bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subchronic toxicity of chloral hydrate on rats: a drinking water study
Authors: Poon R. , Nakai J. , Yagminas A. , Benoit F. , Moir D. , Chu I. , Valli V. E. 
Published: October 2002

AbstractThe subchronic toxicity of chloral hydrate, a disinfection byproduct, was studied in rats following 13 weeks of drinking water exposure. Male (262 ± 10 g) and female (190 ± 8 g) Sprague‐Dawley rats, ten animals per group, were administered chloral hydrate via drinking water at 0.2, 2, 20 and 200 ppm. Control animals received distilled water only. Gross and microscopic examinations, serum chemistry, hematology, biochemical analysis, neurogenic amine analysis and serum trichloroacetic acid (TCA) analysis were performed at the end of the treatment period. Bronchoalveolar fluids were collected at necropsy and urine specimens were collected at weeks 2, 6 and 12 for biochemical analysis. No treatment‐related changes in food and water intakes or body weight gains were observed. There were no significant changes in the weights of major organs. Except for a mild degree of vacuolation within the myelin sheath of the optic nerves in the highest dose males, there were no notable histological changes in the tissues examined. Statistically significant treatment‐related effects were biochemical in nature, with the most pronounced being increased liver catalase activity in male rats starting at 2 ppm. Liver aldehyde dehydrogenase (ALDH) was significantly depressed, whereas liver aniline hydroxylase activity was significantly elevated in both males and females receiving the highest dose. A dose‐related increase in serum TCA was detected in both males and females starting at 2 ppm. An in vitro study of liver ALDH confirmed that chloral hydrate was a potent inhibitor, with an IC50 of 8 µM, whereas TCA was weakly inhibitory and trichloroethanol was without effect. Analysis of brain biogenic amines was conducted on a limited number (n = 5) of male rats in the control and high dose groups, and no significant treatment‐related changes were detected. Taking into account the effect on the myelin sheath of male rats and the effects on liver ALDH and aniline hydroxylase of both males and females at the highest dose level, the no‐observed‐effect level (NOEL) was determined to be 20 ppm or 1.89 mg kg−1 day−1 in males and 2.53 mg kg−1 day−1 in females. This NOEL is ca. 1000‐fold higher than the highest concentration of chloral hydrate reported in the municipal water supply. Copyright © 2002 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
Targeted disruption of hsf1 leads to lack of thermotolerance and defines tissue‐specific regulation for stress‐inducible Hsp molecular chaperones
Authors: Zhang Yan , Huang Lei , Zhang Jing , Moskophidis Demetrius , Mivechi Nahid F. 
Published: October 2002

AbstractThe rapid synthesis of heat shock proteins (Hsps) in cells subjected to environmental challenge is controlled by heat shock transcription factor‐1 (Hsf1). Regulation of Hsps by Hsf1 is highly complex and, in the whole organism, remains largely unexplored. In this study, we have used mouse embryo fibroblasts and bone marrow progenitor cells from hsf1−/− mice as well as hsp70.3‐lacZ knock‐in mice bred on the hsf1deficient genetic background (hsf1−/−‐hsp70.3+/−‐lacZ), to further elucidate the function of Hsf1 and its participation as a transcriptional activator of Hsp70 synthesis under normal or heat‐induced stress conditions in vitro and in vivo. The results revealed that heat‐induced Hsp70 expression in mouse tissue is entirely controlled by Hsf1, whereas its activity is not required for tissue‐specific constitutive Hsp70 expression. We further demonstrate that Hsf1 is critical for maintaining cellular integrity after heat stress and that cells from hsf1−/− mice lack the ability to develop thermotolerance. This deficiency is explained by the elimination of stress‐inducible Hsp70 and Hsp25 response in the absence of Hsf1 activity, leading to a lack of Hsp‐mediated inhibition of apoptotic cell death via both caspase‐dependent and caspase‐independent pathways. The pivotal role of the Hsf1 transactivator in regulating rapid synthesis of Hsps as a critical cellular defense mechanism against environmental stress‐induced damage is underlined. J. Cell. Biochem. 86: 376–393, 2002. © 2002 Wiley‐Liss, Inc.
Constitutive activation of met kinase in non‐small‐cell lung carcinomas correlates with anchorage‐independent cell survival
Authors: Qiao Hui , Hung Wesley , Tremblay Eric , Wojcik Joanna , Gui Jin , Ho Janet , Klassen Jennifer , Campling Barbara , Elliott Bruce 
Published: October 2002

