bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Zn⋅⋅⋅Zn Separation on the Hydrolytic Activity of Model Dizinc Phosphodiesterases
Authors: Bauer‐Siebenlist Bernhard , Meyer Franc , Farkas Etelka , Vidovic Denis , Dechert Sebastian 
Published: May 2005

AbstractFrom the study of highly preorganized model systems, experimental support has been obtained for a possible functional role of the Zn–(H)O⋅⋅⋅HO(H)–Zn motif in oligozinc hydrolases. The mechanistic relevance of such an array, which may be described as a hydrated form of a pseudo‐terminal Zn‐bound hydroxide, has recently been supported by DFT calculations on various metallohydrolase active sites. In the present targeted approach, the Zn⋅⋅⋅Zn distance in two related dizinc complexes has been controlled through the use of multifunctional pyrazolate‐based ligand scaffolds, giving either a tightly bridged Zn–O(H)–Zn or a more loosely bridged Zn–(H)O⋅⋅⋅HO(H)–Zn species in the solid state. Zn‐bound water has been found to exhibit comparable acidity irrespective of whether the resulting hydroxide is supported by strong hydrogen‐bonding in the O2H3 moiety or is in a bridging position between two zinc ions, indicating that water does not necessarily have to adopt a bridging position in order for its pKa to be sufficiently lowered so as to provide a Zn‐bound hydroxide at physiological pH. Comparative reactivity studies on the cleavage of bis(4‐nitrophenyl)phosphate (BNPP) mediated by the two dizinc complexes have revealed that the system with the larger Zn⋅⋅⋅Zn separation is hydrolytically more potent, both in the hydrolysis and the transesterification of BNPP. The extent of active site inhibition by the reaction products has also been found to be governed by the Zn⋅⋅⋅Zn distance, since phosphate diester coordination in a bridging mode within the clamp of two zinc ions is only favored for Zn⋅⋅⋅Zn distances well above 4 Å. Different binding affinities are rationalized in terms of the structural characteristics of the product‐inhibited complexes for the two different ligand scaffolds, with dimethyl phosphate found as a bridging ligand within the bimetallic pocket.
Structurally Diverse Second‐Generation [2.2]Paracyclophane Ketimines with Planar and Central Chirality: Syntheses, Structural Determination, and Evaluation for Asymmetric Catalysis
Authors: Lauterwasser Frank , Nieger Martin , Mansikkamäki Heidi , Nättinen Kalle , Bräse Stefan 
Published: May 2005

AbstractA set of 20 novel [2.2]paracyclophane ketimines with planar and central chirality has been synthesized from enantiomerically pure and racemic 5‐acyl‐4‐hydroxy[2.2]paracyclophane and α‐branched chiral amines. Their X‐ray structures were determined to elucidate the three‐dimensional structures and the absolute configuration. The ketimines were used as catalysts in the asymmetric 1,2‐addition reactions of diethylzinc with substituted benzaldehydes to furnish chiral alcohols in up to 95 % ee.
Radiotherapy alone or combined with surgery for salivary gland carcinoma
Authors: Mendenhall William M. , Morris Christopher G. , Amdur Robert J. , Werning John W. , Villaret Douglas B. 
Published: May 2005

AbstractBACKGROUNDThe authors analyzed the outcomes of patients treated with radiotherapy (RT) alone or combined with surgery for carcinoma of the salivary glands.METHODSBetween October 1964 and June 2003, 224 previously untreated patients were treated with curative intent with RT alone (n= 64) or combined with surgery (n= 160) at the University of Florida College of Medicine (Gainesville, FL). The median follow‐up period was 5.0 years (range, 0.4–31.6 years).RESULTSThe 10‐year local control rate was 75%. Multivariate analysis of local control revealed that T classification (P< 0.0001) and treatment group (P< 0.0001) impacted this end point. Patients treated with surgery and adjuvant RT had improved local control compared with patients treated with RT alone. The 10‐year locoregional control rate was 68%. Multivariate analysis of locoregional control revealed that overall stage (P< 0.0001) and treatment group (P= 0.0002) significantly influenced this end point. The 10‐year distant metastasis‐free survival rate was 68%. Multivariate analysis of distant metastasis‐free survival revealed that overall stage (P< 0.0001) significantly influenced this end point. The 10‐year cause‐specific and overall survival rates were 57% and 44%, respectively. Multivariate analysis of cause‐specific survival revealed that overall stage (P< 0.0001) significantly impacted this end point. Twenty‐three patients (10%) experienced severe complications.CONCLUSIONSA substantial proportion of patients with salivary gland carcinoma were cured with surgery combined with adjuvant RT. RT alone was used for patients with unresectable tumors and cured approximately 20% of those with advanced‐stage disease. The probability of cure was influenced by the extent of disease and treatment group. Cancer 2005. © 2005 American Cancer Society.
Recurrent central neurocytomas
Authors: Bertalanffy Alexander , Roessler Karl , Koperek Oskar , Gelpi Ellen , Prayer Daniela , Knosp Engelbert 
Published: May 2005

