bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of the Akt/Glycogen synthase kinase‐3 axis by insulin‐like growth factor‐II via activation of the human insulin receptor isoform‐A
Authors: Scalia Pierluigi , Heart Emma , Comai Lucio , Vigneri Riccardo , Sung Chin K. 
Published: August 2002

AbstractInsulin‐like growth factor II (IGF‐II) plays a key role in mitogenesis during development and tumorigenesis and is believed to exert its mitogenic functions mainly through the IGF‐I receptor. Recently, we identified the insulin receptor isoform A (IRA) as an additional high affinity receptor for IGF‐II in both fetal and cancer cells. Here we investigated the mitogenic signaling of IGF‐II via the Akt/Glycogen synthase kinase 3 (Gsk3) axis employing R‐IRA cells that are IGF‐I receptor null mouse embryonic fibroblasts expressing the human IRA. IGF‐II induced activation of the proto‐oncogenic serine kinase Akt, reaching maximal at 5–10 min. IGF‐II also caused the rapid and sustained deactivation of glycogen synthase kinase 3‐beta (Gsk3β), reaching maximal at 1–3 min, shortly preceding, therefore, maximal activation of Akt. Under our conditions, IGF‐II and insulin induced 70–80% inhibition of Gsk3βactivity. In these cells IGF‐II also deactivated Gsk3α although less effectively than Gsk3β. In parallel experiments, we found that IGF‐II induced transient activation of extracellular‐signal‐regulated kinases (Erk) reaching maximal at 5–10 min and decreasing thereafter. Time courses and potencies of regulation of both mitogenic pathways (Akt/Gsk3β and Erk) by IGF‐II via IRA were similar to those of insulin. Furthermore, IGF‐II like insulin effectively stimulated cell cycle progression from the G0/G1 to the S and G2/M phases. Interestingly, AP‐1‐mediated gene expression, that was reported to be negatively regulated by Gsk3β was only weakly increased after IGF‐II stimulation. Our present data suggest that the coordinated activation or deactivation of Akt, Gsk3β, and Erk may account for IGF‐II mitogenic effects and support an active role for IRA in IGF‐II action. J. Cell. Biochem. 82: 610–618, 2001. © 2001 Wiley‐Liss, Inc.
Tumor necrosis factor‐α mediates RANK ligand stimulation of osteoclast differentiation by an autocrine mechanism†
Authors: Zou Wei , Hakim Imad , Tschoep Katharina , Endres Stefan , Bar‐Shavit Zvi 
Published: August 2002

AbstractOsteoblasts or bone marrow stromal cells are required as supporting cells for the in vitro differentiation of osteoclasts from their progenitor cells. Soluble receptor activator of nuclear factor‐κB ligand (RANKL) in the presence of macrophage colony‐stimulating factor (M‐CSF) is capable of replacing the supporting cells in promoting osteoclastogenesis. In the present study, using Balb/c‐derived cultures, osteoclast formation in both systems—osteoblast/bone‐marrow cell co‐cultures and in RANKL‐induced osteoclastogenesis—was inhibited by antibody to tumor necrosis factor‐α (TNF‐α), and was enhanced by the addition of this cytokine. TNF‐α itself promoted osteoclastogenesis in the presence of M‐CSF. However, even at high concentrations of TNF‐α the efficiency of this activity was much lower than the osteoclastogenic activity of RANKL. RANKL increased the level of TNF‐α mRNA and induced TNF‐α release from osteoclast progenitors. Furthermore, antibody to p55 TNF‐α receptors (TNF receptors‐1) (but not to p75 TNF‐α receptors (TNF receptors‐2) inhibited effectively RANKL‐ (and TNF‐α() induced osteoclastogenesis. Anti‐TNF receptors‐1 antibody failed to inhibit osteoclastogenesis in C57BL/6‐derived cultures. Taken together, our data support the hypothesis that in Balb/c, but not in C57BL/6 (strains known to differ in inflammatory responses and cytokine modulation), TNF‐α is an autocrine factor in osteoclasts, promoting their differentiation, and mediates, at least in part, RANKL's induction of osteoclastogenesis. © 2001 Wiley‐Liss, Inc.
Hypoxia‐induced increase in intracellular calcium concentration in endothelial cells: Role of the Na+‐glucose cotransporter
Authors: Berna Nancy , Arnould Thierry , Remacle José , Michiels Carine 
Published: August 2002

