bluuebunny/crossref_metadata_2025 huggingface dataset:
Postsurgical chemotherapy in stage IB nonsmall cell lung cancer: Long‐term survival in a randomized study
Authors: Roselli Mario , Mariotti Sabrina , Ferroni Patrizia , Laudisi Anastasia , Mineo Davide , Pompeo Eugenio , Ambrogi Vincenzo , Mineo Tommaso C.
Published: March 2006

Although surgical resection is considered the adequate treatment in early stages of nonsmall cell lung cancer, long‐term survival is not satisfactory and recurrence rate is high. We previously showed that postoperative chemotherapy at stage IB reduces recurrences and prolongs overall survival. We extended size and observation period of the study sample and performed a separate analysis for minimally resected patients. The trial was designed as a randomized, 2‐armed study with postoperative adjuvant chemotherapyversussurgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure (defined as anatomical or minimal). Chemotherapy consisted of cisplatin (100 mg/m2day 1) and etoposide (120 mg/m2days 1–3) for 6 cycles. The primary endpoint was overall survival; secondary endpoint was disease‐free survival (DFS). One hundred and forty patients entered the study: 70 were assigned to the adjuvant chemotherapy group and 70 to the control group. Groups were homogeneous for conventional risk factors. There was no clinically significant morbidity associated to chemotherapy. Patients were followed for a mean period of 40.31 ± 30.86 months. A significant difference in overall (p= 0.02) and disease‐free (p= 0.0001) survival was observed between patients undergoing adjuvant chemotherapyvs.control group. Adjuvant chemotherapy significantly improved both overall (p= 0.02) and DFS (p= 0.003) of anatomically resected patients, but only the DFS (p= 0.02) of minimally resected patients. Our results confirm that adjuvant chemotherapy may have a real impact on long‐term survival in patients with stage IB nonsmall cell lung cancer being this effect especially evident for those anatomically resected. © 2006 Wiley‐Liss, Inc.
The histone deacetylase inhibitor, suberoylanilide hydroxamic acid, overcomes resistance of human breast cancer cells to Apo2L/TRAIL
Authors: Butler Lisa M. , Liapis Vasilios , Bouralexis Stelios , Welldon Katie , Hay Shelley , Thai Le M. , Labrinidis Agatha , Tilley Wayne D. , Findlay David M. , Evdokiou Andreas
Published: March 2006

While the apoptosis‐inducing ligand Apo2L/TRAIL is a promising new agent for the treatment of cancer, the sensitivity of cancer cells for induction of apoptosis by Apo2L/TRAIL varies considerably. Identification of agents that can be used in combination with Apo2L/TRAIL to enhance apoptosis in breast cancer cells would increase the potential utility of this agent as a breast cancer therapeutic. Here, we show that the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), can sensitize Apo2L/TRAIL‐resistant breast cancer cells to Apo2L/TRAIL‐induced apoptosis. Importantly, neither Apo2L/TRAIL alone, nor in combination with SAHA, affected the viability of normal human cells in culture. Apo2L/TRAIL‐resistant MDA‐MB‐231 breast cancer cells, generated by long‐term culture in the continuous presence of Apo2L/TRAIL, were resensitized to Apo2L/TRAIL‐induced apoptosis by SAHA. The sensitization of these cells by SAHA was accompanied by activation of caspase 8, caspase 9 and caspase 3 and was concomitant with Bid and PARP cleavage. The expression of the proapoptotic protein, Bax, increased significantly with SAHA treatment and high levels of Bax were maintained in the combined treatment with Apo2L/TRAIL. Treatment with SAHA increased cell surface expression of DR5 but not DR4. Interestingly, SAHA treatment also resulted in a significant increase in cell surface expression of DcR1. Taken together, our findings indicate that the use of these 2 agents in combination may be effective for the treatment of breast cancer. © 2006 Wiley‐Liss, Inc.
Enhanced EGR1 activity promotes the growth of prostate cancer cells in an androgen‐depleted environment
Authors: Yang Shan‐Zhong , Eltoum Isam A. , Abdulkadir Sarki A.
Published: March 2006