AbstractBACKGROUNDSince the first description of Central neurocytomas (CNs) as a benign tumor entity in 1982, there has been great enthusiasm regarding the benign course and the curative surgical approach to this disease. The current study was performed to investigate the frequency of disease recurrence during long‐term follow‐up.METHODSA retrospective analysis of the medical files with emphasis on clinicoradiologic findings and histologic and immunohistochemical features was performed.RESULTSBetween 1985–2003. surgical resection was performed in 14 patients with CNs ages 16–43 years (7 were female and 7 were male). Two patients (14%) died postoperatively and one patient had a malignant disease course (7%). In the remaining 11 patients, one patient with an incompletely resected CN had disease progression after 37 months but at the time of last follow‐up had had stable disease for 10 years. In addition, the authors reported 5 patients with disease recurrence occurring at a median of 67 months after surgery (range, 51–79 months after surgery), all of which occurred after complete surgical resection was performed. The observation period for the remaining 5 patients was short (median of 34 months [range, 5–44 months]). Extensive histologic and immunohistochemical workup did not identify any significant prognostic parameters. The MIB‐1 proliferation index ranged from 0.8–11% (median of 4.6%), but was reported to be 46.8% in the malignant transformed tumor. All patients with disease recurrence responded well to different forms of focal radiation therapy (gamma knife radiosurgery in three patients and interstitial irradiation in one patient) and for one patient with a recently detected recurrence, gamma knife radiosurgery was planned.CONCLUSIONSCNs appear to have a higher tendency to recur during long‐term follow‐up than previously reported, even after complete resection. Therefore, periodic neuroradiologic follow‐up examinations should be considered mandatory in all patients, even after several years. Cancer 2005. © 2005 American Cancer Society.
DNA damage in leukocytes of workers occupationally exposed to arsenic in copper smelters
Authors: Palus Jadwiga , Lewinska Dobroslawa , Dziubaltowska Elzbieta , Stepnik Maciej , Beck Jens , Rydzynski Konrad , Nilsson Robert 
Published: May 2005

AbstractInorganic arsenic (i‐As) is a known human carcinogen; however, humans continue to be exposed to i‐As in drinking water and in certain occupational settings. In this study, we used the Comet assay to evaluate DNA damage in the somatic cells of workers from three Polish copper smelters who were occupationally exposed to i‐As. Blood samples were collected from 72 male workers and 83 unexposed male controls and used for the detection of DNA damage, oxidative DNA damage, and DNA damage after a 3‐hr incubation in culture. Urine samples were collected to assess the level of exposure. The mean concentration of arsenic metabolites in urine [the sum of arsenite (AsIII), arsenate (AsV), monomethylarsenate (MMA) and dimethylarsenate (DMA)] and the concentrations of DMA (the main metabolite in urine) were higher in workers than in controls, but the differences were not statistically significant. By contrast, the level of DNA damage, expressed as the median tail moment, was significantly higher in the leukocytes of workers than in the controls. Comet assays conducted with formamidopyrimidine glycosylase (FPG) digestion to detect oxidative DNA damage indicated that oxidative lesions were present in leukocytes from both the exposed and control groups, but the levels of damage were significantly higher among the workers. Incubation of the cells in culture resulted in a significant reduction in the levels of DNA damage, especially among leukocytes from the workers, suggesting that the DNA damage was subject to repair. Our findings indicate that copper smelter workers have increased levels of DNA damage in somatic cells, suggesting a potential health risk for the workers. Although i‐As was present in air samples from the smelters and in urine samples from workers, no clear association could be made between i‐As exposure and the DNA damage. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.
Genotoxicity of drinking water disinfectants in plant bioassays
Authors: Monarca Silvano , Feretti Donatella , Zani Claudia , Rizzoni Marco , Casarella Silvia , Gustavino Bianca 
Published: May 2005