AbstractHypoxia is a common denominator of many vascular disorders, especially those associated with ischemia. To study the effect of oxygen depletion on endothelium, we developed an in vitro model of hypoxia on human umbilical vein endothelial cells (HUVEC). Hypoxia strongly activates HUVEC, which then synthesize large amounts of prostaglandins and platelet‐activating factor. The first step of this activation is a decrease in ATP content of the cells, followed by an increase in the cytosolic calcium concentration ([Ca2+]i) which then activates the phospholipase A2 (PLA2). The link between the decrease in ATP and the increase in [Ca2+]i was not known and is investigated in this work. We first showed that the presence of extracellular Na+ was necessary to observe the hypoxia‐induced increase in [Ca2+]i and the activation of PLA2. This increase was not due to the release of Ca2+ from intracellular stores, since thapsigargin did not inhibit this process. The Na+/Ca2+ exchanger was involved since dichlorobenzamil inhibited the [Ca2+]i and the PLA2 activation. The glycolysis was activated, but the intracellular pH (pHi) in hypoxic cells did not differ from control cells. Finally, the hypoxia‐induced increase in [Ca2+]i and PLA2 activation were inhibited by phlorizin, an inhibitor of the Na+‐glucose cotransport. The proposed biochemical mechanism occurring under hypoxia is the following: glycolysis is first activated due to a requirement for ATP, leading to an influx of Na+ through the activated Na+‐glucose cotransport followed by the activation of the Na+/Ca2+ exchanger, resulting in a net influx of Ca2+. J. Cell. Biochem. 84: 115–131, 2002. © 2001 Wiley‐Liss, Inc.
Hydrophobic similarity between molecules: A MST‐based hydrophobic similarity index
Authors: Muñoz J. , Barril X. , Hernández B. , Orozco Modesto , Luque F. Javier 
Published: August 2002

AbstractA similarity index based on the hydrophilic/hydrophobic properties of molecules is presented. Such an index is defined based on the fractional partition of the free energy of solvation developed within the framework of the self‐consistent reaction field MST model, which divides the free energy of solvation or the free energy of transfer into contributions assigned to the surface elements defining the solute/solvent interface. These surface contributions can be integrated to derive atomic or group contributions. The suitability of the index to compute the molecular similarity based on hydrophobic/hydrophilic properties is examined by considering their application in a variety of test systems, including structure‐activity relationships, absorption properties, and molecular recognition. The similarity index is expected to be a very powerful tool in molecular similarity studies for compounds of chemical, biochemical, and pharmaceutical interest. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 554–563, 2002; DOI 10.1002/jcc.10055
Multidimensional scaling of combinatorial libraries without explicit enumeration
Authors: Agrafiotis Dimitris K. , Lobanov Victor S. 
Published: August 2002

AbstractA novel approach for the multidimensional scaling of large combinatorial libraries is presented. The method employs a multilayer perceptron, which is trained to predict the coordinates of the products on the nonlinear map from pertinent features of their respective building blocks. This method limits the expensive enumeration and descriptor generation to only a small fraction of products and, in addition, relieves the enormous computational effort required for the low‐dimensional embedding by conventional iterative multidimensional scaling algorithms. In effect, the method provides an explicit mapping function from reagents to products, and allows the vast majority of compounds to be projected without constructing their connection tables. The advantages of this approach are demonstrated using two combinatorial libraries based on the reductive amination and Ugi reactions, and three descriptor sets that are commonly used in similarity searching, diversity profiling and structure–activity correlation. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1712–1722, 2001
Classification of 6‐(14,7,4) designs with nontrivial automorphism groups
Authors: Khosrovshahi G. B. , Mohammad‐Noori M. , Tayfeh‐Rezaie B. 
Published: August 2002

AbstractIn this paper, we introduce some intersection matrices for t‐designs. Utilizing these matrices together with a modified version of a backtracking algorithm, we classify all 6‐(14,7,4) and 5‐(13,6,4) designs with nontrivial automorphism groups and obtain 13 and 21 such designs, respectively. © 2002 Wiley Periodicals, Inc. J Combin Designs 10: 180–194, 2002; Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/jcd.10004
Specificity of autoantibodies to SS‐A/Ro on a transfected and overexpressed human 60 kDa Ro autoantigen substrate
Authors: Fritzler Marvin J. , Hanson Cheryl , Miller Joan , Eystathioy Theophany 
Published: August 2002

