bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro/in Vivo scaling of alprazolam metabolism by CYP3A4 and CYP3A5 in humans
Authors: Hirota Noriko , Ito Kiyomi , Iwatsubo Takafumi , Green Carol E. , Tyson Charles A. , Shimada Noriaki , Suzuki Hiroshi , Sugiyama Yuichi 
Published: August 2002

AbstractWe attempted to predict the in vivo metabolic clearance of alprazolam from in vitro metabolic studies using human liver microsomes and human CYP recombinants. Good correlations were observed between the intrinsic clearance (CLint) for 4‐hydroxylation and CYP3A4 content and between the CLint for α‐hydroxylation and CYP3A5 content in ten human liver microsomal samples. Using the recombinant CYP isoforms expressed in insect cells, the CLint for CYP3A4 was about 2‐fold higher than the CLint for CYP3A5 in the case of 4‐hydroxylation. However, the CLint for CYP3A5 was about 3‐fold higher than the CLint for CYP3A4 in the case of α‐hydroxylation. The metabolic rates for 4‐ and α‐hydroxylation increased as the added amount of cytochrome b5 increased, and their maximum values were 3‐ to 4‐fold higher than those without cytochrome b5. The values of CLint, in vivo predicted from in vitro studies using human liver microsomes and CYP3A4 and CYP3A5 recombinants were within 2.5 times of the observed value calculated from literature data. The average CLint value (sum of 4‐ and α‐hydroxylation) obtained using three human liver microsomal samples was 4‐fold higher than that obtained using three small intestinal microsomal samples from the same donors, indicating the minor contribution of intestinal metabolism to alprazolam disposition. The area under the plasma concentration‐time curve (AUC) of alprazolam is reported to increase following co‐administration of ketoconazole and the magnitude of the increase predicted from the in vitro Ki values and reported pharmacokinetic parameters of ketoconazole was 2.30–2.45, which is close to the value observed in vivo (3.19). A quantitative prediction of the AUC increase by cimetidine was also successful (1.73–1.79 vs 1.58–1.64), considering the active transport of cimetidine into the liver. In conclusion, we have succeeded in carrying out an in vitro/in vivo scaling of alprazolam metabolism using human liver microsomes and human CYP3A4 and CYP3A5 recombinants. Copyright © 2001 John Wiley & Sons, Ltd.
Electrorotation of axolotl embryos
Authors: Abou‐Ali Ghalia , Kaler Karan V.I.S. , Paul Reginald , Björklund Natalie K. , Gordon Richard 
Published: August 2002

AbstractThe frequency dependent dielectric properties of individual axolotl embryos (Ambystoma mexicanum) were investigated experimentally utilizing the technique of electrorotation. Individual axolotl embryos, immersed in low conductivity media, were subjected to a known frequency and fixed amplitude rotating AC electric field and the ensuing rotational motion of the embryo was monitored using a conventional optical microscope. None of the embryos in the pregastrulation or neurulation stages of development exhibited any rotational motion over the field frequency range (10 Hz–5 MHz). Over the same frequency range, the embryos in the gastrulation stage of development exhibited both co‐field and counterfield rotation over different ranges of the applied field frequency. Typically, the counterfield rotation exhibited a peak in the rotation spectrum at ∼ 1 KHz while the co‐field peak was located at ∼ 1–2 MHz. The rotational spectral data was analyzed using a multishelled spherical embryo model to determine the electrical character of embryos during the early development stages (Stages 5–16; i.e., 16 cell through open neural plate stages). Bioelectromagnetics 23:214–223, 2002. © 2002 Wiley‐Liss, Inc.
Partial‐body exposure of human volunteers to 2450 MHz pulsed or CW fields provokes similar thermoregulatory responses*
Authors: Adair Eleanor R. , Mylacraine Kevin S. , Cobb Brenda L. 
Published: August 2002