During anti‐hormonal therapy for prostate cancer, a major clinical problem is the development of androgen‐independent disease. The molecular mechanisms underlying the transition to androgen independence are the subject of intense investigation. In many prostate tumors, the activity of the transcription factor EGR1 (early growth response gene 1) is elevated due to overexpression of EGR1 and/or downregulation of the co‐repressor, NAB2. We have modeled these alterations by expressing active EGR1 that does not bind NAB co‐repressor proteins in human prostate carcinoma cells. We show here that active EGR1 expression enhances the androgen‐independent growth of prostate carcinoma cells in vitro and in vivo. Employing RNAi and expression analyses, we show that EGR1 mediates its effects, at least in part, through the AR signaling pathway. These findings support a role for enhanced EGR1 activity in regulating the transition from androgen‐dependent to androgen‐independent prostate cancer. J. Cell. Biochem. 97: 1292–1299, 2006. © 2005 Wiley‐Liss, Inc.
Ghrelin stimulates interleukin‐8 gene expression through protein kinase C‐mediated NF‐κB pathway in human colonic epithelial cells
Authors: Zhao Dezheng , Zhan Yanai , Zeng Huiyan , Moyer Mary P. , Mantzoros Christos S. , Pothoulakis Charalabos
Published: March 2006

Ghrelin, a newly identified gastric peptide, is known for its potent activity in growth hormone (GH) release and appetite. Although ghrelin is involved in several other responses such as stress and intestinal motility, its potential role in intestinal inflammation is not clear. Here, we show that expression of ghrelin and its receptor mRNA is significantly increased during acute experimental colitis in mice injected intracolonically with trinitrobenzene sulfate (TNBS). We found by PCR that ghrelin receptor mRNA is expressed in non‐transformed human colonic epithelial NCM460 cells. Exposure of NCM460 cells stably transfected with ghrelin receptor mRNA to ghrelin, increased IκBα phosphorylation and its subsequent degradation. In addition, ghrelin stimulated NF‐κB‐binding activity and NF‐κB p65 subunit phosphorylation, and induced IL‐8 promoter activity and IL‐8 protein secretion. Furthermore, our data show that ghrelin‐induced IκBα and p65 phosphorylation was markedly reduced by pharmacological inhibitors of intracellular calcium mobilization (BAPTA/AM) and protein kinase C (GF 109203X). Pretreatment with BAPTA/AM or GF109203X also significantly attenuated ghrelin‐induced IL‐8 production. Together, our results strongly suggest that ghrelin may be a proinflammatory peptide in the colon. Ghrelin may participate in the pathophysiology of colonic inflammation by inducing PKC‐dependent NF‐κB activation and IL‐8 production at the colonocyte level. J. Cell. Biochem. 97: 1317–1327, 2006. © 2005 Wiley‐Liss, Inc.
Comparative proteomic analysis of apoptosis induced by sodium selenite in human acute promyelocytic leukemia NB4 cells
Authors: Dong Hua , Ying Tianyi , Li Ting , Cao Tingming , Wang Junjun , Yuan Jing , Feng Erling , Han Bingshe , Hua Fangyuan , Yang Yang , Yuan Jiangang , Wang Hengliang , Xu Caimin
Published: March 2006

Selenium (Se) is an essential trace element possessing anticarcinogenic properties. Sodium selenite (Na2SeO3) induced apoptosis in human acute promyelocytic leukemia (APL) cell line NB4 with dose and time dependency. In this study, proteomic techniques were used to study the apoptosis of NB4 cells induced by sodium selenite. Twenty‐six downregulated and four upregulated proteins were identified, which exhibited a 1.5‐fold change or greater. The identified proteins included key regulators of signal transduction such as Rho GDP dissociation inhibitor (Rho GDI) alpha and beta members of the MAPK family, and proteins involved in the regulation of c‐fos or c‐myc expression. Importantly, the identified proteins, hnRNP D0B and Rho GDI beta, which were related with the regulation of c‐myc, c‐fos, and c‐jun, were determined by reverse transcription‐polymerase chain reaction (RT‐PCR) to confirm their downregulation in proteomic study. Western blot analysis and RT‐PCR were then performed on three associated proteins: c‐Myc, c‐Fos, and c‐Jun, and their expression were observed to be significantly downregulated. Results showed that certain regulation involved in c‐myc, c‐fos, and c‐jun was present in the apoptosis, and the c‐Myc dependent‐on and Jun N‐terminal kinase (JNK) pathway also play roles. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Splice variant 3, but not 2 of receptor protein‐tyrosine phosphatase σ can mediate stimulation of insulin‐secretion by α‐latrotoxin
Authors: Lajus Sophie , Lang Jochen
Published: March 2006

α‐latrotoxin (α‐LTX) binds to several cell surface receptors including receptor protein‐tyrosine phosphatase σ (RPTPσ). Here we demonstrate that transient overexpression of the short splice variant 3 conferred α‐LTX induced secretion to hamster insulinoma (HIT‐15) cells. In contrast, the long splice variant 2 containing four additional extracellular fibronectin‐III domains was inactive in secretion or in a single cell assay. Toxin‐sensitive (MIN6) and toxin‐insensitive (HIT‐T15) insulinoma cell lines as well as PC12 cells expressed similar amounts of endogenous short RPTPσ splice variant suggesting that this receptor does not play a role for toxin‐sensitivity. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
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

Many 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

Leukotrienes (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

Background

Polyethylenimines (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 results

The 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.

