bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folate‐targeted imaging of activated macrophages in rats with adjuvant‐induced arthritis
Authors: Turk Mary Jo , Breur Gert J. , Widmer William R. , Paulos Chrystal M. , Xu Le‐Cun , Grote Lee Ann , Low Philip S. 
Published: September 2002

AbstractObjectiveTo determine whether overexpression of the high‐affinity folate receptor (FR) on activated macrophages can be exploited to selectively target imaging agents to sites of inflammation in rats with adjuvant‐induced arthritis (AIA).MethodsFolic acid was conjugated to a 99mTc chelator (the complex termed EC20), and its distribution was visualized using gamma scintigraphy in healthy rats, rats with AIA, and arthritic rats that had been depleted of macrophages. To confirm that uptake was mediated by the FR, excess folic acid competition studies were conducted, and tissue FR levels were quantitated using a radioligand binding assay. Flow cytometry was also used to investigate uptake of folate conjugates into macrophages of both arthritic and healthy rats.ResultsEC20 concentrated in the arthritic extremities of diseased rats but not in the extremities of healthy rats. The intensity of images of affected tissues was greatly reduced in the presence of excess competing folic acid. The livers and spleens of arthritic animals also showed enhanced uptake of EC20 and increased levels of FR. Depletion of macrophages from arthritic animals reduced tissue FR content and concomitantly abolished uptake of EC20. In addition, macrophages isolated from livers of rats with AIA exhibited a significantly higher binding capacity for folate conjugates than did macrophages obtained from healthy rats.ConclusionAlthough EC20 is currently undergoing clinical evaluation for use in the imaging of ovarian carcinomas, the present results suggest that it may also be useful for assaying the participation of activated macrophages in inflammatory processes such as rheumatoid arthritis.
Bone loss in patients with rheumatoid arthritis: Results from a population‐based cohort of 366 patients followed up for two years
Authors: Haugeberg Glenn , Ørstavik Ragnhild E. , Uhlig Till , Falch Jan A. , Halse Johan I. , Kvien Tore K. 
Published: September 2002

AbstractObjectiveTo evaluate the extent of and risk factors for bone loss in a population‐based cohort of patients with rheumatoid arthritis (RA) receiving conventional health care.MethodsIn a longitudinal study, clinical data were collected and bone mineral density (BMD) measurements were performed at baseline and after 2 years. Dual‐energy x‐ray absorptiometry was used for hip and spine BMD measurements. At baseline, patients received advice about lifestyle adjustments and calcium and vitamin D supplementation; during the followup period they were treated with antirheumatic and bone‐sparing drugs, according to clinical judgment.ResultsAfter a mean ± SD of 2.2 ± 0.2 years, 366 (298 women, 68 men) of the 488 patients who were examined at baseline were reexamined. At that time, 47.9% were current users of corticosteroids and 37.0% were using antiresorptive drugs (hormone replacement therapy, bisphosphonates, or calcitonin). The mean BMD reduction was −0.64% in the femoral neck, −0.77% in the total hip, and −0.29% in the spine at L2‐4. BMD was increased at all measurement sites in current users of antiresorptive drugs (0.16–1.64%) but was decreased in patients using calcium and vitamin D alone (−1.99% to −1.39%) and in patients not using any osteoporosis treatment (−1.20% to −0.43%). Current use of corticosteroids was independently associated with increased risk for BMD loss in the total hip (odds ratio [OR] 2.63, 95% confidence interval [95% CI] 1.38–5.00) and spine at L2‐4 (OR 2.70, 95% CI 1.30–5.63), whereas current use of antiresorptive drugs was associated with decreased risk for bone loss in the total hip (OR 0.43, 95% CI 0.20–0.89).ConclusionResults of this population‐based, 2‐year followup study indicate that adequate management of patients with RA, addressing both the rheumatic disease and osteoporosis, protects against bone loss.
Flunisolide HFA vs flunisolide CFC: pharmacokinetic comparison in healthy volunteers
Authors: Nolting Arno , Sista Suryanarayana , Abramowitz Wattanaporn 
Published: September 2002