AbstractMany reports describe data showing that continuous wave (CW) and pulsed (PW) radiofrequency (RF) fields, at the same frequency and average power density (PD), yield similar response changes in the exposed organism. During whole‐body exposure of squirrel monkeys at 2450 MHz CW and PW fields, heat production and heat loss responses were nearly identical. To explore this question in humans, we exposed two different groups of volunteers to 2450 MHz CW (two females, five males) and PW (65 μs pulse width, 104 pps; three females, three males) RF fields. We measured thermophysiological responses of heat production and heat loss (esophageal and six skin temperatures, metabolic heat production, local skin blood flow, and local sweat rate) under a standardized protocol (30 min baseline, 45 min RF or sham exposure, 10 min baseline), conducted in three ambient temperatures (Ta = 24, 28, and 31°C). At each Ta, average PDs studied were 0, 27, and 35 mW/cm2 (Specific absorption rate (SAR) = 0, 5.94, and 7.7 W/kg). Mean data for each group showed minimal changes in core temperature and metabolic heat production for all test conditions and no reliable differences between CW and PW exposure. Local skin temperatures showed similar trends for CW and PW exposure that were PD‐dependent; only the skin temperature of the upper back (facing the antenna) showed a reliably greater increase (P = .005) during PW exposure than during CW exposure. Local sweat rate and skin blood flow were both Ta‐ and PD‐dependent and showed greater variability than other measures between CW and PW exposures; this variability was attributable primarily to the characteristics of the two subject groups. With one noted exception, no clear evidence for a differential response to CW and PW fields was found. Bioelectromagnetics 22:246–259, 2001. © 2001 Wiley‐Liss, Inc.
Influence of a stationary magnetic field on water relations in lettuce seeds. Part II: Experimental results
Authors: Reina Francisco Garcìa , Pascual Luis Arza , Fundora Ilvelisse Almanza 
Published: August 2002

AbstractAn experimental study on water absorption by lettuce seeds previously treated in a stationary magnetic field of 0–10 mT is presented. A significant increase in the rate with which the seeds absorb water is observed in the interval 0–10 mT of magnetic treatment. An increment in the total mass of absorbed water in this interval is also observed. These results are consistent with the reports on the increase of germination rate of the seeds, and the theoretical calculation of the variations induced by magnetic fields in the ionic currents across the cellular membrane. The fields originate in changes in the ionic concentration and thus in the osmotic pressure which regulates the entrance of water to the seeds. The good correlation between the theoretical approach and experimental results provides strong evidence that the magnetic field alters the water relations in seeds, and this effect may be the explanation of the reported alterations in germination rate of seeds by the magnetic field. Bioelectromagnetics 22:596–602, 2001. © 2001 Wiley‐Liss, Inc.
Can molecular mechanisms of biological processes be extracted from expression profiles? Case study: endothelial contribution to tumor‐induced angiogenesis
Authors: Novatchkova Maria , Eisenhaber Frank 
Published: August 2002

AbstractWhereas the genome contains all potential developmental programs, expression profiles permit the determination of genes that are actively transcribed under defined physiological conditions. In this article, the idea of extracting biological mechanisms from expression data is tested. Molecular processes of the endothelial contribution to angiogenesis are derived from recently published expression profiles. The analysis reveals the sensitivity limits of experimental detection of transcriptional changes and how sequence‐analytic techniques can help to identify the function of genes in question. We conclude that the transcripts (http://mendel.imp.univie.ac.at/SEQUENCES/TEMS/) found to be up‐regulated in angiogenesis are involved in extracellular matrix remodeling, cellular migration, adhesion, cell‐cell communication rather than in angiogenesis initiation or integrative control. Comparison with tissue‐specific patterns of EST occurrence shows that, indeed, the presumptive tumor‐specific endothelial markers are more generally expressed by cell types involved in migration and matrix remodeling processes. This exemplary study demonstrates how bioinformatics approaches can be helpful in deriving mechanistic information from diverse sources of experimental data. BioEssays 23:1159–1175, 2001. © 2001 John Wiley & Sons, Inc.
Shedding light on sheddases: role in growth and development
Authors: Kheradmand Farrah , Werb Zena 
Published: August 2002

AbstractThe extracellular domains of several integral membrane proteins are released from the cell surface by a group of enzymes known as “sheddases” through a process called “ectodomain shedding”. Because many transmembrane growth and differentiation factors, including members of the epidermal growth factor (EGF) family that play a crucial role in development, require ectodomain shedding for proper action in vivo, proteolysis is now viewed as a regulatory mechanism in the developing embryos. Two recent reports by Zhao et al. provide evidence for the role of cell surface proteolysis by an ADAM (a disintegrin and metalloprotease) in the development of murine lung.(1,2) Inhibition of tumor necrosis factor‐α converting enzyme (TACE, ADAM17) by the hydroxamic acid‐based metalloprotease inhibitor (TAPI), (1) or a targeted mutation in Zn2+‐binding domain of TACE, (2) disrupts two essential epithelial functions in lung development: branching morphogenesis and cytodifferentiation. Evidence for the role of ADAMs as sheddases in development and growth factor signaling is discussed. BioEssays 24:8–12, 2002. © 2002 John Wiley & Sons, Inc.
Presenilin mutations and calcium signaling defects in the nervous and immune systems
Authors: Mattson Mark P. , Chan Sic L. , Camandola Simonetta 
Published: August 2002