Conclusions

The 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

Immobilized 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

The 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

Problems 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

Applicability 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

Cellulose 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

Cholangiocarcinoma (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

ZD1839 (“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

Oromandibular 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

We 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

Pulsed 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

Extracellular 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

The 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)
Temperature and magnetic field dependence of radiation‐induced magnetoresistance oscillations in a 2D electron gas
Authors: Iñarrea J. , Platero G.
Published: March 2006

A theoretical model is presented in which the existence of radiation‐induced zero‐resistance states is analyzed. An exact solution for the harmonic oscillator wave function in the presence of radiation, and a perturbation treatment for elastic scattering due to randomly distributed charged impurities, form the foundations of our model. Following this model most experimental results are reproduced. The existence of zero‐resistance states is thus explained in terms of the interplay of the electron MW‐driven orbit dynamics and the Pauli exclusion principle. In order to explain the strong temperature dependence of the longitudinal resistivity and the thermally activated transport in 2DEG, we present also a model based on the damping suffered by the microwave‐driven electronic orbit dynamics by interactions with the lattice ions yielding acoustic phonons. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Computational study of some benzamidine‐based inhibitors of thrombin‐like snake venom proteinases
Authors: Henriques Elsa S. , Nascimento Marco A. C. , Ramos Maria João
Published: March 2006

Pit viper venoms contain a number of serine proteinases that, despite their observed coagulant thrombin‐like action in vitro, exhibit a paradoxical benign defibrinogenating (anticoagulant) action in vivo, with clinical applications in preventing thrombi and improved blood circulation. Considering that several benzamidine‐based inhibitors, some highly selective to thrombin, also inhibit the enzymatic activity of such venombins, the modeling of their enzyme–inhibitor interactions could provide valuable information on the topological factors that determine the divergences in activity. The first step, and the object of the present study, was to derive the necessary set of parameters, consistent with the CHARMM force field, and to perform molecular dynamics (MD) simulations on a few selected representatives of the inhibitors in question under physiological conditions. Bonding and van der Waals parameters were derived by analogy to similar ones in the existing force field. Net atomic charges were obtained with a restrained fitting to the molecular electrostatic potential generated at B3LYP/6‐31G(d) level. The parameters were refined to reproduce the available experimental geometries and crystal data, and the MD simulations of the free inhibitors in aqueous solution at 298 K provided an insightful description of their available conformational space. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Faults‐slip‐through—a concept for measuring the efficiency of the test process
Authors: Damm Lars‐Ola , Lundberg Lars , Wohlin Claes
Published: March 2006

In market‐driven development where time‐to‐market is of crucial importance, software development companies seek improvements that can decrease the lead‐time and improve the delivery precision. One way to achieve this is by analyzing the test process since rework commonly accounts for more than half of the development time. A large reason for high rework costs is fault slippages from earlier phases where they are cheaper to find and remove. As an input to improvements, this article introduces a measure that can quantify this relationship. That is, a measure called faults‐slip‐through, which determines the faults that would have been more cost‐effective to find in an earlier phase. The method presented in this article also determines the excessive costs of the faults that slipped through phases, i.e. the improvement potential. The method was validated through practical application in two software development projects at the telecom company Ericsson AB. The results of the case study determined that the implementation phase had the largest improvement potential in the two studied projects since it caused a large faults‐slip‐through to later phases, i.e. 85 and 86% of the total improvement potential of each project. Copyright © 2006 John Wiley & Sons, Ltd.
Future great structural engineering building design firms
Authors: Hart Gary C.
Published: March 2006

This paper presents the author's position on what the organizational structure should be for a great structural engineering building design firm. Copyright © 2005 John Wiley & Sons, Ltd.
Nonlinear analysis for performance‐based earthquake engineering
Authors: Moehle Jack P.
Published: March 2006

