bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of a Multichannel Microstructured Reactor for Studies of Oxidative Propane Dehydrogenation
Authors: Steinfeldt N. , Dingerdissen U. , Baerns M.
Published: March 2005

Microstructured reactors are a suitable tool to study highly exothermic reactions under approximately isothermal conditions. The catalytic material is deposited on the reactor wall in order to avoid a high pressure drop and to improve the heat transfer from the catalyst to the wall. It is shown that the oxidative dehydrogenation of propane can be carried out isothermally over a wide range of experimental conditions when microstructured reactors with a great number of parallel channels are used.
Development of Highly Active Pd‐ZnO/Al2O3 Catalysts for Microscale Fuel Processor Applications
Authors: Xia G. , Holladay J. D. , Dagle R A.. , Jones E. O. , Wang Y.
Published: March 2005

A series of alumina supported Pd‐ZnO catalysts were synthesized and studied for methanol steam reforming. Pd loading and Pd/Zn ratio were optimized to improve catalyst activities. Among all the catalysts studied, the catalyst with a Pd loading of 8.9 wt % and a Pd/Zn molar ratio of 0.38 exhibited the highest methanol conversion and the lowest CO selectivity. The significantly improved Pd‐ZnO/Al2O3 catalyst activity was one of the main factors improving the efficiency of a microscale fuel processor from 9 % to 15 %.
Concepts for Modularization and Automation of Microreaction Technology
Authors: Löbbecke S. , Ferstl W. , Panić S. , Türcke T.
Published: March 2005

Two different concepts for the modularization and automation of microreaction systems are described. The modular microreaction system FAMOS was developed on the basis of a functional toolkit concept for laboratory applications of microreaction technology. Microstructured reaction modules with suitable fluidic, analytical and electronic interfaces were designed which allow the realization of even multi‐stage microchemical processes like the sulfonation of toluene under thermally controlled conditions over the entire process. The automated microreaction system AuMμRes was developed to enable an active regulation of process parameters via a process control system to perform parameter screenings for the identification of process optima. Integrated microstructured flow‐through sensors and analytical interfaces were developed for the monitoring of relevant process parameters. Sampling devices for chromatographic analysis and inline Raman spectroscopy were integrated into the micoreaction system to gather relevant analytical information about the considered chemical process. By applying chemometric models, a qualitative and quantitative realtime monitoring of microchemical processes was established, as was demonstrated for different nitration reactions.
Application Report on Operating Cellular Process Chemistry Plants in Fine Chemical and Contract Manufacturing Industries
Authors: Schwalbe T. , Kursawe A. , Sommer J.
Published: March 2005

Only a few microreaction manufacturing plants are being operated to date. The performance of two different microreaction manufacturing plants is discussed, one in a dedicated application, the other in a multi‐purpose environment. Strategies to address the major design and operating challenges for microreactor manufacturing plants to equipartition starting material streams into parallel reaction chambers throughout manufacturing operation are provided for demanding liquid/liquid‐reactions. The importance of minimizing the pressure drop variances between different microreactors or channels by rigorous microreactor fabrication process control is described. A cost/performance balanced microreactor manufacturing strategy is suggested, and the ease of assessing trade‐off decisions is addressed for different manufacturing systems by the use of a case study involving a diffusion controlled Grignard reaction.
Analysis of Microstructured Reactor Characteristics for Process Miniaturization and Intensification
Authors: Commenge J.‐M. , Falk L. , Corriou J.‐P. , Matlosz M.
Published: March 2005

The present study investigates a number of key features of microstructured reactors and components devoted to process miniaturization and intensification. For processes involving transfer operations and/or chemical reactions, a simple model can be used to relate the process efficiency to the ratio of two characteristic times: the space time of the process fluid in the system and the characteristic time of the operation. A detailed analysis of the relationship between these characteristic times and the characteristic dimensions of the system highlights the principal operations that should most benefit from the potential of microstructured process components. The analysis is used to examine how microstructured reactors may be advantageously employed to improve process efficiency (intensification) or to reduce process size (miniaturization), as a function of the operations involved.
Production and Characteristics of Microreactors Made from Glass
Authors: Dietrich T. R. , Freitag A. , Scholz R.
Published: March 2005

For centuries, glass has been a very well‐known material. Even today new interesting applications are discovered. As described in the paper below, micro process engineering enables new approaches in the development and production of chemical compounds. Since there are many examples of aggressive chemicals which have to be handled, an inert material such as glass is of great interest.
Microwave‐Assisted Reaction Engineering: Microwave Apparatus at Mini‐Plant Scale with Online Analysis
Authors: Bierbaum R. , Nüchter M. , Ondruschka B.
Published: March 2005

