bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arsenite inhibits p53 phosphorylation, DNA binding activity, and p53 target gene p21 expression in mouse epidermal JB6 cells,
Authors: Tang Faqing , Liu Guangming , He Zhiwei , Ma Wei‐Ya , Bode Ann M. , Dong Zigang 
Published: May 2006

AbstractEpidemiologic investigations demonstrated that arsenite exposure increases the risk of various human cancers, including skin, lung, bladder, and kidney cancers. However, oral administration of arsenite alone has failed to induce tumors in animal models, suggesting that arsenic may act to enhance mutagenicity induced by other carcinogens. Arsenite may function as a co‐carcinogen, acting by inhibiting repair of carcinogen‐induced DNA damage mediated by p53 and p21, a p53 target gene. To elucidate the interaction between arsenite and p53 tumor suppressor protein, we studied the effect of arsenite on ultraviolet B (UVB)‐induced p53 phosphorylation, p53 DNA binding activity, and p53‐induced target gene transactivation in the JB6 Cl41 mouse epidermal skin cell model. Our results indicated that arsenite suppressed UVB‐induced p53 phosphorylation and p53 DNA binding activity. Arsenite also inhibited casein kinase 2 (CK2) activity and decreased p53‐regulated p21 protein expression. These data suggest that the direct inhibition of p53 functional activation is one of the mechanisms through which arsenite interferes with p53 function, and thus may be a significant mechanism for the co‐carcinogenic effects of arsenite. © 2006 Wiley‐Liss, Inc.
Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma
Authors: Yuan R‐H , Jeng Y‐M , Chen H‐L , Lai P‐L , Pan H‐W , Hsieh F‐J , Lin C‐Y , Lee P‐H , Hsu H‐C 
Published: May 2006

AbstractStathmin, a major microtubule‐depolymerizing protein, is involved in cell cycle progression and cell motility. This study aimed to elucidate its role in the progression, early tumour recurrence (ETR), and prognosis of hepatocellular carcinoma (HCC). Stathmin mRNA was overexpressed in 88/156 (56%) resected, unifocal, primary HCCs, while p53 mutation was present in 72 (46%) and osteopontin mRNA overexpression in 79 (51%). Stathmin mRNA expression exhibited high concordance (93%) with protein expression in 107 cases examined by immunohistochemistry. Stathmin overexpression correlated with high α‐fetoprotein (>200 ng/ml, p = 0.02), larger tumour size (>5 cm, p = 0.012), high tumour grade (p < 0.0002), high tumour stage (stage IIIA–IV) with vascular invasion and various degrees of intrahepatic metastasis (p < 1 × 10−8), ETR (p = 0.003), and lower 5‐year survival (p = 0.0007). Stathmin protein expression was often more intense in the peripheral regions of tumour trabeculae, tumour borders, and portal vein tumour thrombi. Stathmin overexpression correlated with p53 mutation (p = 0.017) and osteopontin overexpression (p = 1 × 10−8), both of which were associated with vascular invasion (both p < 0.0001) and poorer prognosis (p < 0.0004 and p = 0.0004, respectively). Regardless of the status of p53 mutation or osteopontin expression, stathmin overexpression was associated with higher vascular invasion (all p < 0.0001). Approximately 90% of HCCs harbouring stathmin overexpression with concomitant p53 mutation or osteopontin overexpression exhibited vascular invasion, and hence the lowest 5‐year survival, p = 0.00018 and p = 0.0009, respectively. However, we did not find that stathmin overexpression exerted prognostic impact independent of tumour stage. In conclusion, stathmin expression correlates with metastatic potential, is an important prognostic factor for HCC, and may serve as a useful marker to predict ETR. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
GLP‐compliant assay validation studies: considerations for implementation of regulations and audit of studies
Authors: Li Henry , Sharp Garreth , Pilkington Connie , Pifat Dominique , Petteway Steve 
Published: May 2006

