bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term treatment of myasthenia gravis with immunoadsorption
Authors: Haas Martin , Mayr Norbert , Zeitlhofer Josef , Goldammer Andreas , Derfler Kurt 
Published: October 2002

AbstractAcute treatment of myasthenic crisis with immunoadsorption (IA) or plasma exchange is well established. The efficiency of chronic apheresis therapy in myasthenia gravis (MG), however, and its efficacy in reducing concomitant potentially harmful immunosuppressive therapy, is unknown. We treated 13 patients with therapy‐resistant MG or severe steroid or azathioprine therapy‐related side effects, or both, with long‐term IA [median, 38 (range: 16–59) months]. IA was performed every second day until partial remission was achieved (modified Osserman score <2). Subsequently, oral immunosuppressive therapy was reduced and the frequency of IA adapted to the clinical symptoms. After initiation of IA the mean (SEM) Osserman score decreased from 3.23 ± 0.12 to 1.23 ± 0.08 within 1 month (P < 0.01). Mean azathioprine dose was reduced concomitantly from 89 ± 9.4 mg/day to 56 ± 11 mg/day (P < 0.05), and mean prednisolone dose from 41 ± 7.6 mg/day to 22 ± 8.5 mg/day (P < 0.05). After 36 months the number of IA‐sessions/month had been reduced from 4.81 ± 0.24 to 2.64 ± 0.4 (P < 0.05), the mean azathioprine dose to 25 ± 17 mg/day and the mean prednisolone dose to 9 ± 3.6 mg/day. Six out of thirteen patients were weaned from IA after a median of 33 (range, 16–50) months and a decrease of the Osserman score to 0.33 ± 0.33. In these patients MG remained stable during a follow‐up period of 28 (range, 16–38) months. We conclude that long‐term IA enables the reduction of oral immunosuppressants in patients with contraindications or resistance to steroid and azathioprine therapy. Furthermore, almost 50% of the patients can be weaned from IA with then substantial lower need of further immunosuppressive therapy. J. Clin. Apheresis 17:84–87, 2002. © 2002 Wiley‐Liss, Inc.
1,25(OH)2‐vitamin D3 induces translocation of the vitamin D receptor (VDR) to the plasma membrane in skeletal muscle cells
Authors: Capiati Daniela , Benassati Silvia , Boland Ricardo L. 
Published: October 2002

Abstract1,25‐dihydroxy‐vitamin D3 (1,25(OH)2D3), the hormonally active form of vitamin D3, acts through two different mechanisms. In addition to regulating gene expression via the specific intracellular vitamin D receptor (VDR), 1,25(OH)2D3 induces rapid, non‐transcriptional responses involving stimulation of transmembrane signal transduction pathways. The activation of second messengers supports the hypothesis that a membrane‐bound steroid receptor similar to those that mediate peptide hormone biology exists. Skeletal muscle is a target tissue for 1,25(OH)2D3. Avian embryonic skeletal muscle cells (myoblasts/myotubes) have been shown to respond both genomically and non‐genomically to the hormone. The present study provides evidence indicating that short‐term treatment (1–10 min) with 1,25(OH)2D3 induces translocation of the VDR from the nuclear to the microsomal fraction in chick myoblasts. This translocation is blocked by colchicine, genistein, or herbimycin, suggesting the involvement of microtubular transport and tyrosine kinase/s in the relocation of the receptor. By isolation of plasma membranes, it was demonstrated that the hormone increases the amounts of VDR specifically in this fraction. These results suggest that the nuclear VDR may be the receptor that mediates the non‐genomic effects of 1,25(OH)2D3 in chick myoblasts. J. Cell. Biochem. 86: 128–135, 2002. © 2002 Wiley‐Liss, Inc.
Retinoid X receptors and retinoid response in neuroblastoma cells
Authors: Rana Birju , Veal Gareth J. , Pearson Andrew D.J. , Redfern Christopher P.F. 
Published: October 2002

