bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear‐cytoplasmic transport of EGFR involves receptor endocytosis, importin β1 and CRM1
Authors: Lo Hui‐Wen , Ali‐Seyed Mohamed , Wu Yadi , Bartholomeusz Geoffrey , Hsu Sheng‐Chieh , Hung Mien‐Chie 
Published: March 2006

AbstractMany receptor tyrosine kinases (RTKs) can be detected in the cell nucleus, such as EGFR, HER‐2, HER‐3, HER‐4, and fibroblast growth factor receptor. EGFR, HER‐2 and HER‐4 contain transactivational activity and function as transcription co‐factors to activate gene promoters. High EGFR in tumor nuclei correlates with increased tumor proliferation and poor survival in cancer patients. However, the mechanism by which cell‐surface EGFR translocates into the cell nucleus remains largely unknown. Here, we found that EGFR co‐localizes and interacts with importins α1/β1, carriers that are critical for macromolecules nuclear import. EGFR variant mutated at the nuclear localization signal (NLS) is defective in associating with importins and in entering the nuclei indicating that EGFR's NLS is critical for EGFR/importins interaction and EGFR nuclear import. Moreover, disruption of receptor internalization process using chemicals and forced expression of dominant‐negative Dynamin II mutant suppressed nuclear entry of EGFR. Additional evidences suggest an involvement of endosomal sorting machinery in EGFR nuclear translocalization. Finally, we found that nuclear export of EGFR may involve CRM1 exportin as we detected EGFR/CRM1 interaction and markedly increased nuclear EGFR following exposure to leptomycin B, a CRM1 inhibitor. Collectively, these data suggest the importance of receptor endocytosis, endosomal sorting machinery, interaction with importins α1/β1, and exportin CRM1 in EGFR nuclear‐cytoplasmic trafficking. Together, our work sheds light into the nature and regulation of the nuclear EGFR pathway and provides a plausible mechanism by which cells shuttle cell‐surface EGFR and potentially other RTKs through the nuclear pore complex and into the nuclear compartment. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Identification of regions of leukotriene C4 synthase which direct the enzyme to its nuclear envelope localization
Authors: Svartz Jesper , Hallin Elisabeth , Shi Yixuan , Söderström Mats , Hammarström Sven 
Published: March 2006

AbstractLeukotrienes (LTs) are fatty acid derivatives formed by oxygenation of arachidonic acid via the 5‐lipoxygenase (5‐LO) pathway. Upon activation of inflammatory cells 5‐LO is translocated to the nuclear envelope (NE) where it converts arachidonic acid to the unstable epoxide LTA4. LTA4 is further converted to LTC4 by conjugation with glutathione, a reaction catalyzed by the integral membrane protein LTC4 synthase (LTC4S), which is localized on the NE and endoplasmic reticulum (ER). We now report the mapping of regions of LTC4S that are important for its subcellular localization. Multiple constructs encoding fusion proteins of green fluorescent protein (GFP) as the N‐terminal part and various truncated variants of human LTC4S as C‐terminal part were prepared and transfected into HEK 293/T or COS‐7 cells. Constructs encoding hydrophobic region 1 of LTC4S (amino acids 6–27) did not give distinct membrane localized fluorescence. In contrast hydrophobic region 2 (amino acids 60–89) gave a localization pattern similar to that of full length LTC4S. Hydrophobic region 3 (amino acids 114–135) directed GFP to a localization indistinguishable from that of full length LTC4S. A minimal directing sequence, amino acids 117–132, was identified by further truncation. The involvement of the hydrophobic regions in the homo‐oligomerization of LTC4S was investigated using bioluminescence resonance energy transfer (BRET) analysis in living cells. BRET data showed that hydrophobic regions 1 and 3 each allowed oligomerization to occur. These regions most likely form transmembrane helices, suggesting that homo‐oligomerization of LTC4S is due to helix–helix interactions in the membrane. J. Cell. Biochem. 98: 1517–1527, 2006. © 2006 Wiley‐Liss, Inc.
Low molecular weight polyethylenimines linked by β‐cyclodextrin for gene transfer into the nervous system
Authors: Tang G. P. , Guo H. Y. , Alexis F. , Wang X. , Zeng S. , Lim T. M. , Ding J. , Yang Y. Y. , Wang S. 
Published: March 2006