AbstractPresenilin‐1 (PS1) is thought to regulate cell differentiation and survival by modulating the Notch signaling pathway. Mutations in PS1 have been shown to cause early‐onset inherited forms of Alzheimer's disease (AD) by a gain‐of‐function mechanism that alters proteolytic processing of the amyloid precursor protein (APP) resulting in increased production of neurotoxic forms of amyloid β‐peptide. The present article considers a second pathogenic mode of action of PS1 mutations, a defect in cellular calcium signaling characterized by overfilling of endoplasmic reticulum (ER) calcium stores and altered capacitive calcium entry; this abnormality may impair synaptic plasticity and sensitize neurons to apoptosis and excitotoxicity. The calcium signaling defect has also been documented in lymphocytes, suggesting a contribution of immune dysfunction to the pathogenesis of AD. A better understanding of the calcium signaling defect resulting from PS1 mutations may lead to the development of novel preventative and therapeutic strategies for disorders of the nervous and immune systems. BioEssays 23:733–744, 2001. © 2001 John Wiley & Sons, Inc.
Imaging of light emission from the expression of luciferases in living cells and organisms: a review
Authors: Greer Lee F. , Szalay Aladar A. 
Published: August 2002

AbstractLuciferases are enzymes that emit light in the presence of oxygen and a substrate (luciferin) and which have been used for real‐time, low‐light imaging of gene expression in cell cultures, individual cells, whole organisms, and transgenic organisms. Such luciferin–luciferase systems include, among others, the bacterial lux genes of terrestrial Photorhabdus luminescens and marine Vibrio harveyi bacteria, as well as eukaryotic luciferase luc and ruc genes from firefly species (Photinus) and the sea panzy (Renilla reniformis), respectively. In various vectors and in fusion constructs with other gene products such as green fluorescence protein (GFP; from the jellyfish Aequorea), luciferases have served as reporters in a number of promoter search and targeted gene expression experiments over the last two decades. Luciferase imaging has also been used to trace bacterial and viral infection in vivo and to visualize the proliferation of tumour cells in animal models. Copyright © 2002 John Wiley & Sons, Ltd.
Raman and surface enhanced Raman spectroscopy of 2,2,5,5‐tetramethyl‐3‐pyrrolin‐1‐yloxy‐3‐carboxamide labeled proteins: Bovine serum albumin and cytochrome c
Authors: Cavalu S. , Cîntă‐Pînzaru S. , Leopold N. , Kiefer W. 
Published: August 2002

Abstract2,2,5,5‐Tetramethyl‐3‐pyrrolin‐1‐yloxy‐3‐carboxamide (tempyo) labeled bovine serum albumin and cytochrome c at different pH values were prepared and investigated using Raman–resonance Raman (RR) spectroscopy and surface enhanced Raman scattering (SERS) spectroscopy. The Raman spectra of tempyo labeled proteins in the pH 6.7–11 range were compared to those of the corresponding free species. The SERS spectra were interpreted in terms of the structural changes of the tempyo labeled proteins adsorbed on the silver colloidal surface. The tempyo spin label was found to be inactive in the Raman–RR and SERS spectra of the proteins. The α‐helix conformation was concluded to be more favorable as the SERS binding site of bovine serum albumin. In the cytochrome c the enhancement of the bands assigned to the porphyrin macrocycle stretching mode allowed the supposition of the N‐adsorption onto the colloidal surface. © 2001 John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 62: 341–348, 2001
7Li‐NMR and FTIR studies of lithium, potassium, rubidium, and cesium complexes with ionophore lasalocid in solution
Authors: Pankiewicz Radosław , Schroeder Grzegorz , Gierczyk Błażej , Wojciechowski Grzegorz , Brzezinski Bogumił , Bartl Franz , Zundel Georg 
Published: August 2002