AbstractBioanalytical methods used in nonclinical safety studies are validated to demonstrate that the methods are reliable and reproducible for the intended use. Analytical method validation studies should be designed according to regulatory guidance on method validation. A cell‐based assay is described to discuss fundamental validation parameters, such as repeatability, immediate precision, accuracy, and linearity. A Good Laboratory Practice (GLP) compliance program provides a useful platform for ensuring data integrity in assay validation studies. A good understanding of the method validation concepts and regulatory requirements will help Quality Assurance Unit (QAU) auditors focus on key areas and be more effective when auditing assay validation protocols, final reports, and associated data. Copyright © 2006 John Wiley & Sons, Ltd.
International Marketing Applications according to the ICH CTD format: comparison of structure and document requirements
Authors: Gelman Rita Segal 
Published: May 2006

AbstractWith the development of the Common Technical Document (CTD) by the International Conference on Harmonisation (ICH), United States, European Union and Japan now have a common format for the organization of documents in regulatory applications. This paper presents a top‐level assessment of how the required technical contents of the Biologic License Application (BLA), the Marketing Authorization Application (MAA) and Japan's New Drug Application should be structured according to the ICH CTD format. The article may be of assistance for Quality Assurance auditor when auditing MAAs. Copyright © 2006 John Wiley & Sons, Ltd.
Receptor recycling mediates plasma membrane recovery of dopamine D1 receptors in dendrites and axons after agonist‐induced endocytosis in primary cultures of striatal neurons
Authors: Martin‐Negrier Marie‐Laure , Charron Giselle , Bloch Bertrand 
Published: May 2006

AbstractThe pharmacological stimulation of G‐protein‐coupled receptor induces receptor internalization. Receptor's fate after the step of internalization remains poorly characterized despite its incidence on the neuronal responsiveness. In this context, we studied the dopamine (DA) D1 receptor (D1R) trafficking in a model of striatal neuronal culture that endogenously express the D1R. We first characterized by immunohistochemistry the spatial distribution of the compartments involved in the endocytic pathways and then the D1R trafficking in dendrites and axons. In dendrites, immunohistochemical analysis showed that acute stimulation by the D1R agonist SKF 82958 (1 μM) induces an internalization of D1R in early endosomes labeled with Alexa‐488‐conjugated transferrin. We show that, 20 min after removal of the agonist, the D1R immunolabeling pattern returns to the basal state in dendrites and in axons. Recovery was unaffected by cycloheximide (70 μM) but was prevented by monensin (100 μM) that inhibits endosomal acidification and receptor recycling. These data suggest that dendritic and axonal D1Rs are internalized after agonist stimulation and targeted to the recycling pathway demonstrating that the machinery involved in GPCR endocytosis and recycling is functional both in dendrites and in axons. Temporal characteristics observed for the recovery of D1R density to the basal state and those observed for the resensitization process strongly suggest that D1R recycling supports the receptor resensitization. Synapse 60:194–204, 2006. © 2006 Wiley‐Liss, Inc.
The preparation of ZnGa2O4 doped with Mn‐Mg and Tm for green and blue phosphors
Authors: Singh Binod Kumar , Ryu Hojin , Kim Chang‐Hae , Jung Ha‐Kyun , Park Jung‐Kyu , Jung Kyeung‐Yeol , Chang Ho‐Jung 
Published: May 2006

AbstractPhosphor powders of zinc gallate (ZnGa2O4) with Mg and Mn for green and Tm‐Mg for blue luminescence were prepared by solid state reaction method for their improved luminescent properties. Green‐luminescence emitting ZnMnGa2O4 reached maximum intensity at Mn = 0.005 mol% and further improvement was achieved by the addition of Mg2+. Tm‐Mg based zinc gallate phosphor exhibited a strong blue emission, centered at ∼420 nm with the maximum intensity achieved for 0.003 mol% of Mg and 0.015 mol% of Tm. This study established the possibilities of controlling the luminescent characteristics of zinc gallate by adding various elements. © 2006 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
High performance control implementation of stand alone induction generator using active power filter
Authors: Nishida Katsumi , Ahmed Tarek , Nakaoka Mutsuo 
Published: May 2006