AbstractRetinoic acid (RA) modulates differentiation and apoptosis of neural cells via RA receptors (RARs) and retinoid X receptors (RXRs). Neuroblastoma cells are potentially useful models for elucidating the molecular mechanisms of RA in neural cells, and responses to different isomers of RA have been interpreted in terms of differential homo‐ and heterodimerization of RXRs. The aim of this study was to identify the RXR types expressed in neuroblast and substrate‐adherent neuroblastoma cells, and to study the participation of these RXRs in RAR heterodimers. RXRβ was the predominant RXR type in N‐type SH SY 5Y cells and S‐type SH EP cells. Gel shift and supershift assays demonstrated that RARβ and RARγ predominantly heterodimerize with RXRβ. In SH SY 5Y cells, RARγ/RXRβ was the predominant heterodimer binding to the DR5 RARE in the absence of 9‐cisRA (9C), whereas the balance shifted in favor of RARβ/RXRβ in the presence of ligand. There was a marked difference between the N‐ and S‐type neuroblastoma cells in retinoid receptor–DNA interactions, and this may underlie the differential effects of retinoids in these neuroblastoma cell types. There was no evidence to indicate that 9C functions via RXR homodimers in either SH SY 5Y or SH EP neuroblastoma cells. The results of this study suggest that interactions between retinoid receptors and other nuclear proteins may be critical determinants of retinoid responses in neural cells. © 2002 Wiley‐Liss, Inc.
Metallothionein is required for zinc‐induced expression of the macrophage colony stimulating factor gene
Authors: Kanekiyo Masako , Itoh Norio , Kawasaki Atsuko , Matsuda Kimihiro , Nakanishi Tsuyoshi , Tanaka Keiichi 
Published: October 2002

AbstractMacrophage colony stimulating factor (M‐CSF) plays an important role in the proliferation and differentiation of mononuclear phagocytes. The present study investigates the effect of zinc on M‐CSF expression in MC3T3‐E1 and L929 cells. Zinc dose‐dependently increased M‐CSF mRNA levels. The time‐course of zinc‐induced M‐CSF mRNA expression peaked at 6 h. Stability studies of mRNA using actinomycin D revealed that zinc does not affect M‐CSF mRNA stability. We examined the function of the M‐CSF gene promoter using a luciferase reporter assay. A construct containing the −467/+39 region of the promoter was upregulated by zinc. In the presence of cycloheximide, zinc did not induce a greater increase in the M‐CSF mRNA than cycloheximide alone. To confirm the effect of MT on M‐CSF mRNA expression, mouse lung fibroblasts (MLFs) were prepared from MT+/+ and MT−/− mice. Zinc induced an increase in the expression of M‐CSF in MT+/+ MLFs, but this response was not evident in MT−/− MLFs. Moreover, overexpression of MT upregulated M‐CSF mRNA expression as well as M‐CSF secretion. Our findings suggest that MT expression mediates zinc regulation of M‐CSF gene expression at the transcriptional level. J. Cell. Biochem. 86: 145–153, 2002. © 2002 Wiley‐Liss, Inc.
Role of GST P1‐1 in mediating the effect of etoposide on human neuroblastoma cell line Sh‐Sy5y
Authors: Bernardini S. , Bellincampi L. , Ballerini S. , Ranalli M. , Pastore A. , Cortese C. , Federici G. 
Published: October 2002

AbstractThe oxidative stress could have a dual action on glutathione S‐transferase (GST) P1‐1 metabolism: transcriptional induction and/or polymerization. The former should represent a form of adaptation to oxidative stress and contribute to protect the cell, the latter one should activate apoptosis via c‐Jun N‐terminal kinase (JNK). We studied the effect of etoposide on human neuroblastoma cell line SH‐SY5Y and on an etoposide‐resistant clone to investigate whether a pleiotropic effect of etoposide on the redox status of the cell exists which is able to interfere with apoptosis through the GST P1‐1 system. Etoposide treatment was able to induce GST P1‐1 polymerization and activation of apoptosis. The data obtained from our etoposide‐resistant clone and the possibility to reverse the sensitive phenotype to a resistant one by means of hexyl‐glutathione preincubation, seem to suggest that cellular levels of glutathione have a key role in protecting GST P1‐1 by oxidation and consequently the cell's decision between life and death. J. Cell. Biochem. 86: 340–347, 2002. © 2002 Wiley‐Liss, Inc.
Differentiation‐dependent induction of CYP1A1 in cultured rat small intestinal epithelial cells, colonocytes, and human colon carcinoma cells: Basement membrane‐mediated apoptosis
Authors: Sterling Kenneth M. , Cutroneo Kenneth R. 
Published: October 2002