AbstractLung cancer is currently the most frequent cause of cancer death in North America. Hepatocyte growth factor (HGF) and its receptor Met are frequently over‐expressed in non‐small‐cell lung carcinomas (NSCLC), but their potential role in tumor progression is not clearly known. To assess the role of HGF/Met signaling in lung carcinomas, we have examined the expression, activation status, and function of Met in NSCLC cell lines (n = 7), established from primary tumors or pleural fluids of cancer patients. We observed Met expression in three NSCLC cell lines, two of which exhibited constitutive tyrosine‐phosphorylation of Met, and Met kinase activity. In addition, the observed constitutive activation of Met was sustained under anchorage‐independent conditions, and correlated with phosphatidyl inositol 3‐kinase‐dependent cell survival. Immunoreactive HGF‐like protein was secreted by two Met‐positive and two Met‐negative NSCLC cell lines. However HGF activity, as determined by the ability to induce cell scattering and tyrosine‐phosphorylation of Met in reporter cell lines, was detected in conditioned medium from only one Met‐negative NSCLC cell line: none of the conditioned media from Met‐expressing NSCLC cell lines showed detectable HGF activity. Thus, constitutive activation of Met in NSCLC cell lines may occur at least in part through intracrine, or HGF‐independent mechanisms. Interestingly, additional paracrine stimulation with exogenous recombinant HGF was required for DNA synthesis and correlated with increased activation of ERK1/2 in all Met‐positive NSCLC cell lines, regardless of the basal activation status of Met. These findings indicate that a medium level of constitutive activation of Met occurs in some NSCLC cell lines, and correlates with survival of detached carcinoma cells; whereas additional paracrine stimulation by recombinant HGF is required for DNA synthesis. Thus constitutive and paracrine activation of Met may provide complementary signals that promote survival and proliferation, respectively, during tumor progression of NSCLC. J. Cell. Biochem. 86: 665–677, 2002. © 2002 Wiley‐Liss, Inc.
Expression of a releasable form of annexin II by human keratinocytes
Authors: Karimi‐Busheri Feridoun , Marcoux Yvonne , Tredget Edward E. , Li Liang , Zheng Jing , Ghoreishi Mina , Weinfeld Michael , Ghahary Aziz 
Published: October 2002

AbstractAnnexin II is a multifunctional calcium‐dependent phospholipid binding protein whose presence in epidermis has previously been reported. However, like other members of annexin family, annexin II has been regarded as either an intracellular protein or associated with the cellular membrane. Here, we report the presence of a releasable annexin II and p11, two monomers of annexin II tetramer, in keratinocyte‐conditioned medium (KCM). Proteins present in KCM were fractionated on a gel filtration column and following further evaluation, a releasable protein with apparent MW of 36 kDa was identified. Further characterization identified this protein as the p36 monomer of annexin II tetramer. The phospho‐tyrosine antibody did not visualize this protein as the phosphorylated form of p36. Several experiments were conducted to examine whether this protein is soluble or associated with keratinocyte cell membranes in the conditioned medium. A centrifugation of conditioned medium was not able to bring this protein down into the pellet. Surprisingly, the results of Western analysis identified p36 and p11, two monomers of the annexin II tetramer, in conditioned medium derived from either keratinocytes cultured alone or keratinocytes co‐cultured with fibroblasts. In contrast to the keratinocyte‐conditioned medium in which annexin II was easily detectable, both monomers were barely detectable in conditioned medium collected from dermal fibroblasts. This finding was in contrast to the cell lysates in which p36 was detectable in both keratinocytes and fibroblasts. However, the amount of this protein was markedly higher in keratinocyte lysate relative to that of dermal fibroblasts. Conditioned medium derived from keratinocyte established from adult showed a higher level of annexin II compared to that of keratinocytes established from newborn babies. The expression of p11 seems to increase with differentiation of keratinocytes derived from either adult or newborn skin samples. When the site of annexin synthesis in human skin was examined by immunohistochemical staining, the antibody for p36 localized the annexin to the keratinocyte cell members in the basal and suprabasal keratinocytes. In conclusion, Western blot detection of both p36 and p11 in conditioned medium from skin cells revealed that human keratinocytes, but not fibroblasts, express a releasable monomer form of annexin II which is regulated by differentiation status of keratinocytes. This finding is consistent with the localization of annexin II detected by immunohistochemical staining. J. Cell. Biochem. 86: 737–747, 2002. © 2002 Wiley‐Liss, Inc.
Involvement of PI3‐kinase and its association with c‐Src in PTH‐stimulated rat enterocytes
Authors: Gentili Claudia , Morelli Susana , Russo de Boland Ana 
Published: October 2002

