ii) a reduction of the PC in 2/6 (33%) patients; (iii) no reduction in the volume of the PPC in any patient. In 3/6 (50%) of patients, the EC was also abnormally small contralateral to the seizure focus. In patients with unilateral TLE, the EC is the most affected structure within the parahippocampal region. Whether this is due to a primary role of the EC in the genesis of TLE or is the consequence of its pivotal position in the reciprocal flow of information between the hippocampus and the neo‐ and limbic cortices remains to be explored.
An In Situ Experiment of Methane Sequestration as Gas Hydrate, Authigenic Carbonate, and Loss to the Water Column and/or Atmosphere
Authors: KASTNER MIRIAM , CARSON BOBB , BARTLETT DOUGLAS B. , JAEGER JOHN , BIDLE KELLY , JANNASCH HANS
Published: July 2010

Abstract: A one year in situ experiment to quantify the flux of carbon, primarily as methane, from an overpressured thrust fault at the Cascadia convergent margin (ODP Site 892B) is described. Most of the expelled carbon is sequestered in two solid phases, methane hydrate and authigenic carbonates and an unknown portion is lost in the water column and/or atmosphere.14 ages of clam shells from the vicinity of the site suggest active methane venting for at least 21–24 kyrs. The water column chemistry provides information on the potential effects of global warming on rapid massive gas hydrate dissociation and on the effects of microbial oxidation of the released methane on the local oceanic oxygen and CO2 contents. The local and global implications of these processes for the oceanic carbon cycle are being assessed.
Methane Hydrate Estimates from the Chloride and Oxygen Isotopic Anomalies: Examples from the Blake Ridge and Nankai Trough Sediments
Authors: MATSUMOTO RYO
Published: July 2010

Abstract: Oxygen isotopic fractionation between gas hydrate and ambient water is determined as αGH‐IW= 1.0037 at 12–16°C and 31 Mpa, on the basis of direct measurements of gas hydrate‐derived waters and ambient pore waters recovered from the Blake Ridge during ODP Leg 164. Oxygen isotopic anomalies give us the amount of gas hydrate of 7 to 9% (pore filling), which is almost twice as much as estimates from chloride anomalies. The difference is probably due to uncertainties in determining base‐line profiles of the in situ pristine pore waters, and partially due to the effects of selective filtration/adsorption during pore water extraction. Two 250 meter‐deep holes were drilled in the eastern Nankai trough off central Japan at a water depth of 950 m, where strong BSRs occur at about 300 mbsf. Massive hydrates were not recovered during this drilling but a number of soupy horizons suggest the existence of subsurface gas hydrate. Chloride concentration and δ18O of interstitial waters are observed to vary in a remarkable zigzag pattern with spiky anomalies, reflecting hydrate dissociation during core‐recovery and water extraction. The concentration of gas hydrate in sediments is estimated to be about 3–7% with a spiky maximum value of 30% from chloride anomalies and between 5 and 30% from δ18O anomalies. Significant difference in vertical distribution between nearby two holes in Nankai Trough probably reflect heterogeneous fluid migration through particular conduits in an accretionary wedge.
Relation between Gas Hydrate and Physical Properties at the Mallik 2L‐38 Research Well in the Mackenzie Delta
Authors: WINTERS W. J. , DALLIMORE S. R. , COLLETT T. S. , JENNER K. A. , KATSUBE J. T. , CRANSTON R. E. , WRIGHT J. F. , NIXON F. M. , UCHIDA T.
Published: July 2010

Abstract: As part of an interdisciplinary field program, a 1150‐m deep well was drilled in the Canadian Arctic to determine, among other goals, the location, characteristics, and properties of gas hydrate. Numerous physical properties of the host sediment were measured in the laboratory and are presented in relation to the lithology and quantity of in situ gas hydrate. Profiles of measured and derived properties presented from that investigation include: sediment wet bulk density, water content, porosity, grain density, salinity, gas hydrate content (percent occupancy of non‐sediment grain void space), grain size, porosity, and post‐recovery core temperature. The greatest concentration of gas hydrate is located within sand and gravel deposits between 897 and 922 m. Silty sediment between 926 and 952 m contained substantially less, or no, gas hydrate perhaps because of smaller pore size.
The Effect of CO2‐Air Mixture Compositions on the Formation and Dissociation of CO2 Hydrate
Authors: HANEDA HIRONORI , KOMAI TAKESHI , YAMAMOTO YOSHITAKA
Published: July 2010