AbstractThe genotoxicity of two widely used drinking water disinfectants, sodium hypochlorite (NaClO) and chlorine dioxide (ClO2), and a new disinfectant, peracetic acid (PAA, CH3‐CO‐COOH), was evaluated in three short‐term plant tests: (1) induction of anaphase chromosome aberrations in the root cells of Allium cepa, (2) micronucleus induction in the root cells of Vicia faba, and (3) micronucleus induction in Tradescantia pollen cells. The study was carried out in the laboratory by directly exposing the plants to several concentrations of the disinfectants in redistilled water at unadjusted (acid) and adjusted (neutral) pHs. Both 0.1 and 0.2 mg/l NaClO induced chromosome aberrations in the Allium cepa test at acid pH, but concentrations up to 0.5 mg/l of all the disinfectants were negative at neutral pH. Concentrations ranging from 0.1 to 0.5 mg/l NaClO, ClO2, and PAA induced micronuclei in Vicia faba at acid pH, while 1–2 mg/l NaClO and ClO2 and 0.5–2 mg/l PAA gave positive responses at neutral pH. Most of concentrations of ClO2 produced positive responses in the Tradescantia micronucleus test. In general, the highest levels of genotoxicity were observed under acid conditions; at acid pH, significant effects were induced by low concentrations of ClO2 and PAA. Since the test concentrations of disinfectants are typical of those encountered in the biocidal treatment of tap water and similar concentrations are consumed daily by a large number of people, the genotoxicity of these compounds may constitute a significant public health concern. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.
A weighted cohort approach for analysing factors modifying disease risks in carriers of high‐risk susceptibility genes
Authors: Antoniou Antonis C. , Goldgar David E. , Andrieu Nadine , Chang‐Claude Jenny , Brohet Richard , Rookus Matti A. , Easton Douglas F. 
Published: May 2005

AbstractThe authors propose a novel approach to evaluate the effects of risk factors on disease risks in carriers of high‐penetrance alleles in disease susceptibility genes. Most studies to date have utilised data collected on carriers identified through ongoing genetic testing programs. The advantage of this approach is that it allows relatively large numbers of affected and unaffected carriers to be identified rapidly. However, genetic testing is targeted at individuals with a strong family history of disease, so that the selection of carriers is not random with respect to disease status. Risk factors are often analysed by standard cohort analysis methods, but these can be biased in retrospective studies if subjects are selected on the basis of phenotype. To overcome this problem, a weighted cohort approach is proposed, under which individuals are weighted according to certain sampling probabilities in order to mimic a true cohort. The method is illustrated by analyses of data from the International BRCA1/2 Carrier Cohort Study (IBCCS). Simulations demonstrate that the method gives rate ratio estimates that are close to unbiased provided that the absolute disease risks are well estimated. The power to detect associations is, however, reduced compared with an unweighted approach. Genet. Epidemiol. © 2005 Wiley‐Liss, Inc.
A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI‐cycle) to psychiatric disorders—focus on magnetic resonance spectroscopy (MRS) studies
Authors: Kim Hyeonjin , McGrath Brent M. , Silverstone Peter H. 
Published: May 2005

AbstractMyo‐inositol is an important part of the phosphatidylinositol second messenger system (PI‐cycle). Abnormalities in nerve cell myo‐inositol levels and/or PI‐cycle regulation has been suggested as being involved in the pathophysiology and/or treatment of many psychiatric disorders including bipolar disorder, major depressive disorder, panic disorder, obsessive‐compulsive disorder, eating disorders and schizophrenia. This review examines the metabolism and biochemical importance of myo‐inositol and the PI‐cycle. It relates this to the current in vivo evidence for myo‐inositol and PI‐cycle involvement in these psychiatric disorders, particularly focusing upon the magnetic resonance spectroscopy (MRS) findings in patient studies to date. From this review it is concluded that while the evidence suggests probable relevance to the pathophysiology and/or treatment of bipolar disorder, there is much less support for a significant role for the PI‐cycle or myo‐inositol in any other psychiatric disorder. More definitive investigation is required before PI‐cycle dysfunction can be considered specific to bipolar disorder. Copyright © 2005 John Wiley & Sons, Ltd.
Role of smoking in global and regional cancer epidemiology: Current patterns and data needs
Authors: Ezzati Majid , Henley S. Jane , Lopez Alan D. , Thun Michael J. 
Published: May 2005