AbstractTwo preparations of flunisolide, an inhaled corticosteroid, were compared in a parallel, multiple‐dose study of 31 healthy volunteers. The new flunisolide preparation substitutes hydrofluoroalkane (HFA) for chlorofluorocarbon (CFC) as a propellant and incorporates a spacer into its pressurized metered‐dose inhaler (pMDI). In this study, subjects were randomly assigned to receive flunisolide CFC 1000 µg bid; flunisolide HFA 170 µg bid; or flunisolide HFA 340 µg bid. Dosing was continued for 13.5 days. Plasma samples were analyzed after the first dose on day 1 and again after 13.5 days of treatment. No significant differences in day 1 dose‐adjusted peak plasma concentrations (Cmax) were observed. Dose proportionality in Cmax and area under the concentration–time curves (AUC) was observed for the flunisolide HFA 170 and 340 µg bid groups on days 1 and 14. Day 1 mean dose‐adjusted AUC was significantly greater in the flunisolide CFC 1000 µg bid group than in either flunisolide HFA group, indicating greater systemic availability of flunisolide CFC. Oral clearance and volume of distribution were significantly higher for flunisolide CFC than for flunisolide HFA. This may be due to greater oropharyngeal deposition by the flunisolide CFC formulation. Another indicator of greater flunisolide CFC oropharyngeal deposition was observed in Cmax and AUC0–tlast values for 6β‐OH flunisolide, the first‐pass metabolite of flunisolide. The values of these pharmacokinetic parameters were significantly higher in the flunisolide CFC group than in the 340 µg bid flunisolide HFA group on days 1 and 14. However, this was not the case for cortisol values where flunisolide HFA accounted for less oropharyngeal deposition and more targeted delivery without adverse events. The study demonstrated that flunisolide HFA administered through a pMDI with built‐in spacer was safe and well tolerated in healthy volunteers. Copyright © 2001 John Wiley & Sons, Ltd.
Successful generalized parent training and failed schedule thinning of response blocking for automatically maintained object mouthing
Authors: Tarbox Jonathan , Wallace Michele D. , Tarbox Rachel S. F. 
Published: September 2002

AbstractMouthing of inedible objects maintained by automatic reinforcement can be particularly difficult to treat, given that the functional reinforcer is not socially mediated, and therefore it is difficult or impossible to withhold reinforcement. In the current investigation, response blocking was used to reduce automatically maintained object mouthing. Treatment effects were generalized to the natural environment. An attempt at schedule thinning was not successful; however, the participant's parents were trained to implement the treatment successfully in their home. Copyright © 2002 John Wiley & Sons, Ltd.
Calculability analysis in underdetermined metabolic networks illustrated by a model of the central metabolism in purple nonsulfur bacteria
Authors: Klamt Steffen , Schuster Stefan , Gilles Ernst Dieter 
Published: September 2002

AbstractMetabolite balancing has turned out to be a powerful computational tool in metabolic engineering. However, the linear equation systems occurring in this analysis are often underdetermined. If it is difficult or impossible to find the missing constraints, it is nevertheless feasible in some cases to determine the values of a subset of the unknown rates. Here, a procedure for finding out which reaction rates can be uniquely calculated in underdetermined metabolic networks and computing these rates is given. The method is based on the null space to the stoichiometry matrix corresponding to the reactions with unknown rates. It is shown that this method is considerably easier to handle than an algorithm given previously (Van der Heijden et al., 1994a). Furthermore, a useful elementary representation of the null space is presented which is closely related with the elementary flux modes. This unique representation is central to a more general approach to observability/calculability analysis. In particular, it allows one to find, in an easy way, those sets of measurable rates that enable a calculation of a certain unknown rate. Besides, rates which are never calculable by metabolite balancing may be easily detected by this method.The applicability of these methods is illustrated by a model of the central metabolism in purple nonsulfur bacteria. The photoheterotrophic growth of these representatives of anoxygenic photosynthetic bacteria is stoichiometrically analyzed. Interesting metabolic constraints caused by the necessary balancing of NAD(P)H can be detected in a highly underdetermined system. This is, to our knowledge, the first application of stoichiometric analysis to the metabolic network in this bacteria group using metabolite balancing techniques. A new software tool, the FluxAnalyzer, is introduced. It allows quantitative and structural analysis of metabolic networks in a graphical user interface. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 734–751, 2002; DOI 10.1002/bit.10153
Modeling of the biotransformation of crotonobetaine into L‐(−)‐carnitine by Escherichia coli strains
Authors: Canovas M. , Maiquez J. R. , Obón J. M. , Iborra J. L. 
Published: September 2002