AbstractPhosphoinositide‐3‐kinase (PI3K) is a lipid kinase, which phosphorylates the D3 position of phosphoinositides, and is known to be activated by a host of protein tyrosine kinases. PI3K plays an important role in mitogenesis in several cell systems. However, whether parathyroid hormone (PTH) affects the activity and functional roles of PI3K in intestinal cells remain to be determined. The objective of this study was to identify and characterize the PI3K pathway, and its relation to other non‐receptor tyrosine kinases in mediating PTH signal transduction in rat enterocytes. PTH dose‐ and time‐dependently increased PI3K activity with a peak occurring at 2 min. The tyrosine kinase inhibitor genistein, c‐Src inhibitor PP1 and two structurally different inhibitors of PI3K, LY294002 and wortmannin, suppressed PI3K activity dependent on PTH. Co‐immunoprecipitation analysis showed a constitutive association between c‐Src and PI3K, which was enhanced by PTH treatment, suggesting that the cytosolic tyrosine kinase forms an immunocomplex with PI3K probably via the N‐SH2 domain of the p85α regulatory subunit. In response to PTH, tyrosine phosphorylation of p85α was enhanced, effect that was abolished by PP1, the inhibitor of c‐Src kinase. PTH causes a rapid (0.5–5 min) phosphorylation of Akt/PKB, effect that was abrogated by PI3K inhibitors, indicating that in rat enterocytes, PI3K is an upstream mediator of Akt/PKB activation by PTH. We report here that PI3K is also required for PTH activation of the mitogen‐activated protein kinases ERK1 and ERK2. Taken together, the present study demonstrate, for the first time, that PTH rapidly and transiently stimulates PI3K activity and its down effector Akt/PKB in rat enterocytes playing c‐Src kinase a central role in PTH‐dependent PI3K activation and that PI3K signaling pathway contributes to PTH‐mediated MAPK activation. J. Cell. Biochem. 86: 773–783, 2002. © 2002 Wiley‐Liss, Inc.
Runx1, c‐Myb, and C/EBPα couple differentiation to proliferation or growth arrest during hematopoiesis
Authors: Friedman Alan D. 
Published: October 2002

AbstractImmature hematopoietic precursors proliferate as they differentiate, whereas terminal differentiation is associated with cell cycle arrest. Stem cell lineage commitment and subseqent maturation is regulated predominantly by transcription factors. Runx1 and c‐Myb act in early stage hematopoietic cells to both stimulate proliferation and differentiation, whereas C/EBPα, and perhaps other C/EBP family members, block progression from G1 to S and induce terminal maturation. Coupling of differentiation to either proliferation or growth arrest by transcription factors is likely an important regulatory mechanism in multiple developmental systems. J. Cell. Biochem. 86: 624–629, 2002. © 2002 Wiley‐Liss, Inc.
Support vector machines for predicting HIV protease cleavage sites in protein
Authors: Cai Yu‐Dong , Liu Xiao‐Jun , Xu Xue‐Biao , Chou Kuo‐Chen 
Published: October 2002

AbstractKnowledge of the polyprotein cleavage sites by HIV protease will refine our understanding of its specificity, and the information thus acquired is useful for designing specific and efficient HIV protease inhibitors. The pace in searching for the proper inhibitors of HIV protease will be greatly expedited if one can find an accurate, robust, and rapid method for predicting the cleavage sites in proteins by HIV protease. In this article, a Support Vector Machine is applied to predict the cleavability of oligopeptides by proteases with multiple and extended specificity subsites. We selected HIV‐1 protease as the subject of the study. Two hundred ninety‐nine oligopeptides were chosen for the training set, while the other 63 oligopeptides were taken as a test set. Because of its high rate of self‐consistency (299/299=100%), a good result in the jackknife test (286/299=95%) and correct prediction rate (55/63 = 87%), it is expected that the Support Vector Machine method can be referred to as a useful assistant technique for finding effective inhibitors of HIV protease, which is one of the targets in designing potential drugs against AIDS. The principle of the Support Vector Machine method can also be applied to analyzing the specificity of other multisubsite enzymes. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 267–274, 2002
Ab initioand DFT studies on van der Waals trimers: The OCS · (CO2)2complexes
Authors: Valdés H. , Sordo J. A. 
Published: October 2002