Abstract: The disposal of carbon dioxide to the marine and sea bed sediments as CO2 gas hydrate is an innovative technique for solving the global environment issue. Experiments on the formation and dissociation of gas hydrate have been carried out using a pressure vessel to investigate the effect of carbon dioxide concentration in the gas phase. From the experiment results, the following are clarified: (1) There is a strong relationship between the partial pressure of carbon dioxide, concentration, and the temperature of formation and dissociation of gas hydrate. Therefore, the use of this relation enables the estimation of equilibrium conditions of the gas mixture. (2) The initial formation rate varies from 0.1 to 0. 5 ml/(min·g). In terms of average values, the initial formation rate increases as the carbon dioxide concentration of the initial gas mixture increases. (3) From the analysis of component gas of gas hydrate and space gas, it can be assumed that nitrogen and oxygen are also incorporated into the hydrate structure cage as guest molecules. Moreover, it can be seen that the carbon dioxide concentration in the initial space gas is higher than that in the space gas at the time of gas hydrate formation. Therefore, this hydrate technology applies to the concentration of carbon dioxide. In future, we will attempt to carry out tests on the formation and dissociation of CO2 hydrate under a low concentration of CO2. Furthermore, we will analyze the structure of gas hydrate using Raman spectroscopy to clarify that nitrogen and oxygen are incorporated into the gas hydrate cage as guest molecules.
Hydrate Plug Computer Tool
Authors: BORTHNE GUNNAR , BLOYS BEN
Published: July 2010

Abstract: Petroleum transportation pipelines are occasionally plugged by gas hydrate. Such plugs can be very costly because of delayed production and complicated removal procedures. The objective of this work was to develop a prototype computer program, with a collection of calculation modules, that could be useful in connection with the removal of hydrate plugs, and that could be extended in future to a more comprehensive tool. The program presently consists of five calculation modules. Most of the focus of this paper will be on the first of these‐a module that can be used to analyze pressure time series to monitor plug dissociation progress.
Gas Hydrates and Offshore Drilling: Predicting the Hydrate Free Zone
Authors: ØSTERGAARD K. K. , TOHIDI B. , DANESH A. , TODD A. C.
Published: July 2010

Abstract: A well‐recognized hazard in offshore drilling is the formation of gas hydrates in the event of a hydrocarbon flow into the well bore from the reservoir (e.g., a kick). This could potentially block the BOP stack, kill lines and chokes, obstruct the movement of the drill string, and cause serious operational and safety concerns. Currently, salts are added to the drilling fluids to inhibit hydrate formation in offshore and arctic drilling. For deep water drilling, even saturated saline solutions may not provide the required protection, unless combined with chemical inhibitors. The reported experimental data on gas hydrate formation in drilling fluids are very limited and in some cases inconsistent. The available predictive methods are generally empirical correlations based on limited data and with limited application. In this presentation, a thermodynamic model capable of predicting the hydrate free zone in the presence of salts (NaCl, KCl, CaCl2, NaBr, Na‐formate, etc.) and chemical inhibitors (methanol, ethanol, ethylene glycol, glycerol, etc.) is presented. The model developed has been employed to predict the hydrate free zone in drilling fluids designed for offshore and deep water applications. The predictions are compared with experimental data and an empirical correlation, demonstrating the reliability of the thermodynamic model.
Calorimetry to Study Metastability of Natural Gas Hydrate at Atmospheric Pressure and Temperatures below 0°C
Authors: LEVIK O. I. , GUDMUNDSSON J. S.
Published: July 2010

Abstract: Natural gas hydrate is metastable when stored at atmospheric pressure and temperatures below 0°C. The hydrate is regarded as metastable since, under these pressure‐temperature conditions, the rate of dissociation is very low. Isothermal calorimetry was used to study the rate of dissociation, which is a measure of the metastability. Low temperatures and large samples improve the stability. The isothermal method is being developed to quantify metastability. Scanning calorimetry was used to determine the hydrate number and amount of free water. In the scanning method, the natural gas hydrate sample was pressurized with methane. The calorimeter was operated below the methane hydrate equilibrium line and above the natural gas hydrate equilibrium line. Prior to analysis, the sample was conditioned in a separate heating‐cooling cycle. This was necessary to eliminate undesirable thermal responses due to desorption as the ice melted. Desorption occurred because the sample was refrigerated (−20°C) under a high natural gas pressure, but analyzed under a relatively low methane pressure. The scanning method is being developed to analyze natural gas hydrate that contains large amounts of free water.
An Engineering Approach to Kinetic Inhibitor Design Using Molecular Dynamics Simulations
Authors: FREER E. M. , SLOAN E. D.
Published: July 2010

Abstract: This paper examines the use of molecular dynamics simulations to predict the performance of kinetic inhibitor structures by simulating adsorption on the sII {111} hydrate growth plane. Inhibitor performance was observed to correlate to subcooling and van der Waals forces for the sample group of kinetic inhibitors used in the molecular dynamics simulations.
Configuration‐Biased Monte Carlo Simulations of Poly(vinylpyrrolidone) at a Gas Hydrate Crystal Surface
Authors: CARVER TIM J. , DREW MICHAEL G.B. , RODGER P. MARK
Published: July 2010

Abstract: In this paper we report the use of Monte Carlo simulation methods to study the properties of both isotactic and atactic PVP near a hydrate surface for polymers with molecular weights up to 12,000 Daltons. Information is presented about the conformation and particle size distribution found for PVP bound to a hydrate surface, and about the adsorption sites and energies involved. These results are found to correlate with the behavior already identified for the vinylpyrrolidone monomer. In particular, the same adsorption sites are evident. In the polymeric case the adsorption of any one unit is less optimal than was found for the monomer, but the trains of adsorbed polymer were found to involve partial occupancy of a succession of monomeric adsorption sites.