AbstractLasalocid metal salts were combined with 1 : 1 lithium and 2:2 potassium, rubidium, and cesium to form complexes. The nature of the lasolocid salt complexes was studied in a solid and chloroform by FTIR spectroscopy in the middle and far IR regions. The process of the complexation of lithium was also studied by 7Li‐NMR. In chloroform a 1 : 1 complex of lasalocid and Li+ ions was formed. Continuous absorption was observed in the far FTIR spectrum of this complex. It indicated large Li+ polarizability, which was due to fast fluctuations of the Li+ ions in the multiminima potentials, in the monomeric structure. In the lasalocid salt with the other monovalent cations (K+, Rb+, Cs+) 2:2 complexes were formed in which the cations showed cation polarizability, which strongly depended on the mass and the radius of the cations. © 2001 John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 62: 173–182, 2001
Expression of recombinant human acetylcholinesterase in transgenic tomato plants
Authors: Mor Tsafrir S. , Sternfeld Meira , Soreq Hermona , Arntzen Charles J. , Mason Hugh S. 
Published: August 2002

AbstractEnzyme therapy for the prevention and treatment of organophosphate poisoning depends on the availability of large amounts of cholinesterases. Transgenic plants are being evaluated for their efficiency and cost‐effectiveness as a system for the bioproduction of therapeutically valuable proteins. Here we report production of a recombinant isoform of human acetylcholinesterase in transgenic tomato plants. Active and stable acetylcholinesterase, which retains the kinetic characteristics of the human enzyme, accumulated in tomato plants. High levels of specific activity were registered in leaves (up to 25 nmol min−1 mg protein−1) and fruits (up to 250 nmol min−1 mg protein−1). © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 259–266, 2001.
Galactomannanases Man2 and Man5 from Thermotogaspecies: Growth physiology on galactomannans, gene sequence analysis, and biochemical properties of recombinant enzymes
Authors: Parker Kimberley N. , Chhabra Swapnil R. , Lam David , Callen Walter , Duffaud Guy D. , Snead Marjory A. , Short Jay M. , Mathur Eric J. , Kelly Robert M. 
Published: August 2002

AbstractThe enzymatic hydrolysis of mannan‐based hemicelluloses is technologically important for applications ranging from pulp and paper processing to food processing to gas and oil well stimulation. In many cases, thermostability and activity at elevated temperatures can be advantageous. To this end, the genes encoding β‐mannosidase (man2) and β‐mannanase (man5) from the hyperthermophilic bacteria Thermotoga neapolitana 5068 and Thermotoga maritima were isolated, cloned, and expressed in Escherichia coli. The amino acid sequences for the mannosidases from these organisms were 77% identical and corresponded to proteins with an Mr of approximately 92 kDa. The translated nucleotide sequences for the β‐mannanase genes (man5) encoded polypeptides with an Mr of 76 kDa that exhibited 84% amino acid sequence identity. The recombinant versions of Man2 and Man5 had similar respective biochemical and biophysical properties, which were also comparable to those determined for the native versions of these enzymes in T. neapolitana. The optimal temperature and pH for the recombinant Man2 and Man5 from both organisms were approximately 90°C and 7.0, respectively. The presence of Man2 and Man5 in these two Thermotoga species indicates that galactomannan is a potential growth substrate. This was supported by the fact that β‐mannanase and β‐mannosidase activities were significantly stimulated when T. neapolitana was grown on guar or carob galactomannan. Maximum cell densities increased by at least tenfold when either guar or carob galactomannan was added to the growth medium. For T. neapolitana grown on guar at 83°C, Man5 was secreted into the culture media, whereas Man2 was intracellular. These localizations were consistent with the presence and lack of signal peptides for Man5 and Man2, respectively. The identification of the galactomannan‐degrading enzymes in these Thermotoga species adds to the list of biotechnologically important hemicellulases produced by members of this hyperthermophilic genera. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 322–333, 2001.
Erythropoietin production from CHO cells grown by continuous culture in a fluidized‐bed bioreactor
Authors: Wang M‐D. , Yang M. , Huzel N. , Butler M. 
Published: August 2002