AbstractA simple unstructured model, which includes carbon source as the limiting and essential substrate and oxygen as an enhancing substrate for cell growth, has been implemented to depict cell population evolution of two Escherichia coli strains and the expression of their trimethylammonium metabolism in batch and continuous reactors. Although the model is applied to represent the trans‐crotonobetaine to L‐(−)‐carnitine biotransformation, it is also useful for understanding the complete metabolic flow of trimethylammonium compounds in E. coli. Cell growth and biotransformation were studied in both anaerobic and aerobic conditions. For this reason we derived equations to modify the specific growth rate, μ, and the cell yield on the carbon source (glycerol), Yxg, as oxygen increased the rate of growth. Inhibition functions representing an excess of the glycerol and oxygen were included to depict cell evolution during extreme conditions. As a result, the model fitted experimental data for various growth conditions, including different carbon source concentrations, initial oxygen levels, and the existence of a certain degree of cell death. Moreover, the production of enzymes involved within the E. coli trimethylammonium metabolism and related to trans‐crotonobetaine biotransformation was also modeled as a function of both the cell and oxygen concentrations within the system. The model describes all the activities of the different enzymes within the transformed and wild strains, able to produce L‐(−)‐carnitine from trans‐crotonobetaine under both anaerobic and aerobic conditions. Crotonobetaine reductase inhibition by either oxygen or the addition of fumarate as well as its non‐reversible catalytic action was taken into consideration. The proposed model was useful for describing the whole set of variables under both growing and resting conditions. Both E. coli strains within membrane high‐density reactors were well represented by the model as results matched the experimental data. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 764–775, 2002; DOI 10.1002/bit.10157
Miniaturized amperometric flow immunoassay system using a glass fiber membrane modified with anion
Authors: Lim Tae‐Kyu , Imai Satoko , Matsunaga Tadashi 
Published: September 2002

AbstractThis paper describes a miniaturized amperometric flow immunoassay system using a glass fiber membrane modified with anion. The glass fiber membrane was functionally modified with γ‐glycidoxypropyltrimethoxysilane and sodium thiosulfate and was used for separation of protein. Anti‐human chorionic gonadotrophin (HCG) immunoglobulin G (IgG) antibody conjugated with ferrocenemonocarboxylic acid (Fc), namely, Fc‐conjugated IgG (Fc–IgG), was used as a novel analytical reagent. HCG and Fc–IgG complexes were separated from free Fc–IgG based on differences in isoelectric point (pI) using the glass fiber membrane modified with a thiosulfonyl acid functional group. The assay yields a linear relationship between current and HCG concentration in the range of 0–2000 mIU/mL. This simple technique enables the assay of HCG within 2 min. The modified glass fiber membrane was regenerated by occasional elution with malonate buffer (pH 6.0) containing 0.5 M NaCl, to remove free Fc–IgG. Free Fc–IgG recovered in this manner could be reused up to eight times without significant decreases in sensitivity. This miniaturized amperometric flow immunoassay requires only minute quantities of serum and generates highly reproducible results. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 758–763, 2002; DOI 10.1002/bit.10158
Inhibition of sodium butyrate‐induced apoptosis in recombinant Chinese hamster ovary cells by constitutively expressing antisense RNA of caspase‐3
Authors: Kim No Soo , Lee Gyun Min 
Published: September 2002