AbstractThis paper presents a novel dynamic model in the stationary reference frame for a diode bridge rectifier with a DC‐link filter directly connected to a three‐phase induction generator (IG). Moreover, a hybrid excitation system, consisting of a capacitor bank and a small‐scale active power filter (APF), regulates the stand‐alone IG system's output voltages by controlling its reactive‐current component, and cancels harmonic currents generated by a nonlinear diode rectifier load. A deadbeat current control strategy for the small‐scale APF is used to enhance the operating performances of the stand‐alone IG. This power generating system can be used for small hydro and wind rural applications where the generated electrical power is supplied to DC and AC loads. The measurement results validate the proposed power generating system, with the deadbeat current controller as a good application for the IG to reduce the total system cost and the required number of sensors. © 2006 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
An extra dimension in nucleic acid sequence recognition
Authors: Fox Keith R , Brown Tom 
Published: May 2006

Introduction 312Triple helices in DNA 312Chemically modified TFOs 313Further development 316Recognition of GC base pairs 316Recognition of TA base pairs 316Recognition of AT base pairs 317Recognition of CG base pairs 317RNA triplexes 317Kinetics of triplex formation 318Practical applications of triplexes 318Conclusions 319References 319Watson–Crick base pairing is a natural molecular recognition process that has been exploited in molecular biology and universally adopted in many fields. An additional mode of nucleic acid sequence recognition that could be used in combination with normal base pairing would add an exta dimension to nucleic acid interactions and open up many new applications. In principle the triplex approach could provide this if developed to recognize any DNA sequence. To this end modified nucleosides have been incorporated into triple-helix-forming oligonucleotides (TFOs) and used to recognize mixed sequence DNA with high selectivity and affinity at neutral pH. Continuing developments are directed towards improving TFO affinity at high pH and increasing triplex association kinetics. A number of applications of triplexes are currently being explored.
INHIBITION OF THE EFFECTS OF ANGIOTENSIN II ON ADRENAL STEROID PRODUCTION BY DIETARY SODIUM
Authors: Davis Warren W. , Burwell Lawrence R. , Bartter Frederic C. 
Published: May 2006

The pressor octapeptide, angiotensin II, can stimulate the production of aldosterone by the adrenal cortex. The present results show that in the dog a high-sodium diet can eliminate the steroidogenic action of angiotensin II, which is thus dissociated from the pressor action which remains.
Angiotensin II was infused intravenously for 48 hours into conscious, undisturbed hypophysectomized dogs that were receiving each day either 60 or 200 mEq of dietary sodium. Blood pressure and secretion of aldosterone, corticosterone, and cortisol were measured (1) throughout the infusion in some dogs, and (2) at the end of the infusion in all dogs. In those dogs receiving 60 mEq of sodium, angiotensin II elevated the blood pressure and produced sustained increases of secretion of aldosterone, corticosterone, and cortisol. In those dogs receiving 200 mEq of sodium, angiotensin II, while retaining its pressor activity, had no effect on the production of aldosterone, corticosterone, or cortisol after 24 hours. Thus, if angiotensin II can produce hypertension clinically, there need not be secondary aldosteronism as well.
ACETYLCHOLINE AND ITS THIOLESTER AND SELENOLESTER ANALOGS: CONFORMATION, ELECTRON DISTRIBUTION, AND BIOLOGICAL ACTIVITY
Authors: Shefter Eli , Mautner Henry G. 
Published: May 2006

The crystal structures of acetylthiolcholine bromide and propionylthiolcholine iodide were elucidated. Acetylthiolcholine was found to be essentially isosteric with acetylselenolcholine, while the conformation of these compounds was quite different from that of acetylcholine.
The importance of conformation and electron distribution in the biological actions of choline esters is discussed.
EQUILIBRIUM MEASUREMENTS OF EMBRYONIC CHICK CELL ADHESIVENESS, I. SHAPE EQUILIBRIUM IN CENTRIFUGAL FIELDS
Authors: Phillips Herbert M. , Steinberg Malcolm S. 
Published: May 2006

Sorting-out and other morphogenetic rearrangements of embryonic cells have been attributed to the spontaneous movements of mutually adhesive cells toward configurations of minimal adhesive free energy. Testing this hypothesis requires measuring those particular adhesive properties that would determine such equilibrium configurations.
We have devised a modification of the sessile drop method for making the required measurements.
This communication is a preliminary report of experiments demonstrating that intercellular adhesiveness is reflected in the equilibrium shapes of centrifuged cell aggregates.
G (Gross) and H-2 Cell-Surface Antigens: Location on Gross Leukemia Cells by Electron Microscopy with Visually Labeled Antibody
Authors: Aoki Tadao , Boyse Edward A. , Old Lloyd J. , de Harven Etienne , Hämmerling Ulrich , Wood Harry A. 
Published: May 2006