AbstractThe objective of this study was to analyze apparently discrepant results that arose during the use of an indirect immunofluorescence (IIF) assay using transfected HEp‐2 cells to detect anti‐SS‐A/Ro autoantibodies in human sera. Fourteen sera that had SS‐A/Ro antibodies as detected on this commercial substrate, but did not have antibodies to SS‐A/Ro as determined by double immunodiffusion (ID) or enzyme‐linked immunosorbent assay (ELISA), were studied by immunoprecipitation (IP) of radiolabeled cell extracts and full‐length recombinant SS‐A/Ro. A multi‐antigen strip immunoblotting (IB) assay containing both the 52‐ and 60‐kDa antigens was included in the analysis. We confirmed that 12 of 14 of the sera under study had antibodies to SS‐A/Ro protein antigens as determined by at least one other immunoassay. One serum had antibodies to hyRNA but no detectable reactivity with the 52‐ or 60‐kDa antigens. One serum remained negative in all assays for SS‐A/Ro autoantibodies. J. Clin. Lab. Anal. 16:103–108, 2002. © 2002 Wiley‐Liss, Inc.
Simultaneous determination of total plasma glutathione, homocysteine, cysteinylglycine, and methionine by high‐performance liquid chromatography with electrochemical detection
Authors: Houze Pascal , Gamra Stéphanie , Madelaine Isabelle , Bousquet Bernard , Gourmel Bernard 
Published: August 2002

AbstractWe here describe an ion‐exchange high‐performance liquid chromatography technique with electrochemical detection for rapid quantification of glutathione, homocysteine, cysteinylglycine, and methionine. The analytical validation of the technique showed within‐assay and between‐assay coefficients of variation between 3.1 and 4.3%, and 3.7 and 8.6%, respectively. Percentages of recovery for overload and dilution tests were between 87 and 120%. Detection limits were 1 μmol/L for methionine and 0.5 μmol/L for other compounds. There was no interference with any physiological and pharmacological substances possessing a thiol function. Aminothiol concentrations determined in 100 control subjects (50 women and 50 men) showed no age‐ or sex‐rated differences for except for homocysteine which was increased (+ 28%) in oldest subjects of both sexes. In 60 patients at risk (30 with chronic renal failure, 30 with diabetes), homocysteine concentration was significantly increased. No variation in other aminothiols was observed in diabetic subjects. Methionine was decreased and cysteinylglycine was increased in patients with chronic renal failure. The present technique—rapid, easy to use, and reliable—appears suitable for routine application in the exploration of aminothiol metabolic pathways including mechanisms of hyperhomocysteinemia. J. Clin. Lab. Anal. 15:144–153, 2001. © 2001 Wiley‐Liss, Inc.
Differential item functioning in a Spanish translation of the Beck Depression Inventory
Authors: Azocar Francisca , Areán Patricia , Miranda Jeanne , Muñoz Ricardo F. 
Published: August 2002

AbstractBrief and culturally compatible measures of depression are necessary, yet most depression scales are translated without regard for cultural biases. In this study, 292 medical outpatients completed an English or a Spanish‐translated and back‐translated version of the Beck Depression Inventory (BDI). The BDI items were analyzed for bias between Spanish and English‐speaking patients to determine the equivalence of the scale. A Differential Item Function (DIF) using a Mantel Haenszel Approach for Ordered Response Categories was used to analyze how likely subjects in the two ethnic groups were to endorse each response category. The results suggest that regardless of level of depression, Latinos are more likely to endorse items reflecting tearfulness and punishment, and less likely to endorse inability to work. Cultural interpretations and recommendations for use of the BDI are discussed. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 355–365, 2001.
Thought Field Therapy: Response to our critics and a scrutiny of some old ideas of social science
Authors: Callahan Roger J. 
Published: August 2002

AbstractThought Field Therapy (TFT) is criticized for not following the usual social science guidelines in research that is appropriate for minimum impact therapies. The usual research guidelines are due to a social science bias where crucial subjective reports are ignored, where tests of statistical significance and control groups are required. TFT may be closer to “hard science” than social science due to extraordinarily high level of success. A few valid points are acknowledged and were already covered, such as importance of autonomic balance when raising SDNN and necessity to restrict movement when electrocardiograph methods not used in measuring heart rate variability. Rejected as possible explanations of TFT's robust results are: placebo, regression to the mean (inappropriate in high and low heart rate variability), and passage of time when such time is merely minutes. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 1251–1260, 2001.
Depressive symptom patterns in patients with Parkinson's disease and other older adults
Authors: Erdal Kristi J. 
Published: August 2002