AbstractAb initiocalculations [MP2, MP4SDTQ, and QCISD(T)] using different basis sets [6‐31G(d,p), cc‐pVXZ (X = D, T, Q), and aug‐cc‐pVDZ] and density functional theory [B3LYP/6‐31G(d,p)] calculations were carried out to study the OCS · (CO2)2van der Waals trimer. The DFT has proved inappropriate to the study of this type of systems where the dispersion forces are expected to play a relevant role. Three minima isomers (two noncyclic and one cyclic) were located and characterized. The most stable isomer exhibits a noncyclic barrel‐like structure whose bond lengths, angles, rotational constants, and dipole moment agree quite well with the corresponding experimental values of the only structure observed in recent microwave spectroscopic studies. The energetic proximity of the three isomers, with stabilization energies of 1442, 1371, and 1307 cm−1, respectively, at the CBS‐MP2/cc‐pVXZ (X = D, T, Q) level, strongly suggests that the two unobserved structures should also be detected as in the case of the (CO2)3trimer where both noncyclic and cyclic isomers have been reported to exist. The many‐body symmetry‐adapted perturbation theory is employed to analyze the nature of the interactions leading to the formation of the different structures. The three‐body contributions are small and stabilizing for the two most stable structures and almost negligible for the cyclic isomer. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 444–455, 2002; DOI 10.1002/jcc.10041
Effective atom volumes for implicit solvent models: comparison between Voronoi volumes and minimum fluctuation volumes
Authors: Schaefer Michael , Bartels Christian , Leclerc Fabrice , Karplus Martin 
Published: October 2002

AbstractAn essential element of implicit solvent models, such as the generalized Born method, is a knowledge of the volume associated with the individual atoms of the solute. Two approaches for determining atomic volumes for the generalized Born model are described; one is based on Voronoi polyhedra and the other, on minimizing the fluctuations in the overall volume of the solute. Volumes to be used with various parameter sets for protein and nucleic acids in the CHARMM force field are determined from a large set of known structures. The volumes resulting from the two different approaches are compared with respect to various parameters, including the size and solvent accessibility of the structures from which they are determined. The question of whether to include hydrogens in the atomic representation of the solute volume is examined. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1857–1879, 2001
Balanced arrays of strength two from block designs
Authors: Sinha Kishore , Dhar Vanshi , Saha G. M. , Kageyama Sanpei 
Published: October 2002

AbstractSome constructions of balanced arrays of strength two are provided by use of rectangular designs, group divisible designs, and nested balanced incomplete block designs. Some series of such arrays are also presented as well as orthogonal arrays, with illustrations. © 2002 Wiley Periodicals, Inc. J Combin Designs 10: 303–312, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10016
Comparison of seven‐subtest and Satz‐Mogel short forms of the WAIS‐III
Authors: Kulas Joseph F. , Axelrod Bradley N. 
Published: October 2002

AbstractIntellectual functioning remains an important domain of functioning to be measured. To reduce the lengthy administration time, numerous short forms of the WAIS‐III have been devised. The present study aimed to compare two methods of applying short forms of the WAIS‐3 within a clinical population. The results revealed that both item‐reduced and selected subtest short forms provide excellent predictions of full administration WAIS‐3 summary and index scores. The Satz‐Mogel short form appeared to provide higher predictive power than the seven‐subtest short forms and accounted for a higher number of cases within 6 points of the obtained scores from the full administration. However, the Satz‐Mogel short form was inferior to the seven‐subtest short forms in terms of the reliability of the index and summary IQ scores. As found in previous research, a trade‐off occurs between the predictive power and the reliability of a short form. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 773‐782, 2002.
Prenatal sonographic diagnosis of dilated cavum vergae
Authors: Sahinoglu Zeki , Uludogan Mehmet , Delikara Mehmet N. 
Published: October 2002