The hybrid-antibody method of locating cell-surface antigens in electron micrographs, with either ferritin or southern bean mosaic virus as the visual marker, was applied to the cells of a transplanted murine leukemia induced by Gross virus. The two antigens studied were (
a
) G (Gross) cell-surface antigen, which is a specific component of cells infected with Gross virus and is identified by cytotoxic hyperimmune C57BL/6 antiserum, and (
b
) H-2 antigen, which is the major histocompatibility determinant of the mouse.

Both antigens were represented on the cell surface in discrete circumscribed areas. Neither antigen was present on free Gross virions or on virions in the process of budding from the cell surface.
Thus G cell-surface antigen identified by C57BL mouse cytotoxic antiserum is not a constituent of the viral envelope, which accounts for the poor virus-neutralizing capacity of such antibody.

Virus maturation may take place preferentially at regions of the cell surface where H-2 and G antigens are absent, for budding was seldom seen in H-2
+
sectors and never convincingly in G
+
sectors.

In other experiments, serum from an untreated NZB mice aged 16 months gave labeling of the virion only, showing that this mouse strain, in contrast to C57BL and other strains, forms antibody to envelope antigen of Gross virus.
Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency: Activity in Normal, Mutant, and Heterozygote-Cultured Human Skin Fibroblasts
Authors: Fujimoto Wilfred Y. , Seegmiller J. Edwin 
Published: May 2006

Cultured skin fibroblasts from patients deficient for the enzyme hypoxanthine-guanine phosphoribosyltransferase (PRT) activity show very low but nevertheless significant levels of apparent PRT enzyme despite absence of detectable activity (<0.004% of normal) in erythrocytes of the same patients. In fibroblasts this mutant enzyme is more heat labile than the normal enzyme. These findings indicate that PRT deficiency in this disorder is not due to a deletion mutation of the PRT locus.
Individual cultured skin fibroblasts from heterozygote females for PRT deficiency show normal, intermediate, or very low levels of PRT activity. The mosaicism demonstrated in the heterozygotes for this X-linked disorder accounts for the cells with normal and very low activities of PRT. Intermediate activity can best be explained by the phenomenon of metabolic cooperation presumably from the transfer of either PRT enzyme or messenger RNA, from normal to mutant cells.
Reaction Sites of Rotenone, Piericidin A, and Amytal in Relation to the Nonheme Iron Components of NADH Dehydrogenase
Authors: Gutman M. , Singer Thomas P. , Beinert Helmut , Casida John E. 
Published: May 2006

The locus of inhibition of nicotinamide adenine dinucleotide, reduced form (NADH) oxidation in mitochondria by rotenone, piercidin A, and barbiturates is considered in the light of available information. Most lines of evidence indicate that the point of inhibition is on the O
2
side of NADH dehydrogenase. Kinetic experiments on the substrate-induced appearance of the electron paramagnetic resonance signal at
g
= 1.94 in membrane preparations (ETP) reveal that these inhibitors do not interfere with the reduction of the electron paramagnetic resonance detectable iron by NADH. Our spectrophotometric studies on complex I give no evidence for absorbance differences between untreated and rotenone or piericidin inhibited preparations, which can be attributed to nonheme iron. Whatever changes were observed appear to be due to cytochromes. These experiments, therefore, do not support the idea that in inhibited preparations electron transport is interrupted between the flavin and nonheme iron components of NADH dehydrogenase.