AbstractResearch on depression in Parkinson's disease (PD) has suggested that PD patients experience a qualitatively different depression from that of other older adults, endorsing fewer cognitive symptoms of depression (e.g., guilt, failure) and greater somatic (e.g., poor sleep) and mood symptoms (e.g., sadness, hopelessness); however, this has never been tested directly. In the present study, two PD groups, one with cognitive impairment (PD + CI; n = 26) and one without cognitive impairment (PD; n = 45), and three control groups of older adults were compared on measures of depressive symptomatology. The control groups included a physically disabled group (n = 46), a cognitively impaired group (CI; n = 21), and a healthy group (n = 50). Confirmatory factor analysis verified a four‐factor model of depressive symptoms (Cognitive, Mood, Somatic, and Fatigue symptoms). Comparisons revealed that the PD group had a depressive‐symptom pattern that was not significantly different from the disabled and healthy groups. The PD + CI group had a symptom pattern that was more similar to the CI group than to the PD group. Implications for the conceptualization of depression in older adults are discussed. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 1559–1569, 2001.
MMPI‐2 profiles of Gulf and Vietnam combat veterans with chronic posttraumatic stress disorder
Authors: Glenn D. Michael , Beckham Jean C. , Sampson William S. , Feldman Michelle E. , Hertzberg Michael A. , Moore Scott D. 
Published: August 2002

AbstractThe current study examined service era differences in a sample of 172 Gulf and Vietnam outpatient veterans with combat‐related posttraumatic stress disorder (PTSD). Participants completed the MMPI‐2 and several additional self‐report measures of symptom severity (PTSD, depression, anxiety, hostility, and health complaints). Results indicated that MMPI‐2 profiles differed significantly according to service era with Vietnam veterans scoring higher on scales 2, 8, and 0 and lower on scale 9 than did Gulf veterans. Examination of group means derived from parametric analysis of MMPI‐2 data suggested a mean two‐point code type of 2–8/8–2 for Vietnam veterans and 1–8/8–1 for Gulf veterans. In contrast, when the data were examined using descriptive techniques based on frequency counts of individual MMPI‐2 profiles, the most frequently occurring two‐point codetype was 7–8/8–7 for Vietnam veterans, and 6–8/8–6 for Gulf veterans. In addition, Gulf veterans reported a greater number of total health complaints than Vietnam veterans, whereas Vietnam veterans reported a greater number of physician‐diagnosed physical conditions. Potential advantages of incorporating descriptive approaches versus parametric methods when examining profile data are also presented. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 371–381, 2002.
Expression of the thrombin receptor (PAR‐1) during rat skeletal muscle differentiation
Authors: Chevessier Frédéric , Hantaï Daniel , Verdière‐Sahuqué Martine 
Published: August 2002

AbstractThe serine protease thrombin has been proposed to be involved in neuromuscular plasticity. Its specific receptor “protease activated receptor‐1” (PAR‐1), a G protein‐coupled receptor, has been shown to be expressed in myoblasts but not after fusion (Suidan et al., 1996 J Biol Chem 271:29162–29169). In the present work we have investigated the expression of PAR‐1 during rat skeletal muscle differentiation both in vitro and in vivo. Primary cultures of rat foetal skeletal muscle, characterized by their spontaneous contractile activity, were used for exploration of PAR‐1 by RT‐PCR, immunocytochemistry and Western blotting. Our results show that PAR‐1 mRNA and protein are both present in myoblasts and myotubes. Incubation of myotubes loaded with fluo‐3‐AM in presence of thrombin (200 nM) or PAR‐1 agonist peptide (SFLLRN, 500 μM), induced the intracellular release of calcium indicating the activation of PAR‐1. Blockade of contractile activity by tetrodotoxin (TTX, 6 nM) did not modify either PAR‐1 synthesis or its cellular localization. Investigation of PAR‐1 on rat muscle cryostat sections at Day 18 of embryogenesis and postnatal Days 1, 5, and 10 indicated that this protein is first expressed in the cytoplasm and that it later localizes to the membrane. Moreover, its expression correlates with myosin heavy chain transitions occurring during post‐natal period and is restricted to primary fibers. Taken together, these results suggest that PAR‐1 expression is not related to contractile activity but to myogenic differentiation. © 2001 Wiley‐Liss, Inc.
Effect of age and hypoxia on TGFβ1 receptor expression and signal transduction in human dermal fibroblasts: Impact on cell migration
Authors: Mogford Jon E. , Tawil Nabil , Chen Alexandria , Gies David , Xia Yuping , Mustoe Thomas A. 
Published: August 2002