A new mini‐plant setup is described with online HPLC analysis. This setup allows scale up to pilot‐plant scale and will help in transferring the advantages of microwave‐assisted syntheses to a technical scale. Also filter setup options that can be used to protect the analysis system from suspended particles or depositions are described, and show that analysis time is not significantly prolonged by the automated sampling procedure.
The Kinetic Acidity of Oligofluorobenzenes Correlated with Their Gas Phase Deprotonation Energies
Authors: Schlosser Manfred , Marzi Elena
Published: March 2005

The relative reactivities of fluorobenzene, all di‐, tri‐, and tetrafluorobenzenes and pentafluorobenzene toward sec‐butyllithium have been assessed in tetrahydrofuran at −100 °C. At this temperature no subsequent transmetalation reactions take place but those compromise the outcome of the competition experiments if the latter are conducted at −75 °C. The rates determined at −100 °C reflect the basicity differences between the naked (oligo)fluorophenyl anions to the extent of 10 %.
Intramolecular Electron Transfer between Tyrosine and Tryptophan Photosensitized by a Chiral π,π* Aromatic Ketone
Authors: Galian Raquel E. , Pastor‐Pérez Lourdes , Miranda Miguel A. , Pérez‐Prieto Julia
Published: March 2005

The photochemical reaction of Trp and Tyr and related peptides with Suprofen (SUP) as sensitizer in H2O/CH3CN (28:1 v/v) solutions has been studied by time‐resolved spectroscopy. The results show that SUP induces oxidation of both Trp and Tyr, as well as intramolecular‐ET reactions in the related peptides. The influence of photosensitizer configuration on the involved processes has been studied by using the enantiomerically pure compounds. A significant chiral recognition is observed in which the concentration of the radicals formed after triplet quenching depends on the configuration of the chiral center; the quenching process is higher when using the (R)‐SUP enantiomer.
Giant meso–meso‐Linked Porphyrin Arrays of Micrometer Molecular Length and Their Fabrication
Authors: Aratani Naoki , Takagi Akihiko , Yanagawa Yoshiki , Matsumoto Takuya , Kawai Tomoji , Yoon Zin Seok , Kim Dongho , Osuka Atsuhiro
Published: March 2005

On the basis of the AgI‐promoted coupling reaction of zinc(II)–5,15‐bis(3,5‐dioctyloxyphenyl)porphyrin Z1, chain elongation has been attempted by using a stepwise doubling approach, which provides Z2, Z4, Z8, Z16, Z32, Z64, Z128, Z256, Z384, and Z512. The porphyrin arrays up to Z128 are sufficiently soluble in CHCl3 and THF despite their very long molecular lengths and rodlike structures, while the arrays over Z128 show a significant drop in solubility and stability. The discrete porphyrin arrays thus isolated were characterized by means of 1H NMR spectroscopy, matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry, UV/Vis spectroscopy, gel‐permeation chromatography (GPC), cyclic voltammetry (CV), single‐crystal X‐ray crystallography, scanning tunneling microscopy (STM), and atomic force microscopy (AFM). Contrary to expected linear conformations of the arrays Z n (where n is the number of porphyrins), the single molecular images of Z128, Z256, and Z512 revealed largely bent structures; this finding indicates the substantial conformational flexibility of Z n. We also exploited an effective synthetic route by means of which Z n can be fabricated with a thiol‐protected aryl group to provide Z n S2 through Z n Br2, by bromination with N‐bromosuccinimide and subsequent Pd‐catalyzed Suzuki–Miyaura arylation. Finally, the reaction of Z256 provided Z512, Z768, and Z1024. Collectively, this work provides an important milestone in the preparation of sub‐microscale discrete organic molecules and the fabrication of molecular‐based materials, hence significantly contributing to device applications.
Carbohydrates as the Next Frontier in Pharmaceutical Research
Authors: Werz Daniel B. , Seeberger Peter H.
Published: March 2005