AbstractAlthough smoking is widely recognized as a major cause of cancer, there is little information on how it contributes to the global and regional burden of cancers in combination with other risk factors that affect background cancer mortality patterns. We used data from the American Cancer Society's Cancer Prevention Study II (CPS‐II) and the WHO and IARC cancer mortality databases to estimate deaths from 8 clusters of site‐specific cancers caused by smoking, for 14 epidemiologic subregions of the world, by age and sex. We used lung cancer mortality as an indirect marker for accumulated smoking hazard. CPS‐II hazards were adjusted for important covariates. In the year 2000, an estimated 1.42 (95% CI 1.27–1.57) million cancer deaths in the world, 21% of total global cancer deaths, were caused by smoking. Of these, 1.18 million deaths were among men and 0.24 million among women; 625,000 (95% CI 485,000–749,000) smoking‐caused cancer deaths occurred in the developing world and 794,000 (95% CI 749,000–840,000) in industrialized regions. Lung cancer accounted for 60% of smoking‐attributable cancer mortality, followed by cancers of the upper aerodigestive tract (20%). Based on available data, more than one in every 5 cancer deaths in the world in the year 2000 were caused by smoking, making it possibly the single largest preventable cause of cancer mortality. There was significant variability across regions in the role of smoking as a cause of the different site‐specific cancers. This variability illustrates the importance of coupling research and surveillance of smoking with that for other risk factors for more effective cancer prevention. © 2005 Wiley‐Liss, Inc.
Overexpression of regucalcin suppresses cell death and apoptosis in cloned rat hepatoma H4‐II‐E cells induced by insulin or insulin‐like growth factor‐I
Authors: Fukaya Yuko , Yamaguchi Masayoshi 
Published: May 2005

AbstractThe role of regucalcin, a regulatory protein in intracellular signaling pathway, in cell death was investigated by using the cloned rat hepatoma H4‐II‐E cells overexpressing regucalcin. The hepatoma cells (wild‐type) and stable regucalcin/pCXN2 transfectants were cultured for 72 h in a medium containing 10% fetal bovine serum (FBS) to obtain subconfluent monolayers. After culture for 72 h, cells were further cultured for 24–72 h in a medium containing either vehicle, insulin (10−8 or 10−7M) or insulin‐like growth factor‐I (IGF‐I; 10−9 or 10−8M) in the absence of FBS. The number of wild‐type cells was significantly decreased by culture for 24, 48, or 72 h in the presence of insulin (10−8 or 10−7M) or IGF‐I (10−9 or 10−8M). Agarose gel electrophoresis showed the presence of low‐molecular‐weight deoxyribonucleic acid (DNA) fragments of adherent wild‐type cells cultured with insulin or IGF‐I. The effect of insulin or IGF‐I in stimulating cell death and DNA fragmentation in hepatoma cells (wild‐type) was significantly prevented in transfectants overexpressing regucalcin. Meanwhile, epinephrine (10−6 or 10−5M) or transforming growth factor‐β1 (10−13 or 10−12M) did not cause cell death of hepatoma cells. Insulin‐induced decrease in the number of wild‐type cells was significantly prevented by culture with caspase‐3 inhibitor (10−8M), although the effect of IGF‐I was not inhibited. The effect of insulin or IGF‐I in inducing the death of hepatoma cells (wild‐type) was significantly prevented in the presence of N ω‐nitro‐l‐arginine methylester (NAME), an inhibitor of nitric oxide synthase. Genistein (10−6M), an inhibitor of protein tyrosine kinase, or vanadate (10−5M), an inhibitor of protein tyrosine phosphatase, caused a significant decrease in the number of hepatoma cells (wild‐type). The effect of insulin in inducing the death of wild‐type cells was not seen in the presence of genistein or vanadate. The effect of IGF‐I on the death of wild‐type cells was observed in the presence of genistein or vanadate. The effect of genistein on cell death was significantly prevented in transfectants. Such effect was not seen with vanadate. This study demonstrates that insulin or IGF‐I stimulates cell death and apoptosis in the hepatoma cells, and that overexpression of regucalcin has a suppressive effect on cell death induced by insulin or IGF‐I that is mediated through different signaling pathway. © 2005 Wiley‐Liss, Inc.
MDA‐7/IL‐24 regulates proliferation, invasion and tumor cell radiosensitivity: A new cancer therapy?
Authors: Dent Paul , Yacoub Adly , Grant Steven , Curiel David T. , Fisher Paul B. 
Published: May 2005