AbstractRat small intestinal epithelial cells and human colon adenocarcinoma cells cultured on Matrigel™ expressed the differentiation specific enzyme, sucrase‐isomaltase, as determined by indirect immunofluorescence. Rat small intestinal epithelial cells, rat colonocytes, and human colon adenocarcinoma cells developed an altered morphology when cultured on Matrigel and became apoptotic within 24–48 h. Benzo[a]pyrene and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin caused a 2‐ and 5‐fold induction, respectively, of ethoxyresorufin‐o‐deethylase activity in rat small intestinal epithelial cells cultured on Matrigel. Benzo[a]pyrene‐ or 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin‐induced ethoxyresorufin‐o‐deethylase activity in rat small intestinal epithelial cells cultured on plastic was not detected. 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin treatment caused a 14‐fold induction of transfected, rat CYP1A1‐promoter‐luciferase activity in rat small intestinal epithelial cells cultured on Matrigel. Benzo[a]pyrene and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin treatment induced ethoxyresorufin‐o‐deethylase activity by 6‐ and 1.6‐fold, respectively in rat colonocytes cultured on Matrigel. Induction of ethoxyresorufin‐o‐deethylase activity was not observed in rat colonocytes cultured on plastic. CYP1A1‐promoter‐luciferase activity was induced 3‐fold by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin in rat colonocytes cultured on Matrigel. Induction of CYP1A1‐promoter‐luciferase activity in rat small intestinal epithelial cells or rat colonocytes cultured on plastic was not observed. Ethoxyresorufin‐o‐deethylase activity in human colon adenocarcinoma cells, cultured on either plastic or Matrigel, was induced 7‐fold by benzo[a]pyrene. 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin‐induced ethoxyresorufin‐o‐deethylase activity was 2‐fold greater in human colon adenocarcinoma cells cultured on Matrigel compared to cells cultured on plastic. Extracellular matrix‐mediated differentiation and apoptosis of intestinal cells provide in vitro systems for study of the regulation of CYP1A1 expression, carcinogen activation in the gut and mechanism(s) of apoptosis of colon cancer cells. J. Cell. Biochem. 86: 440–450, 2002. © 2002 Wiley‐Liss, Inc.
Synergistic stimulation of MUC1 expression in normal breast epithelia and breast cancer cells by interferon‐γ and tumor necrosis factor‐α
Authors: Lagow Errin L. , Carson Daniel D. 
Published: October 2002

AbstractThe MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancers. Persistent stimulation by proinflammatory cytokines may contribute to increased MUC1 transcription by tumor cells. We demonstrate that MUC1 expression in T47D breast cancer cells and normal human mammary epithelial cells (HMEC) is enhanced by tumor necrosis factor‐α (TNF‐α) in the presence of interferon‐γ (IFN‐γ). MUC1 responsiveness to these cytokines was modest in T47D cells and robustly induced in HMEC. Transient transfection of T47D cells with mutant MUC1 promoter constructs revealed that a κB site at −589/−580 and the STAT‐binding element at −503/−495 and were required for cooperative stimulation by TNFα and IFN‐γ. Binding of NFκB p65 to the MUC1 κB site was induced by TNF‐α treatment, as demonstrated by electrophoretic mobility shift assay. Specific mutation of the κB site prevented binding of NFκB p65 and blocked TNF‐α stimulation of MUC1 promoter activity. Collectively, these studies demonstrate synergistic stimulation of MUC1 expression by TNF‐α and IFN‐γ that is mediated by independent actions of NFκB p65 and STAT1α upon κB and STAT sites, respectively, in the MUC1 promoter. Strong induction of MUC1 expression by these proinflammatory cytokines is clearly evident in normal mammary epithelium. In contrast, breast tumor cells appear to override normal regulatory responses via as yet undefined cis‐elements. J. Cell. Biochem. 86: 759–772, 2002. © 2002 Wiley‐Liss, Inc.
Biochemical and cellular characteristics of the four splice variants of protein kinase CK1α from zebrafish (Danio rerio)
Authors: Burzio Veronica , Antonelli Marcelo , Allende Catherine C. , Allende Jorge E. 
Published: October 2002