Synthetic carbohydrates and glycoconjugates are used to study their roles in biological important processes such as inflammation, cell–cell recognition, immunological response, metastasis, and fertilization. The development of an automated oligosaccharide synthesizer greatly accelerates the assembly of complex, naturally occurring carbohydrates as well as chemically modified oligosaccharide structures and promises to have major impact on the field of glycobiology. Tools such as microarrays, surface plasmon resonance spectroscopy, and fluorescent carbohydrate conjugates to map interactions of carbohydrates in biological systems are presented. Case studies of the successful application of carbohydrates as active agents are discussed, for example, fully synthetic oligosaccharide vaccines to combat tropical diseases (e.g., malaria), bacterial infections (e.g., tuberculosis), viral infections such as HIV, and cancer. Aminoglycosides serve as examples of drugs acting through carbohydrate–nucleic‐acid interactions, while heparin works by carbohydrate–protein interactions. A general, modular strategy for the complete stereoselective synthesis of defined heparin oligosaccharides is presented. A carbohydrate‐functionalized fluorescent polymer has been shown to detect miniscule amounts of bacteria faster than commonly used methods.
Donor‐Substituted Cyanoethynylethenes: π‐Conjugation and Band‐Gap Tuning in Strong Charge‐Transfer Chromophores
Authors: Moonen Nicolle N. P. , Pomerantz William C. , Gist Robin , Boudon Corinne , Gisselbrecht Jean‐Paul , Kawai Tsuyoshi , Kishioka Atsushi , Gross Maurice , Irie Masahiro , Diederich François
Published: March 2005

An extensive series of silyl‐protected cyanoethynylethenes (CEEs) and N,N‐dimethylanilino donor‐substituted CEEs have been synthesized. More extended chromophores were constructed by selective silyl deprotection and subsequent oxidative acetylenic coupling. The strong electron‐accepting nature of the CEEs was revealed by a combination of 13C NMR spectroscopic and electrochemistry measurements. Donor‐substituted CEEs display strong intramolecular charge‐transfer (CT) character, resulting in intense, bathochromically shifted CT bands in the UV/Vis spectrum. Their structural diversity establishes them as suitable models for the study of π‐conjugation and band gap tuning in strong charge‐transfer chromophores. The extent of π‐conjugation in the donor‐substituted CEEs was investigated by a combination of ground‐state techniques, such as X‐ray crystallography, electrochemistry, B3 LYP calculations, and NMR spectroscopy. The comparison of these ground‐state results with the features observed in the UV/Vis spectra reveals that—contrary to expectations—more extensive π‐conjugation can lead to larger band gaps in molecules with strong donor and acceptor moieties.
Screening women at high risk for breast cancer with mammography and magnetic resonance imaging
Authors: Lehman Constance D. , Blume Jeffrey D. , Weatherall Paul , Thickman David , Hylton Nola , Warner Ellen , Pisano Etta , Schnitt Stuart J. , Gatsonis Constantine , Schnall Mitchell ,   for the International Breast MRI Consortium Working Group
Published: March 2005

BACKGROUND

The authors compared the performance of screening mammography versus magnetic resonance imaging (MRI) in women at genetically high risk for breast cancer.

METHODS

The authors conducted an international prospective study of screening mammography and MRI in asymptomatic, genetically high‐risk women age ≥ 25 years. Women with a history of breast cancer were eligible for a contralateral screening if they had been diagnosed within 5 years or a bilateral screening if they had been diagnosed > 5 years previously. All examinations (MRI, mammography, and clinical breast examination [CBE]) were performed within 90 days of each other.

RESULTS

In total, 390 eligible women were enrolled by 13 sites, and 367 women completed all study examinations. Imaging evaluations recommended 38 biopsies, and 27 biopsies were performed, resulting in 4 cancers diagnosed for an overall 1.1% cancer yield (95% confidence interval [95%CI], 0.3–2.8%). MRI detected all four cancers, whereas mammography detected one cancer. The diagnostic yield of mammography was 0.3% (95%CI, 0.01–1.5%). The yield of cancer by MRI alone was 0.8% (95%CI, − 0.3–2.0%). The biopsy recommendation rates for MRI and mammography were 8.5% (95%CI, 5.8–11.8%) and 2.2% (95%CI, 0.1–4.3%).

CONCLUSIONS

Screening MRI in high‐risk women was capable of detecting mammographically and clinically occult breast cancer. Screening MRI resulted in 22 of 367 of women (6%) who had negative mammogram and negative CBE examinations undergoing biopsy, resulting in 3 additional cancers detected. MRI also resulted in 19 (5%) false‐positive outcomes, which resulted in benign biopsies. Cancer 2005. © 2005 American Cancer Society.
Serum parathyroid hormone‐related peptide is associated with systemic inflammation and adverse prognosis in gastroesophageal carcinoma
Authors: Deans Chris , Wigmore Stephen , Paterson‐Brown Simon , Black James , Ross James , Fearon Kenneth C. H.
Published: March 2005

BACKGROUND

Parathyroid hormone‐related peptide (PTHrP) is a tumor‐derived circulating factor that has been associated with hypercalcemia of malignancy. The role of PTHrP as a prognostic indicator remains unclear. Studies suggest that it may function as a growth factor; and, recently, the ability of PTHrP to induce cytokine expression has been described. PTHrP also has been proposed as a procachectic factor. In this study, the authors investigated the prognostic value of PTHrP in patients who had gastroesophageal carcinoma without hypercalcemia and determined whether PTHrP was associated with systemic inflammation and adverse nutritional status.