AbstractSodium butyrate (NaBu) can enhance the expression of genes controlled by some of the mammalian promoters, but it can also inhibit cell growth and induce cellular apoptosis. Thus, the beneficial effect of using a higher concentration of NaBu on a foreign protein expression is compromised by its cytotoxic effect on cell growth. To overcome this cytotoxic effect of NaBu, the expression vector of antisense RNA of caspase‐3 was constructed and transfected to recombinant Chinese hamster ovary (rCHO) cells producing a humanized antibody. Using this antisense RNA strategy, rCHO cells (B3) producing a low level of caspase‐3 proenzyme were established. When batch cultures of both B3 cells and control cells transfected with antisense RNA‐deficient plasmid were performed in the absence of NaBu, both cells showed similar profiles of cell growth and antibody production. Compared with control cell culture, under the condition of 5 mM NaBu addition at the exponential growth phase, expression of antisense RNA of caspase‐3 significantly suppressed the NaBu‐induced apoptosis of B3 cells and extended culture longevity by >2 days if the culture was terminated at cell viability of 50%. However, compared with control cell culture, the final antibody concentration of B3 cell culture was not increased in the presence of NaBu, which may be due to the loss of cellular metabolic capability resulted from the depolarization of mitochondrial membrane. Taken together, this study suggests that, although expression of antisense RNA of caspase‐3 does not improve antibody productivity of rCHO cells, it can suppress NaBu‐induced apoptotic cell death of rCHO cells and thereby may reduce problems associated with cellular disintegration. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 217–228, 2002; DOI 10.1002/bit.10191
Decreasing the hyphal branching rate of Saccharopolyspora erythraea NRRL 2338 leads to increased resistance to breakage and increased antibiotic production
Authors: Wardell J. N. , Stocks S. M. , Thomas C. R. , Bushell M.E. 
Published: September 2002

AbstractMutation and selection for increased resistance to cell‐wall synthesis inhibitors led to alterations in the hyphal branching rate of Saccharopolyspora erythraea NRRL 2338. Mutants with decreased branching frequency exhibited increased hyphal strength (estimated by in vitro micromanipulation). As the hyphal strength was increased, this led to a greater proportion of hyphal particles in liquid culture with a hyphal fragment diameter of greater than 88 μm. This, in turn, coincided with proportionately increased antibiotic production. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 141–146, 2002; DOI 10.1002/bit.10210
Successional development of sulfate‐reducing bacterial populations and their activities in an activated sludge immobilized agar gel film
Authors: Okabe Satoshi , Santegoeds Cecilia M. , Watanabe Yoshimasa , Beer Dirk de 
Published: September 2002

AbstractA combination of fluorescence in situ hybridization (FISH), microprofiles, and denaturing gradient gel electrophoresis (DGGE) analysis of PCR‐amplified 16S rDNA fragments followed by hybridization analysis with specific probes was applied to investigate successional development of sulfate‐reducing bacteria (SRB) community structure and in situ sulfide production activity within an activated sludge immobilized agar gel film. In this model biofilm system, since biases arising from biofilm heterogeneity can be ignored, the population dynamics of SRB in the agar gel is directly related to physiological capability and in situ activity of SRB. Microelectrode measurements showed that an anoxic zone was already developed at the beginning (0 day), a first sulfide production of 0.054 μmol H2S m−2 s−1 was detected during the first week, and the rate increased gradually to 0.221 μmol H2S m−2 s−1 in the fifth week. The most active sulfide production zone moved upward to the chemocline and intensified with time to form a narrow zone with high volumetric sulfide production rates. This result coincided with the shift of the spatial distributions of SRB populations determined by FISH. In situ hybridization with probe SRB385 for mainly general SRB of the delta Proteobacteria plus some gram‐positive bacteria and probe 660 for Desulfobulbus indicated that the most abundant populations of SRB were primarily restricted to near the oxic/anoxic interface (chemocline). A close observation of the development of the vertical distributions of SRB populations revealed that the cell numbers of Desulfobulbus tripled (from 0.5 × 108 to 1.5 × 108 cells cm−3) near the oxic/anoxic interface. Similar growth (from 1.0 ×108 to 4.5 × 108 cells cm−3) of Desulfovibrio‐like SRB that hybridized with probe SRB385 was observed. PCR‐DGGE followed by hybridization analysis revealed that one Desulfobulbus strain was detected from the beginning, and another strain appeared after 1 week, coinciding with the first detected sulfide production. In addition, three strains hybridizing with probe 687 (possibly Desulfovibrio) were also dominant SRB in the agar gel. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 119–130, 2002; DOI 10.1002/bit.10240
Process performance models in the optimization of multiproduct protein production plants
Authors: Pinto José M. , Montagna Jorge M. , Vecchietti Aldo R. , Iribarren Oscar A. , Asenjo Juan A. 
Published: September 2002