AbstractProtein kinase CK1 (previously known as casein kinase I) conforms to a subgroup of the great protein kinase family found in eukaryotic organisms. The CK1 subgroup of vertebrates contains seven members known as α, β, γ1, γ2, γ3, δ, and ε. The CK1α gene can generate four variants (CK1α, CK1αS, CK1αL, and CK1αLS) through alternate splicing, characterized by the presence or absence of two additional coding sequences. Exon “L” encodes a 28‐amino acid stretch that is inserted after lysine 152, in the center of the catalytic domain. The “S” insert encodes 12 amino acid residues and is located close to the carboxyl terminus of the protein. This work reports some biochemical and cellular properties of the four CK1α variants found to be expressed in zebrafish (Danio rerio). The results obtained indicate that the presence of the “L” insert affects several biochemical properties of CK1α: (a) it increases the apparent Km for ATP twofold, from ∼30 to ∼60 μM; (b) it decreases the sensitivity to the CKI‐7 inhibitor, raising the I50 values from 113 to ∼230 μM; (c) it greatly decreases the heat stability of the enzyme at 40°C. In addition, the insertion of the “L” fragment exerts very important effects on some cellular properties of the enzyme. CK1αL concentrates in the cell nucleus, excluding nucleoli, while the CK1α variant is predominantly cytoplasmic, although some presence is observed in the nucleus. This finding supports the thesis that the basic‐rich region found in the “L” insert acts as a nuclear localization signal. The “L” insert‐containing variant was also found to be more rapidly degraded (half‐life of 100 min) than the CK1α variant (half‐life of 400 min) in transfected Cos‐7 cells. J. Cell. Biochem. 86: 805–814, 2002. © 2002 Wiley‐Liss, Inc.
Sp1 and Sp3 activate the testis‐specific histone H1t promoter through the H1t/GC‐box
Authors: Wilkerson Donald C. , Wolfe Steven A. , Grimes Sidney R. 
Published: October 2002

AbstractThe testis‐specific linker histone H1t gene is transcribed exclusively in mid to late pachytene primary spermatocytes. Tissue specific expression of the gene is mediated in large part through elements located within the proximal promoter. Previous work in transgenic animals showed that a unique 40 bp promoter element designated H1t/TE is essential for spermatocyte‐specific expression. The H1t/TE element contains a GC‐box, which is a perfect consensus binding site for members of the Sp family of transcription factors. We have shown that Sp1 and Sp3 are present in testis cells from 9‐day‐old and adult rats and in pachytene primary spermatocytes and early spermatids and that they can bind to the H1t/GC‐box. Mutagenesis of the GC‐box reduced H1t promoter activity. Furthermore, a CpG dinucleotide within the GC‐box was totally unmethylated in rat testis primary spermatocytes where the gene is transcribed but it was methylated in liver where the gene is silenced. These previous studies supported the importance of the GC‐box and suggested that Sp transcription factors contribute to expression of the H1t gene. In this study, we show that co‐transfection of Sp1 and Sp3 expression vectors leads to an upregulation of histone H1t promoter activity in several cell lines including testis GC‐2spd cells. However, very low H1t promoter activity is seen in GC‐2spd cells grown at 39°C, which correlates with lower levels of Sp1 and Sp3 in these cells grown at this elevated temperature. Upregulation of the H1t promoter by Sp1 and Sp3 was also seen in cotransfected NIH3T3 and C127I cell lines. On the other hand, co‐transfection of the Sp1 and Sp3 expression vectors does not lead to upregulation of activity of the cell‐cycle dependent histone H1d promoter. J. Cell. Biochem. 86: 716–725, 2002. © 2002 Wiley‐Liss, Inc.
MM3 parametrization of four‐ and five‐coordinated rhenium complexes by a genetic algorithm—Which factors influence the optimization performance?
Authors: Strassner Thomas , Busold Markus , Herrmann Wolfgang A. 
Published: October 2002

AbstractGenetic algorithms (GA) were used to solve one of the multidimensional problems in computational chemistry, the optimization of force field parameters. The correlation between the composition of the GA, its parameters (pc,pm) and the quality of the results were investigated. The composition was studied for all combinations of a Simple GA/Steady State GA with a Roulette Wheel/Tournament Selector using different values each for crossover (0.5, 0.7, 0.9) and mutation rates (0.01, 0.02, 0.05, 0.10, 0.20). The results show that the performance is strongly dependent on the GA scheme, where the Simple GA/Tournament Selector yields the best results. Two new MM3 parameters were introduced for rhenium compounds with coordination number four (204) and coordination number five (205), the formal oxidation states of rhenium ranging from +V to +VII. A manifold of parameters (Re‐C, N, O, S) was obtained by using a diverse set of CSD structures. The advantage of the GA vs. UFF calculations is shown by comparison of several examples. The GA optimized parameters were able to reproduce the geometrical data of the X‐ray structures. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 282–290, 2002
Chemical shift driven geometry optimization
Authors: Witter Raiker , Prie Wolfram , Sternberg Ulrich 
Published: October 2002