The specific binding of rotenone and piericidin seems to involve both lipid and protein. The possibility that NADH dehydrogenase participates in the binding is suggested by the apparent stoichiometric relation between specific binding site titer and NADH dehydrogenase content and the profound effect of mersalyl inhibition of the enzyme on piericidin binding capacity.
ETP, electron transport particle.
Formation of a Vaccinia Virus Structural Polypeptide from a Higher Molecular Weight Precursor: Inhibition by Rifampicin
Authors: Katz Ehud , Moss Bernard 
Published: May 2006

A vaccinia virus core polypeptide, with a molecular weight of 76,000 and a relative deficiency in tryptophan, was shown by pulse-chase experiments to form from a precursor. The latter may be a rapidly labeled, 125,000-molecular weight, tryptophan-deficient, virus-induced polypeptide, which diminished in quantity during the chase period and was barely detectable after two to three hours.
Rifampicin completely prevented the formation of the core polypeptide without inhibiting the synthesis of the precursor. A rifampicin-resistant vaccinia mutant was used to demonstrate the specificity of this effect. The sequence of events after the removal of the drug suggested that cleavage of the precursor occurs during the formation of the virus core. Rifampicin appears to act by interrupting earlier maturational events which precede the formation of the core polypeptide.
The Rolling Circle for ϕX DNA Replication, II. Synthesis of Single-Stranded Circles
Authors: Dressler David 
Published: May 2006

ϕX-infected cells have been allowed to incorporate tritiated thymidine late in the phage life cycle when single-stranded circles are the product of DNA synthesis. Virtually all of the radioactivity is recovered in a continuum of actively replicating viral DNA molecules. These molecules are termed rolling circle intermediates because they are characterized by three structural properties. They possess positive strands that are longer than the length of a mature viral genome, and negative strands that are covalently closed single-stranded circles. The 3′ termini of the long positive strands lie upon the template rings, while the 5′ ends are free in solution.
From these experimental data, the basic mode of synthesis is deduced to involve the continuous elongation of the open positive strand by endless copying around the circular negative strand template. As new bases are added to the template-bound (3′) end of the positive strand, the distal (5′) end is displaced from the template ring as a single-stranded tail of increasing length. It is the tail which serves as the source of material for progeny chromosomes.
These data confirm our characterization of this ϕX intermediate, which initially was based only on the possession of long positive strands, and extend this characterization to include experimental statements about the circular nature of the template DNA strand, and the 5′ to 3′ direction of polynucleotide chain growth within the intermediate. Moreover, the description can now be applied to all of the molecules which acquire label during a pulse.
Ribosome Formation is Blocked by Camptothecin, a Reversible Inhibitor of RNA Synthesis
Authors: Wu Roy S. , Kumar Ajit , Warner Jonathan R. 
Published: May 2006

A new drug, camptothecin, has been used to study the regulation of ribosome synthesis in HeLa cells. 5 μM camptothecin inhibits the synthesis of heterogeneously sedimenting nuclear RNA by about 70%. Camptothecin also blocks a specific step in the processing of ribosomal precursor RNA, allowing the conversion of 45S RNA to 32S RNA, but inhibiting the conversion of 32S RNA to 28S RNA. The action of camptothecin, unlike that of actinomycin D, is rapidly reversible. Within 5 min after the removal of the drug, ribosomal precursor RNA synthesis and maturation resume at the normal rate.
Ribosomal proteins made in the presence of camptothecin do not accumulate in the nucleolus, and are not subsequently used to form ribosomes if RNA synthesis is allowed to resume.
Absence of Adaptive Modification in Developing Retinotectal Connections in Frogs after Visual Deprivation or Disparate Stimulation of the Eyes
Authors: Jacobson Marcus 
Published: May 2006

Action potentials evoked in the tectum by visual stimulation of the ipsilateral eye were absent in frog larvae and developed during metamorphosis. Formation of the connections underlying these responses is not based on the animal's visual experience. The development of the ipsilateral retinotectal projection occurred normally in frogs reared through metamorphosis in the dark from midlarval stages to adults. Inversion of one eye of frog larvae did not affect the development of ipsilateral retinotectal projections, which developed according to the inherent correspondences between the retinae regardless of the disparities produced by changing the relative positions of the eyes. No compensatory changes occurred in the retinotectal projections in response to the surgical derangement.
Skin grafts completely occluding one eye, which were made at early larval stages and left in place for up to 88 days, did not affect the development of normal ipsilateral retinotectal connections. However, abnormal ipsilateral tectal responses evoked by stimulation through either the normal eye or the occluded eye were found in adult frogs after occlusion of one eye from larval stages for more than 121 days. It was concluded that visual stimulation is not required for the normal development of ipsilateral retinotectal connections but is required for their long-term maintenance.