AbstractBackgroundPolyethylenimines (PEIs) with high molecular weights are effective nonviral gene delivery vectors. However, the in vivo use of these PEIs can be hampered by their cellular toxicity. In the present study we developed and tested a new PEI polymer synthesized by linking less toxic, low molecular weight (MW) PEIs with a commonly used, biocompatible drug carrier, β‐cyclodextrin (CyD).Methods and resultsThe terminal CyD hydroxyl groups were activated by 1,1′‐carbonyldiimidazole. Each activated CyD then linked two branched PEI molecules with MW of 600 Da to form a CyD‐containing polymer with MW of 61 kDa, in which CyD served as a part of the backbone. The PEI‐CyD polymer developed was soluble in water and biodegradable. In cell viability assays with sensitive neurons, the polymer performed similarly to low‐MW PEIs and displayed much lower cellular cytotoxicity compared to PEI 25 kDa. The gene delivery efficiency of the polymer was comparable to, and at higher polymer/DNA ratios even higher than, that offered by PEI 25 kDa in neural cells. Attractively, intrathecal injection of plasmid DNA complexed by the polymer into the rat spinal cord provided levels of gene expression close to that offered by PEI 25 kDa.ConclusionsThe polymer reported in the current study displayed improved biocompatibility over non‐degradable PEI 25 kDa and mediated gene transfection in cultured neurons and in the central nervous system effectively. The new polymer would be worth exploring further as an in vivo delivery system of therapeutic genetic materials for gene therapy of neurological disorders. Copyright © 2006 John Wiley & Sons, Ltd.
Impact of immobilized polysaccharide chiral stationary phases on enantiomeric separations
Authors: Ali Imran , Aboul‐Enein Hassan Y. 
Published: March 2006

AbstractImmobilized polysaccharide‐based chiral stationary phases (CSPs) are gaining importance in the resolution of racemic compounds due to their stable nature on working with normal solvents and those prohibited for use with coated phases (tetrahydrofuran, chloroform, dichloromethane, acetone, 1,4‐dioxane, ethyl acetate, and certain other ethers). This review discusses the use of immobilized polysaccharide CSPs in the chiral resolution of various racemates by liquid chromatography. The discussion includes immobilization methodologies, enantioselectivities, efficiencies, and a comparison of chiral recognition capabilities of coated vs. immobilized CSPs. Some applications of immobilized CSPs to the chiral resolution of racemic compounds are also presented.
Changes in the pore character of silicas caused by surface bonding and polymer coating
Authors: Hayrapetyan Sergey S. , Neue Uwe D. , Khachatryan Hambardzum G. 
Published: March 2006

AbstractThe pore character of packings for liquid chromatography, especially reversed‐phase (RPLC) packings, has been studied by means of the nitrogen adsorption method (BET method). Micro‐spherical silica gels with 9, 12, 30, 40 and 50 nm average pore diameter have been used as carriers. These silica gels have been modified with monochlorodimethyloctadecylsilane and several polymers (polyoctadecylmethacrylate‐methylmethacrylate co‐polymer, polyacrylamide gel, polyvinyl alcohol, poly‐2‐hydroxyethylmethacrylate). A larger decrease in the specific surface area values was observed in the case of the polymer coating with the polyoctadecylmethacrylate‐methylmethacrylate co‐polymer compared with the derivatization by silanes or the modification with polymers without C18‐groups. A new approach has been suggested to explain some questions concerning the interpretation of the data obtained during the measurements of the pore characteristics of the derivatized packings. An attempt has been made to reveal peculiarities connecting values of the measured surface of RP‐packings with the specific surface area values of the initial silica, as well as with the chromatographically accessible surface.
A detailed discussion of the influence of the amount of deposited polymer on the retention properties of polymer‐coated silicas
Authors: Hayrapetyan Sergey S. , Khachatryan Hambardzum G. , Neue Uwe D. 
Published: March 2006

AbstractProblems of the modification of the surface of micro‐spherical silica gel with layers of polymer and the influence of the quantity of the coated polymer on the chromatographic properties of the resulting sorbents have been considered. The polymer modification of the surface of wide‐pore micro‐spherical silica gel obtained by means of hydrothermal treatment of the meso‐porous silica gel under autoclave conditions is described. The polymer layer itself is formed by an octadecylmethacrylate‐methylmethacrylate co‐polymer. As a result, packings for RP‐HPLC were obtained. An increase of the capacity factor (k) has been observed with an increase of the quantity of the polymer deposited during the polymer modification process. The indicated phenomenon depends on the increase of the number of C18 groups in the packing.
Applicability of alkyl‐bonded ultra‐pure silica stationary phases for gradient reversed‐phase HPLC of folates with conventional and volatile buffers under highly aqueous conditions
Authors: Patring Johan D. M. , Lanina Svetlana A. , Jastrebova Jelena A. 
Published: March 2006