AbstractA new method for refinement of 3D molecular structures by geometry optimization is presented. Prerequisites are a force field and a very fast procedure for the calculation of chemical shifts in every step of optimization. To the energy, provided by the force field (COSMOS force field), a pseudoenergy, depending on the difference between experimental and calculated chemical shifts, is added. In addition to the energy gradients, pseudoforces are computed. This requires the derivatives of the chemical shifts with respect to the coordinates. The pseudoforces are analytically derived from the integral expressions of the bond polarization theory. Single chemical shift values attributed to corresponding atoms are considered for structural correction. As a first example, this method is applied for proton position refinement of the D‐mannitol X‐ray structure. A crystal structure refinement with 13C chemical shift pseudoforces is carried out. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 298–305, 2002
Efficient linear algebra routines for symmetric matrices stored in packed form
Authors: Ahlrichs Reinhart , Tsereteli Kakha 
Published: October 2002

AbstractQuantum chemistry methods require various linear algebra routines for symmetric matrices, for example, diagonalization or Cholesky decomposition for positive matrices. We present a small set of these basic routines that are efficient and minimize memory requirements. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 306–309, 2002
Binding of D‐ and L‐captopril inhibitors to metallo‐β‐lactamase studied by polarizable molecular mechanics and quantum mechanics
Authors: Antony Jens , Gresh Nohad , Olsen Lars , Hemmingsen Lars , Schofield Christopher J. , Bauer Rogert 
Published: October 2002

AbstractThe bacterial Zn2+ metallo‐β‐lactamase from B. fragilis is a zinc‐enzyme with two potential metal ion binding sites. It cleaves the lactam ring of antibiotics, thus contributing to the acquired resistance of bacteria against antibiotics. The present study bears on the binuclear form of the enzyme. We compare several possible binding modes of captopril, a mercaptocarboxamide inhibitor of several zinc‐metalloenzymes. Two diastereoisomers of captopril were considered, with either a D‐ or an L‐proline residue. We have used the polarizable molecular mechanics procedure SIBFA (Sum of Interactions Between Fragments ab initio computed). Two β‐lactamase models were considered, encompassing 104 and 188 residues, respectively. The energy balances included the inter and intramolecular interaction energies as well as the contribution from solvation computed using a continuum reaction field procedure. The thiolate ion of the inhibitor is binding to both metal ions, expelling the bridging solvent molecule from the uncomplexed enzyme. Different competing binding modes of captopril were considered, either where the inhibitor binds in a monodentate mode to the zinc cations only with its thiolate ion, or in bidentate modes involving additional zinc binding by its carboxylate or ketone carbonyl groups. The additional coordination by the inhibitor's carboxylate or carbonyl group always occurs at the zinc ion, which is bound by a histidine, a cysteine, and an aspartate side chain. For both diastereomers, the energy balances favor monodentate binding of captopril via S−. The preference over bidentate binding is small. The interaction energies were recomputed in model sites restricted to captopril, the Zn2+ cations, and their coordinating end side chains from β‐lactamase (98 atoms). The interaction energies and their ranking among competing arrangements were consistent with those computed by ab initio HF and DFT procedures. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1281–1296, 2002
Combined ab initio/empirical approach for optimization of Lennard‐Jones parameters for polar‐neutral compounds
Authors: Chen I Jen , Yin Daxu , MacKerell Alexander D. 
Published: October 2002

AbstractThe study of small functionalized organic molecules in aqueous solution is a useful step toward gaining a basic understanding of the behavior of biomolecular systems in their native aqueous environment. Interest in studying amines and fluorine‐substituted compounds has risen from their intrinsic physicochemical properties and their prevalence in biological and pharmaceutical compounds. In the present study, a previously developed approach which optimizes Lennard‐Jones (LJ) parameters via the use of rare gas atoms combined with the reproduction of experimental condensed phase properties was extended to polar–neutral compounds. Compounds studied included four amines (ammonia, methylamine, dimethylamine, and trimethylamine) and three fluoroethanes (1‐fluoroethane, 1,1‐difluoroethane, and 1,1,1‐trifluoroethane). The resulting force field yielded heats of vaporization and molecular volumes in excellent agreement with the experiment, with average differences less than 1%. The current amine CHARMM parameters successfully reproduced experimental aqueous solvation data where methylamine is more hydrophilic than ammonia, with hydrophobicity increasing with additional methylation on the nitrogen. For both the amines and fluoroethanes the parabolic relationship of the extent of methylation or fluorination, respectively, to the heats of vaporization were reproduced by the new parameters. The present results are also discussed with respect to the impact of parameterization approach to molecular details obtained from computer simulations and to the unique biological properties of fluorine in pharmaceutical compounds. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 199–213, 2002