Earthquake engineering design of buildings increasingly is using nonlinear dynamic analysis procedures to demonstrate building performance. These procedures require: an understanding of the relation between performance and nonlinear modeling; selection and manipulation of ground motions appropriate to design hazard levels; selection of appropriate nonlinear models and analysis procedures; and interpretation of results to determine design quantities based on nonlinear dynamic analysis procedures. These topics are discussed with an emphasis on tall buildings. Copyright © 2005 John Wiley & Sons, Ltd.
The case for seismic superiority of well‐engineered tall buildings
Authors: Naeim Farzad , Graves Robert W.
Published: March 2006

The objective of this paper is to bring the lingering debate over whether more rigid or more flexible buildings fare better during major earthquakes to an end. Historical data, design experience, and ground motions obtained from simulation of a magnitude 7·1 blind fault rupture directly below downtown Los Angeles are utilized in this study. Assuming the same level of attention to design, detailing, and construction workmanship is applied to buildings of all heights resulting in well‐engineered buildings, the results indicate that well‐engineered tall buildings are substantially safer than shorter, stiffer, buildings when subjected to strong earthquake ground motions. This is true even in the case of strong ground motions containing significant directivity and near‐source velocity pulses. Copyright © 2005 John Wiley & Sons, Ltd.
Clinical gait and stepping performance measures in older adults
Authors: Alexander N. B. , Goldberg A.
Published: March 2006

Problems with ambulation and mobility are frequent problems in older adults. Each year, about one in 100 older adults develops new severe mobility disability. Assessment of abnormal gait constitutes a major component of clinical practice and may lead to fall reduction. Clinicians can benefit from simple gait and mobility assessment tools to be used in busy clinical settings. This review focuses on gait and stepping performance measures that can be used by the busy clinician to assess gait, mobility performance, balance, and falls risk in the older adult.
Disability and physical activity in late life—research models and approaches
Authors: Heikkinen E.
Published: March 2006

Prevention of disability in late life has become a major public health concern, a key area of ageing research, and also an important target for the development of effective interventions. The increase in life expectancy and the resulting growth of the elderly population are also thought to be driving up the number of elderly people with disabilities. Despite the message that regular moderate physical activity has substantial health benefits even in very old age, older people remain largely sedentary. The most popular theoretical model for researching the development of disability is the disablement process, which is widely used, in the gerontological literature. The main pathway according to this model leads from diseases and injuries to impairments, functional limitations, and disability. This approach has been challenged most particularly by models, which emphasize the social construction and determinants of disability. Numerous physical exercise interventions have aimed at preventing impairments, functional limitations and disability, and at promoting independent living in late life. A review of the results of these interventions shows that exercise can indeed be effective in preventing impairments and functional limitations, but the evidence regarding the prevention of disability and dependency is inconclusive. The inconsistency of the results is related to differences in research models and approaches, cultural and other differences between the populations studied, and variability in research designs and methods, including definitions of key variables. In the future, research-addressing disability in late life needs to focus on the dynamic interactions between individuals and their social, physical, and cultural environment. Furthermore, randomized trials that are larger and longer than most existing studies of physical activity need to be conducted. Additional evidence can also be obtained by well-conducted observational studies focusing on the prevention of progressive disability related to chronic conditions. One of the key areas of development is in improving the definition of both independent (physical activity and exercise) and outcome (functional limitations, disability) variables. A further challenge is presented by the investigation of dose–response relationships, including both beneficial and possible adverse effects of exercise.
N‐Acetylcysteine‐induced changes in susceptibility of transformed eukaryotic cells to bacterial invasion
Authors: Gamaley Irina , Efremova Tatiana , Kirpichnikova Ksenia , Kever Ludmila , Komissarchik Yan , Polozov Yuri , Khaitlina Sofia
Published: March 2006

The effect of N‐acetylcysteine (NAC) on morphological and physiological properties of “normal” 3T3 and 3T3‐SV40 fibroblasts was studied. Incubation of the cells with 10 and 20 mM NAC for 20 h resulted in a reversible increase in the intracellular level of reduced glutathione and disorganization of actin cytoskeleton. Surprisingly, upon removal of NAC, 3T3‐SV40 fibroblasts demonstrated formation of well‐adhered cells with structured 3T3‐like stress‐fibers. Neither changes in glutathione levels, nor cytoskeleton disorganization/assembly abolished resistance of 3T3 cells to invasion by the bacterium Escherichia coli A2. On the other hand, pretreatment with NAC converted bacteria‐susceptible 3T3‐SV40 cells into resistant ones. These results show that NAC can induce partial reversion of transformed phenotype. We suggest that this effect is due to NAC‐induced modifications of cell surface proteins rather than to changes in the level of intracellular glutathione.
Psychological stress and the severity of post‐inflammatory visceral hyperalgesia
Authors: Liebregts Tobias , Adam Birgit , Bertel Anton , Lackner Carolin , Neumann Jens , Talley Nicholas J. , Gerken Guido , Holtmann Gerald
Published: March 2006

Objectives: Lowered visceral sensory thresholds are a key finding in at least a subgroup of patients with functional bowel disorders. Stress and inflammation contribute to this altered visceral sensory function. We aimed to elucidate the role of repetitive stress and acute mucosal inflammation, alone and in combination, on sensory function.