AbstractWound healing is critically affected by age, ischemia, and growth factors such as TGFβ1. The combined effect of these factors on fibroblast migration, an essential component of wound healing, is poorly understood. To address this deficiency, we examined expression of TGFβ receptor type I and II (TGFβRI and RII) under normoxia or hypoxia (1% O2) in cultured human dermal fibroblasts (HDFs) from young (ages 24–33) and aged (ages 61–73) adults. TGFβRI and RII expression was similar in both groups under normoxia. Hypoxia did not alter receptor levels in young HDFs but significantly decreased TGFβRI in aged cells (12 and 43%, respectively). Additionally, young cells displayed a 50% increase in activation of p42/p44 mitogen‐activated kinase by TGFβ1 (2–200 pg/ml) under hypoxia while aged cell levels of active p42/p44 decreased up to 24%. To determine functional outcomes of these findings, we measured the migratory capacity of the cells on type I collagen using a gold salt migration assay. Hypoxia increased the migratory index (MI) of young HDFs over normoxia by 30% but had no effect on aged cells. Under normoxia, TGFβ1 (1–1000 pg/ml) increased young HDF migration in a concentration‐dependent manner up to 109% over controls but minimally increased aged HDF migration (37%). Under hypoxia, TGFβ1 significantly increased young cell MI at all concentrations but was without effect on the aged HDF response. These data demonstrate that aged fibroblasts have an impaired migratory capacity with complete loss of responsiveness to hypoxia and deficits in the migratory and signal transduction responsiveness to TGFβ1 that may partly explain diminished healing capabilities often observed in aged patients. J. Cell. Physiol. 190: 259–265, 2002. © 2002 Wiley‐Liss, Inc.
Cultivation of rat marrow‐derived mesenchymal stem cells in reduced oxygen tension: Effects on in vitro and in vivo osteochondrogenesis
Authors: Lennon Donald P. , Edmison John M. , Caplan Arnold I. 
Published: August 2002

AbstractRat mesenchymal stem cells (rMSCs) represent a small portion of the cells in the stromal compartment of bone marrow and have the potential to differentiate into bone, cartilage, fat, and fibrous tissue. These mesenchymal progenitor cells were maintained as primary isolates and as subcultured cells in separate closed modular incubator chambers purged with either 95% air and 5% CO2 (20% or control oxygen) or 5% oxygen, 5% CO2, and 90% nitrogen (5% or low oxygen). At first passage, some cells from each oxygen condition were loaded into porous ceramic vehicles and implanted into syngeneic host animals in an in vivo assay for osteochondrogenesis. The remaining cells were continued in vitro in the same oxygen tension as for primary culture or were switched to the alternate condition. The first passage cells were examined for in vitro osteogenesis with assays involving the quantification of alkaline phosphatase activity and calcium and DNA content as well as by von Kossa staining to detect mineralization. Cultures maintained in low oxygen had a greater number of colonies as primary isolates and proliferated more rapidly throughout their time in vitro, as indicated by hemacytometer counts at the end of primary culture and increased DNA values for first passage cells. Moreover, rMSCs cultivated in 5% oxygen produced more bone than cells cultured in 20% oxygen when harvested and loaded into porous ceramic cubes and implanted into syngeneic host animals. Finally, markers for osteogenesis, including alkaline phosphatase activity, calcium content, and von Kossa staining, were elevated in cultures which had been in low oxygen throughout their cultivation time. Expression of these markers was usually increased above basal levels when cells were switched from control to low oxygen at first passage and decreased for cells switched from low to control oxygen. We conclude that rMSCs in culture function optimally in an atmosphere of reduced oxygen that more closely approximates documented in vivo oxygen tension. © 2001 Wiley‐Liss, Inc.