AbstractSeveral cases of enlarged cavum vergae have been reported, but prenatal diagnosis of this condition is very rare. We report 3 cases of dilated cavum vergae diagnosed prenatally using sonography. In 1 of the 3 fetuses, ventriculomegaly and lumbar meningomyelocele were additional sonographic findings. In 1 of the 3 infants, a stereotactic cyst–peritoneal shunt was placed at 6 months of age to relieve intracranial hypertension due to progressive enlargement of the cavum vergae. The infant who had a meningomyelocele required surgical repair of this defect shortly after birth; in the third infant, the dilated cavum vergae remained asymptomatic, and no surgery was necessary. When interhemispheric cystic lesions are identified prenatally, physicians must distinguish them from pathologic cysts and determine whether associated malformations are present. Sonography is useful for both the differential diagnosis and identification of associated anomalies. © 2002 Wiley Periodicals, Inc. J Clin Ultrasound 30:378–383, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jcu.10083
Phagocytosis of apoptotic cells by liver: A morphological study
Authors: Dini Luciana , Pagliara Patrizia , Carlà Emanuela C. 
Published: October 2002

AbstractThe present review deals with the morphological features of the removal of apoptotic cells by liver. The engulfment of cells undergoing apoptosis can be considered a specialized form of phagocytosis, playing a major role in the general tissue homeostasis in physiological and pathological conditions. In fact, defects of phagocytosis of apoptotic cells might have deleterious consequences for neighboring healthy cells, i.e., pathogenesis of inflammatory disease or dysregulation of the immune system. Phagocytosis of apoptotic cells by liver is a complex phenomenon, involving multiple molecular mechanisms of recognition (i.e., lectin‐like receptors and receptors for externalized phosphatydilserine) of both parenchymal (hepatocytes) and nonparenchymal (Kupffer and endothelial cells) liver cells, often operating in cooperation. The data discussed in the present review are drawn from studies of phagocytosis of apoptotic cells in the liver, carried out with in vivo and in situ adhesion experiments as well as in vitro assays. Our results indicate that the three main liver cell types (hepatocytes, Kupffer, and endothelial cells) are able to recognize and internalize apoptotic cells by means of specific receptors (galactose and mannose‐specific receptor; receptor for phosphatydilserine) and by cytoskeletal reorganization that favors the engulfment of the apoptotic cells. The “flags” for the identification of apoptotic cells by the liver are modifications of the surface of dead cells, i.e., sugar residues and phosphatydilserine exposition. Vitronectin receptor is not involved in such a recognition. The adhesions between modified cell surfaces of apoptotic cells and phagocytes generate cytoplasmatic signaling pathways that drive apoptotic cells to their final fate within the phagocytes (i.e., lysosomal digestion). Microsc. Res. Tech. 57:530–540, 2002. © 2002 Wiley‐Liss, Inc.
Calcitonin gene‐related peptide (CGRP)‐containing nerve fibers in bone tissue and their involvement in bone remodeling
Authors: Irie Kazuharu , Hara‐Irie Fumiko , Ozawa Hidehiro , Yajima Toshihiko 
Published: October 2002

AbstractBone remodeling is a process of bone renewal accomplished by osteoclastic bone resorption and osteoblastic bone formation. These two activities are regulated by systemic hormones and by local cytokines and growth factors. Moreover, the nervous system and certain neuropeptides seem to be involved in regulation of bone remodeling. In this paper, we focus on the distribution of CGRP‐containing nerve fibers and their dynamics, and discuss the role of these fibers as a possible mechanism for nervous system involvement in regulation of bone remodeling. CGRP‐immunoreactive nerve fibers are widely distributed in bone tissue, such as periosteum and bone marrow, and show apparent regional distribution with different densities. They are often associated with blood vessels and show a beaded appearance. The wide distribution of CGRP‐immunoreactive nerve fibers in bone tissue and the changes in distribution during bone development and regeneration suggest the involvement of these fibers in bone remodeling. The effect of CGRP on bone remodeling could partly be through its action on blood vessels, thereby regulating local blood flow. Moreover, in vitro biochemical data and the localization of CGRP‐immunoreactive nerve fibers in the vicinity of bone cells suggest that they are directly involved in local regulation of bone remodeling by elevating the concentration of CGRP in the microenvironment around bone cells, especially during bone growth or repair. Microsc. Res. Tech. 58:85–90, 2002. © 2002 Wiley‐Liss, Inc.