AbstractIn this work we propose a model that simultaneously optimizes the process variables and the structure of a multiproduct batch plant for the production of recombinant proteins. The complete model includes process performance models for the unit stages and a posynomial representation for the multiproduct batch plant. Although the constant time and size factor models are the most commonly used to model multiproduct batch processes, process performance models describe these time and size factors as functions of the process variables selected for optimization. These process performance models are expressed as algebraic equations obtained from the analytical integration of simplified mass balances and kinetic expressions that describe each unit operation. They are kept as simple as possible while retaining the influence of the process variables selected to optimize the plant. The resulting mixed‐integer nonlinear program simultaneously calculates the plant structure (parallel units in or out of phase, and allocation of intermediate storage tanks), the batch plant decision variables (equipment sizes, batch sizes, and operating times of semicontinuous items), and the process decision variables (e.g., final concentration at selected stages, volumetric ratio of phases in the liquid–liquid extraction). A noteworthy feature of the proposed approach is that the mathematical model for the plant is the same as that used in the constant factor model. The process performance models are handled as extra constraints. A plant consisting of eight stages operating in the single product campaign mode (one fermentation, two microfiltrations, two ultrafiltrations, one homogenization, one liquid–liquid extraction, and one chromatography) for producing four different recombinant proteins by the genetically engineered yeast Saccharomyces cerevisiae was modeled and optimized. Using this example, it is shown that the presence of additional degrees of freedom introduced by the process performance models, with respect to a fixed size and time factor model, represents an important development in improving plant design. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 451–465, 2001.
Evaluation of photobioreactor heat balance for predicting changes in culture medium temperature due to light irradiation
Authors: Morita Masahiko , Watanabe Yoshitomo , Saiki Hiroshi 
Published: September 2002

AbstractMicroalgal photosynthesis requires appropriate culture medium temperatures to achieve high photosynthetic performance and to maintain production of a high‐quality biomass product. Enclosed systems, such as our conical, helical tubular photobioreactor (HTP), can accomplish high photosynthetic efficiency and the small amount of culture medium used by these systems means that the culture medium temperature may be effectively controlled. On the other hand, because a high ratio of surface area to culture medium volume leads to rapid heating under the illumination condition and substantial heat loss at night, maintaining a suitable culture medium temperature is necessary to achieve efficient, commercially practical biomass production. In order to predict changes in the culture medium temperature caused by changes in solar irradiance and ambient temperature, it is necessary to understand the heat balance within the photobioreactor. We therefore investigated the heat balance in three major parts (photostage, degasser, and helical heat exchanger) of our conical HTP, analyzed the time‐dependent changes in medium temperature at various room temperatures and radiant energy inputs, and predicted changes in the culture medium temperature based on the characteristics of heat transfer among the three parts. Using this model, the predicted changes in culture medium temperature were very similar to the changes observed experimentally in the laboratory and under field conditions. This means that by calculating the time‐dependent changes in the culture medium temperature, based on measurements of solar energy input and ambient temperature, we should be able to estimate the energy required to maintain the culture medium temperature within a range where photosynthetic performance of microalgae is high. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 466–475, 2001.