AbstractApplicability of several alkyl‐bonded silica stationary phases was tested for gradient RP‐HPLC of folates under highly aqueous conditions. High retention of folates was achieved on alternative phases with enhanced polarity and classical phases with higher carbon content. Phases exhibiting polar secondary interactions were found to provide better selectivity for late‐eluting folates, whereas selectivity for early‐eluting folates was mostly dependent on hydrophobic interactions. Best selectivity in phosphate buffered mobile phase was achieved on polar‐endcapped silica phases (Aquasil C18 and HyPurity Aquastar) followed by alternative Atlantis dC18. Classical phases exhibited poorer separation of 10‐formyl‐folic acid and 5‐formyl‐tetrahydrofolate, but it could be considerably improved by increasing the buffer pH. Strong secondary interactions of ion‐exchange character on polar‐embedded phases resulted in marked peak deterioration, loss of recovery and dramatic changes in retention behaviour for early‐ and late‐eluting folates when changing the mobile phase composition and pH. Therefore, polar‐embedded phases such as HyPurity Advance were found to be unsuitable for separating folates. Stationary phases exhibited peak deterioration when using volatile buffer of low ionic strength. Better results were obtained with classical phases, whereas alternative phases showed not only peak deterioration but also a decrease in recovery and poorer selectivity due to increased secondary interactions in volatile buffer.
Enantioseparation using alkoxyphenylcarbamates of cellulose and amylose as chiral stationary phase for high‐performance liquid chromatography
Authors: Yamamoto Chiyo , Inagaki Shinji , Okamoto Yoshio 
Published: March 2006

AbstractCellulose and amylose phenylcarbamates having one or two alkoxy groups on a phenyl ring were synthesized, and their chiral recognition abilities as chiral stationary phases for HPLC were evaluated. Compared to the 4‐methoxyphenylcarbamates of cellulose and amylose, which are known to show a poor chiral recognition, the 3‐methoxyphenylcarbamates exhibited much higher chiral recognitions. For cellulose derivatives, as the bulkiness of the 3‐alkoxy group increased, the chiral recognition ability increased. On the other hand, for the amylose derivatives, a clear relation between the chiral recognition and the bulkiness of the alkoxy group was not observed, and the 3‐methoxy, ethoxy, and isopropoxyphenylcarbamates showed relatively high chiral recognitions. The introduction of two methoxy groups to the meta‐positions decreased the chiral recognition ability. In order to discuss the relationship between the structure and chiral recognition ability of the alkoxyphenylcarbamates, their molecular models were constructed.
Altered gene expression in Opisthorchis viverrini‐associated cholangiocarcinoma in hamster model
Authors: Loilome Watcharin , Yongvanit Puangrat , Wongkham Chaisiri , Tepsiri Nisana , Sripa Banchob , Sithithaworn Paiboon , Hanai Shuji , Miwa Masanao 
Published: March 2006

AbstractCholangiocarcinoma (CCA) induced by liver fluke (Opisthorchis viverrini, Ov) infection is one of the most common and serious disease in northeast Thailand. To elucidate the molecular mechanism of cholangiocarcinogenesis induced by Ov infection, we employed a hamster model of CCA induced by Ov and N‐nitrosodimethylamine and analyzed candidate genes involved in CCA using fluorescence differential display‐PCR. Of 149 differentially amplified bands we identified, the upregulation of 23 transcripts and downregulation of 1 transcript related to CCA hamsters were confirmed by a reverse northern macroarray blot. The upregulated genes include signal transduction protein kinase A regulatory subunit Iα (Prkar1a), myristoylated alanine‐rich protein kinase C substrate, transcriptional factor LIM‐4‐only domain, oxysterol‐binding protein involved in lipid metabolism, splicing regulatory protein 9, ubiquitin conjugating enzyme involved in protein degradation, β tubulin, β actin, and collagen type VI. Quantitative real‐time PCR confirmed that the expression of Prkar1a was significantly higher in CCA and its precursor lesion when compared with normal liver and normal gall bladder epithelia (P < 0.05). Prkar1a expression tended to increase along with the progression of biliary transformation from hyperplasia and precancerous lesions to carcinoma. These findings contribute to our understanding of the processes involved in the molecular carcinogenesis of CCA in order to provide a unique perspective on the development of new chemotherapeutics in future. © 2006 Wiley‐Liss, Inc.
Cooperative inhibitory effect of ZD1839 (Iressa) in combination with 17‐AAG on glioma cell growth
Authors: Premkumar Daniel R. , Arnold Beth , Pollack Ian F. 
Published: March 2006