Methods: In randomized order, trinitrobenzenesulfonic acid (TNBS) plus the equal amount of ethanol or saline were instilled into the colorectum of female Lewis rats. Colorectal distensions (CRD) were performed with a barostat device (3min/40mmHg); to quantify the visceromotor response (VMR) to CRD, electromyographic activity (EMG) of the abdominal muscles was recorded. In randomized order, equal numbers of both treatment groups underwent either seven days (1h/day) repetitive water avoidance stress (WAS) or sham WAS. CRD's were conducted 28 days later. Colonic tissue samples were obtained to characterize inflammation and blood samples were taken at day 28 to measure plasma IL‐2 levels by enzyme‐linked immunosorbent assay (ELISA).

Results: Compared to controls (662±114μV) TNBS (1081±227μV), WAS (1366±125μV) and the combination of both (1477±390μV) significantly augmented the VMR to CRD. TNBS and/or WAS caused significant inflammatory changes at day 5, while only TNBS+WAS also showed signs of mucosal inflammation on day 14 and significantly elevated IL‐2 levels on day 28.

Conclusions: Stress and inflammation cause long lasting alterations of visceral sensory function. Concomitant stress further increases post‐inflammatory visceral hyperalgesia.
Synergistic interactions between the dual serotonergic, noradrenergic reuptake inhibitor duloxetine and the non‐steroidal anti‐inflammatory drug ibuprofen in inflammatory pain in rodents
Authors: Jones Carrie K. , Peters Steven C. , Shannon Harlan E.
Published: March 2006

Objectives:The present study was undertaken to characterize whether the pharmacologic interaction between duloxetine, a balanced serotonergic and noradrenergic reuptake inhibitor, and the non‐steroidal anti‐inflammatory drug ibuprofen was simply additive, less than additive, or greater than additive (i.e., synergistic) in preclinical models of visceral and inflammatory pain, specifically acetic acid‐induced writhing in mice and carrageenan‐induced thermal hyperalgesia and mechanical allodynia in rats.

Methods:In the writhing test, male CF‐1 mice were injected intraperitoneally with 0.55% acetic acid and 5min later the number of writhes was counted over a 5‐min period. In the carrageenan models, male Sprague‐Dawley rats were injected with a 1.5% carrageenan solution into the ventral surface of the hind paw; hypersensitivity to thermal and mechanical stimuli was subsequently evaluated 2h post‐carrageenan.

Results:Vehicle or a dose of duloxetine alone (1–100mg/kg), ibuprofen alone (10–300mg/kg), or duloxetine and ibuprofen in combination in a dose‐ratio of 1:10 duloxetine:ibuprofen were orally administered 30 or 60min before testing. Isobolographic analysis of the effects of duloxetine in combination with ibuprofen revealed a significant synergistic (greater than additive) interaction between duloxetine and ibuprofen both for reducing acetic acid‐induced writhing and carrageenan‐induced thermal hyperalgesia, but were additive for reversing mechanical allodynia.

Conclusions:Our data indicate that duloxetine and ibuprofen have synergistic efficacy in a visceral and an inflammatory pain model in rodents, and suggest that duloxetine and ibuprofen in combination may provide a useful approach to the clinical treatment of persistent pain, particularly inflammation‐related pain.
Source monitoring deficits in hallucinating compared to non-hallucinating patients with schizophrenia
Authors: Brunelin Jerome , Combris Marion , Poulet Emmanuel , Kallel Lassad , D’Amato Thierry , Dalery Jean , Saoud Mohamed
Published: March 2006

In two source memory tests, hallucinating patients with schizophrenia (N = 30), compared to non-hallucinating (N = 31), are impaired in recognizing internal self-generated items and misattribute them to an external event. They are not impaired in recognizing events from two internal sources. Results support a selective source-monitoring deficit in the occurrence of auditory hallucinations.