AbstractA Chinese hamster ovary (CHO) cell line that expresses human erythropoietin (huEPO) was in a 2‐L Cytopilot fluidized‐bed bioreactor with 400 mL macroporous Cytoline‐1 microcarriers and a variable perfusion rate of serum‐free and protein‐free medium for 48 days. The cell density increased to a maximum of 23 × 106 cells/mL, beads on day 27. The EPO concentration increased to 600 U/mL during the early part of the culture period (on day 24) and increased further to 980 U/mL following the addition of a higher concentration of glucose and the addition of sodium butyrate. The EPO concentration was significantly higher (at least 2x than that in a controlled stirred‐tank bioreactor, in a spinner flask, or in a stationary T‐flask culture. The EPO accumulated to a total production of 28,000 kUnits over the whole culture period. The molecular characteristics of EPO with respect to size and pattern of glycosylation did not change with scale up. The pattern of utilization and production of 18 amino acids was similar in the Cytopilot culture to that in a stationary batch culture in a T‐flask. The concentration of ammonia was maintained at a low level (< 2 mM) over the entire culture period. The specific rate of consumption of glucose, as well as the specific rates of production of lactate and ammonia, were constant throughout the culture period indicating a consistent metabolic behavior of the cells in the bioreactor. These results indicate the potential of the Cytopilot bioreactor culture system for the continuous production of a recombinant protein over several weeks. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 194–203, 2002.
Chromate/nitrite interactions in Shewanella oneidensis MR‐1: Evidence for multiple hexavalent chromium [Cr(VI)] reduction mechanisms dependent on physiological growth conditions
Authors: Viamajala Sridhar , Peyton Brent M. , Apel William A. , Petersen James N. 
Published: August 2002

AbstractInhibition of hexavalent chromium [Cr(VI)] reduction due to nitrate and nitrite was observed during tests with Shewanella oneidensis MR‐1 (previously named Shewanella putrefaciens MR‐1 and henceforth referred to as MR‐1). Initial Cr(VI) reduction rates were measured at various nitrite concentrations, and a mixed inhibition kinetic model was used to determine the kinetic parameters—maximum Cr(VI) reduction rate and inhibition constant [Vmax,Cr(VI) and Ki,Cr(VI)]. Values of Vmax,Cr(VI) and Ki,Cr(VI) obtained with MR‐1 cultures grown under denitrifying conditions were observed to be significantly different from the values obtained when the cultures were grown with fumarate as the terminal electron acceptor. It was also observed that a single Vmax,Cr(VI) and Ki,Cr(VI) did not adequately describe the inhibition kinetics of either nitrate‐grown or fumarate‐grown cultures. The inhibition patterns indicate that Cr(VI) reduction in MR‐1 is likely not limited to a single pathway, but occurs via different mechanisms some of which are dependent on growth conditions. Inhibition of nitrite reduction due to the presence of Cr(VI) was also studied, and the kinetic parameters Vmax,NO2 and Ki,NO2 were determined. It was observed that these coefficients also differed significantly between MR‐1 grown under denitrifying conditions and fumarate reducing conditions. The inhibition studies suggest the involvement of nitrite reductase in Cr(VI) reduction. Because nitrite reduction is part of the anaerobic respiration process, inhibition due to Cr(VI) might be a result of interaction with the components of the anaerobic respiration pathway such as nitrite reductase. Also, differences in the degree of inhibition of nitrite reduction activity by chromate at different growth conditions suggest that the toxicity mechanism of Cr(VI) might also be dependent on the conditions of growth. Cr(VI) reduction has been shown to occur via different pathways, but to our knowledge, multiple pathways within a single organism leading to Cr(VI) reduction has not been reported previously. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 770–778, 2002.
Biosynthesis of poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate‐co‐3‐hydroxyhexanoate) by metabolically engineered Escherichia coli strains
Authors: Park Si Jae , Ahn Woo Suk , Green Phillip R. , Lee Sang Yup 
Published: August 2002

AbstractThe recombinant Escherichia coli strain, equipped with the newly cloned Aeromonas PHA biosynthesis genes, could produce a terpolymer of 3‐hydroxybutyrate (3HB), 3‐hydroxyvalerate (3HV), and 3‐hydroxyhexanoate (3HHx) [P(3HB‐co‐3HV‐co‐3HHx)] from dodecanoic acid plus odd carbon number fatty acid. In addition, the orf1 gene of Aeromonas hydrophila was found to play a critical role in assimilating the 3HV monomer and in regulating the monomer fraction in the terpolymer. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 81–86, 2001.