AbstractZD1839 (“Iressa”) is an orally active, selective epidermal growth factor (EGF) receptor‐tyrosine kinase inhibitor. We evaluated the antitumor activity of ZD1839 in combination with HSP90 antagonist, 17‐AAG in malignant human glioma cell lines. ZD1839 independently produced a dose‐dependent inhibition of cellular proliferation in glioma cells grown in culture with time‐ and dose‐dependent accumulation of cells in G1 phase of the cell cycle on flow cytometric analysis, although the concentrations required for optimal efficacy were at or above the limits of clinically achievable levels. Because the heat shock protein (HSP) is involved in the conformational maturation of a number of signaling proteins critical to the proliferation of malignant glioma cells, we hypothesized that the HSP90 inhibitor 17‐AAG would potentiate ZD 1839‐mediated glioma cytotoxicity by decreasing the activation status of EGF receptor, as well as downregulating the levels of other relevant signaling effectors. We, therefore, examined the effects of ZD1839 and 17‐AAG, alone and in combination, on signal transduction and apoptosis in a series of malignant glioma cell lines. Simultaneous exposure to these inhibitors significantly induced cell death and quantitative analysis revealed that interaction between ZD1839 and 17‐AAG‐induced cytotoxicity was synergistic, leading to a pronounced increase in active caspase‐3 and PARP cleavage. No significant growth inhibition or caspase activation was seen in control cells. The enhanced cytotoxicity of this combination was associated with diminished Akt activation and a significant downregulation of EGFR receptor, Raf‐1 and mitogen activated protein kinase (MAPK). Cells exposed to 17‐AAG and ZD1839 displayed a significant reduction in cell cycle regulatory proteins, such as CDK4 and CDK6. Taken together, these findings suggest that ZD1839, an EGF receptor tyrosine kinase inhibitor, plays a critical role in regulating the apoptotic response to 17‐AAG and that multi‐site targeting of growth signaling and cell survival pathways could provide a potent strategy to treat patients with malignant gliomas. © 2006 Wiley‐Liss, Inc.
Coronoidotomy as treatment for trismus due to jaw‐closing oromandibular dystonia
Authors: Yoshida Kazuya 
Published: March 2006

AbstractOromandibular dystonia is a focal dystonia involving the masticatory and/or tongue muscles. This report describes 2 female patients with jaw‐closing dystonia treated by surgical resection of the coronoid process. The patients could not open their mouths due to involuntary jaw‐closing muscle contraction. We first treated them by injecting lidocaine and alcohol (muscle afferent block) into the masseter and temporal muscles and then botulinum toxin. However, the trismus improved mildly and transitorily. Therefore, coronoidotomy was done under general anesthesia. The jaw opening increased to 50 mm. Coronoidotomy is useful for patients with jaw‐closing dystonia in whom other therapies are ineffective. © 2006 Movement Disorder Society
Association of the Tau haplotype with Parkinson's disease in the Greek population
Authors: Fidani Liana , Kalinderi Kallirhoe , Bostantjopoulou Sevasti , Clarimon Jordi , Goulas Antonis , Katsarou Zoe , Hardy John , Kotsis Alexandros 
Published: March 2006

AbstractWe compared the distribution of the Tau H1 haplotype and related subhaplotypes in a group of clinically diagnosed Parkinson's disease patients (n = 133) and in control individuals (n = 113) from northern Greece. We were able to detect a statistically significant overrepresentation of the H1H1 genotype in our patient group (OR for H1H1 vs. H1H2 and H2H2: 1.73; 95% CI: 1.03–2.90; P = 0.037). The H1 subhaplotype significantly associated with the disease in our population was different from the one previously reported for a Norwegian population, suggesting that the nature of the association of Tau with Parkinson's disease is influenced by ethnic variation. © 2006 Movement Disorder Society
A pulsed field gradient NMR diffusion investigation of enkephalin peptide‐sodium dodecyl sulfate micelle association
Authors: Begotka Brandon A. , Hunsader Jennifer L. , Oparaeche Chinelo , Vincent Jonathan K. , Morris Kevin F. 
Published: March 2006