AbstractThe novel cytokine MDA‐7/IL‐24 was identified by subtractive hybridization in the mid‐1990s as a cytokine whose expression increased during the induction of terminal differentiation, and that was either not expressed or was present at low levels in tumor cells compared to non‐transformed cells. Multiple studies from several laboratories have subsequently demonstrated that expression of IL‐24 in tumor cells, but not in non‐transformed cells, causes their growth arrest and ultimately cell death. In addition, IL‐24 has been noted to be a radiosensitizing cytokine, which in part is due to the generation of reactive oxygen species (ROS) and causing endoplasmic reticulum stress. Recent publications of Phase I trial data have shown that a recombinant adenovirus to express MDA‐7/IL‐24 (Ad.mda‐7 (INGN 241)) was safe and had tumoricidal effects in patients, which argues that IL‐24 may have therapeutic value. This review describes what is known about the impact of IL‐24 on tumor cell biology in addition to approaches that may enhance the toxicity of this novel cytokine. © 2005 Wiley‐Liss, Inc.
All‐electron density functional calculation on insulin with quasi‐canonical localized orbitals
Authors: Inaba Toru , Tahara Saisei , Nisikawa Nobutaka , Kashiwagi Hiroshi , Sato Fumitoshi 
Published: May 2005

AbstractAn all‐electron density functional (DF) calculation on insulin was performed by the Gaussian‐based DF program, ProteinDF. Quasi‐canonical localized orbitals (QCLOs) were used to improve the initial guess for the self‐consistent field (SCF) calculation. All calculations were carried out by parallel computing on eight processors of an Itanium2 cluster (SGI Altix3700) with a theoretical peak performance of 41.6 GFlops. It took 35 h for the whole calculation. Insulin is a protein hormone consisting of two peptide chains linked by three disulfide bonds. The numbers of residues, atoms, electrons, orbitals, and auxiliary functions are 51, 790, 3078, 4439, and 8060, respectively. An all‐electron DF calculation on insulin was successfully carried out, starting from connected QCLOs. Regardless of a large molecule with complicated topology, the differences in the total energy and the Mulliken atomic charge between initial and converged wavefunctions were very small. The calculation proceeded smoothly without any trial and error, suggesting that this is a promising method to obtain SCF convergence on large molecules such as proteins. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 987–993, 2005
Erythroid cell differentiation is characterized by nuclear matrix localization and phosphorylation of protein kinases C (PKC) α, δ, and ζ
Authors: Marchisio Marco , Santavenere Eugenio , Paludi Maya , Gaspari Anna Rita , Lanuti Paola , Bascelli Adriana , Ercolino Eva , Di Baldassarre Angela , Miscia Sebastiano 
Published: May 2005

AbstractProtein kinases C (PKC) ζ expression and phosphoryation at nuclear level during dimethyl sulfoxide (DMSO)‐induced differentiation in Friend erythroleukemia cells have been previously reported, suggesting a possible role of this PKC isoform in the DMSO‐related signaling. In order to shed more light on this tantalizing topic, we investigated PKC intracellular and sub‐cellular localization and activity during DMSO‐induced erythroid differentiation. Results indicated that at least PKC α, ζ, and δ are strongly and temporally involved in the DMSO‐induced differentiation signals since their expression and phosphorylation, though at different extents, were observed during treatments. Intriguingly, while PKC α and ζ associate to the nuclear matrix during the differentiation event, PKC δ appears to be residentially associated to the nuclear matrix. Furthermore, an evident downregulation of the β‐globin gene transcription (differentiation hallmark) was detected upon a progressive inhibition of these PKC isoforms by means of specific inhibitors, indicating, therefore, that PKC α, ζ, and δ phosphorylation play a crucial role in the control of erythroid differentiation. © 2005 Wiley‐Liss, Inc.