AbstractPulsed field gradient NMR (PFG‐NMR) diffusion experiments were used to investigate the binding of leucine and methionine enkephalin peptides to anionic sodium dodecyl sulfate (SDS) micelles. The study was undertaken to investigate the mechanism of interaction between enkephalin peptides and SDS micelles and to determine if NMR‐derived association constants, Keq, can predict the elution order in electrokinetic chromatography (EKC). In EKC, peptides are separated on the basis of their interactions with micelles. The Leu‐enkephalin peptide–micelle association constant increased from 130 ± 8 to 1459 ± 57 and 1744 ± 64 M−1, respectively, when an Arg or Lys was added to the C‐terminus. The association constant of Leu‐enkephalinamide was approximately equal to that of Leu‐enkephalin‐Arg. Substitution of Phe4 with a Trp or Gly2 with an Ala in the Leu‐enkephalin peptides also increased the micelle binding affinity. These results confirm that the interaction of Leu‐enkephalin peptides with SDS micelles is largely electrostatic and that the non‐polar amino acid side chains interact with the hydrophobic micelle core. The peptide–micelle association constants for the cationic Met‐enkephalin peptides were also greater than their zwitterionic counterparts. For example, the Met‐enkephalin Keq value was 162 ± 9 M−1, while the association constants for Met‐enkephalin‐Arg, Met‐enkephalin‐Lys, and Met‐enkephalinamide were, respectively, 674 ± 31, 426 ± 23, and 453 ± 27 M−1. In both Met‐enkephalin and Met‐enkephalinamide, replacing Gly2 with an Ala did not significantly increase the association constant. These results confirm that with the Met‐enkephalin peptides, there was little or no interaction of the amino acid side chains with the micelle core. For both the Leu‐enkephalin and Met‐enkephalin peptides, the association constants were consistent with EKC results, in that the peptides with smaller Keq values were found to elute before those with larger association constants. Copyright © 2006 John Wiley & Sons, Ltd.
Therapeutic implications of the specific inhibition of causative matrix metalloproteinases in experimental colitis induced by dextran sulphate sodium
Authors: Kobayashi K , Arimura Y , Goto A , Okahara S , Endo T , Shinomura Y , Imai K 
Published: March 2006

AbstractExtracellular matrix dynamics, crucial for tissue remodelling, are highly regulated by a cascade of matrix metalloproteinases (MMPs) during inflammation and wound healing processes in inflammatory bowel disease (IBD). Contrary to expectations, there are limited reports to date that MMP inhibitors have some beneficial therapeutic effects in experimental colitis models. Furthermore, clinical trials of MMP inhibitors against certain tumours have failed to show any therapeutic benefit. One major reason for this lack of success may be the apparent uncertainty about the precise spectrum of inhibitory activity required. Since tumour necrosis factor alpha (TNFα), a key mediator in colonic inflammation, promotes MMP production in a dose‐dependent manner, the therapeutic success of anti‐TNFα agents against IBD motivated us to re‐evaluate the therapeutic potential of MMP inhibition. First, using a quantitative polymerase chain reaction (PCR), western blotting, and zymography, we determined which MMPs were relevant to experimental colitis induced in mice by dextran sulphate sodium. Next, we examined a distinct role for MAPK and NFκB signalling pathways in the regulation of the expression of these MMP genes. Finally, we examined whether transcriptional regulation of these MMPs, either indirectly using inhibitors of MAPK and/or NFκB signalling pathways or directly using siRNA directed against these MMPs, contributes to the prevention of colitis. Changes in the expression level of colonic MMP‐3 and MMP‐10 preceded the clinical course of colitis. Colitis improved in mice that received these signal inhibitors, together with suppression of MMP expression. Moreover, siRNA that targeted MMP‐3 and MMP‐10 effectively reduced both the transcription of these MMPs and the severity of colitis. We conclude that MMP‐3 and MMP‐10 play a causal role in excess tissue destruction in colitis. Specific inhibition of these MMPs should provide novel therapeutics against IBD. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Glass transition and crystallization kinetics of Sb14.5As29.5Se53.5Te2.5 amorphous solid
Authors: Othman A. A. , Aly K. A. , Abousehly A. M. 
Published: March 2006

AbstractThe crystallization kinetics of the quaternary Sb14.5As29.5Se53.5Te2.5 glassy alloy was studied under non‐isothermal conditions. The method was applied to the experimental data obtained by differential scanning calorimetry (DSC), using continuous‐heating techniques. In addition, two approaches are used to analyze the dependence of glass transition temperature (T g) on the heating rate (β ). One is empirical linear relationship between (T g) and ln (β ). The other approach is the use of straight line ln ($ T^2_{\rm g} $/β ) vs. 1/T g for evaluation of the activation energy for glass transition. The phases at which the alloy crystallizes after the thermal process have been identified by X‐ray diffraction. The diffractogram of the transformed material shows the presence of some crystallites of As, SbTe, AsSb, As2Se3, Sb2Se3 and AsSe5Te5 in the residual amorphous matrix. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)