METHODS

Patients were recruited at the time of diagnosis. Serum was collected for determination of c‐terminal fragment PTHrP (cPTHrP) levels (by radioimmunoassay) and calcium levels as well as levels of serum cytokines and acute‐phase proteins (with an enzyme‐linked immunosorbent assay). Nutritional assessment of patients was undertaken at the same time as serum collection. Patients underwent routine staging, and survival duration was recorded.

RESULTS

One hundred fifty‐one patients with esophagogastric carcinoma were recruited. Six of 151 patients (4.0%) patients were hypercalcemic, and 26 patients (17.2%) had elevated serum cPTHrP levels. There was no association between the cPTHrP level and either serum calcium concentrations (P = 0.72) or adverse nutritional status. Elevated cPTHrP, however, was associated with significantly higher serum levels of soluble tumor necrosis factor receptor (P = 0.008) and with significantly lower levels of transferrin (P = 0.009) and albumin (P = 0.02). There was also a weak association with C‐related protein levels (P = 0.06). Elevated cPTHrP levels also were associated with an adverse prognosis, as determined by reduced survival duration, on univariate analysis (P = 0.038), but not on multivariate analysis (P = 0.15).

CONCLUSIONS

Elevated serum cPTHrP levels were present in approximately 17% of patients with gastroesophageal carcinoma in the absence of hypercalcemia and was associated with markers of systemic inflammation and with an adverse prognosis. Cancer 2005. © 2005 American Cancer Society.
A Phase I clinical trial of ixabepilone (BMS‐247550), an epothilone B analog, administered intravenously on a daily schedule for 3 days
Authors: Zhuang Sen H. , Agrawal Manish , Edgerly Maureen , Bakke Susan , Kotz Herb , Thambi Paul , Rutt Ann , Balis Frank M. , Bates Susan , Fojo Tito
Published: March 2005

BACKGROUND

The epothilones are a novel class of microtubule‐stabilizing agents. Ixabepilone (BMS‐247550; NSC 710428) is a semisynthetic analog of the natural product epothilone B. The authors conducted a Phase I study by administering ixabepilone to patients as a 1‐hour intravenous infusion daily for 3 consecutive days every 21 days.

METHODS

Twenty‐six patients were enrolled and received ixabepilone at a starting dose of 8 or 10 mg/m2 per day for 3 consecutive days.

RESULTS

One hundred and nineteen cycles were administered to 26 patients. The maximum‐tolerated dose was 8 mg/m2 per day of ixabepilone administered as a 1‐hour intravenous infusion daily for 3 consecutive days every 21 days. The dose‐limiting toxicity (DLT) was neutropenia. Other nonhematologic Grade 3 toxicities included fatigue (3 cycles), hyponatremia (1 cycle), anorexia (1 cycle), ileus (1 cycle), stomatitis (1 cycle), and emesis (1 cycle). Prolonged disease stabilization was observed in patients with mesothelioma, ovarian carcinoma, and renal cell carcinoma.

CONCLUSIONS

The recommended Phase II dose of ixabepilone on the daily schedule for 3 days was 8–10 mg/m2 per day. Neutropenia was the DLT. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting. Cancer 2005. Published 2005 by the American Cancer Society.
Refractive index measurement in viable cells using quantitative phase‐amplitude microscopy and confocal microscopy
Authors: Curl Claire L. , Bellair Catherine J. , Harris Trudi , Allman Brendan E. , Harris Peter J. , Stewart Alastair G. , Roberts Ann , Nugent Keith A. , Delbridge Lea M. D.
Published: March 2005

Background

The refractive index (RI) of cellular material provides fundamental biophysical information about the composition and organizational structure of cells. Efforts to describe the refractive properties of cells have been significantly impeded by the experimental difficulties encountered in measuring viable cell RI. In this report we describe a procedure for the application of quantitative phase microscopy in conjunction with confocal microscopy to measure the RI of a cultured muscle cell specimen.

Methods

The experimental strategy involved calculation of cell thickness by using confocal optical sectioning procedures, construction of a phase map of the same cell using quantitative phase microscopy, and selection of cellular regions of interest to solve for the cell RI.

Results

Mean cell thickness and phase values for six cell regions (five cytoplasmic and one nuclear) were determined. The average refractive index calculated for cytoplasmic and nuclear regions was 1.360 ± 0.004. The uncertainty in the final RI value represents the technique measurement error.

Conclusions

The methodology we describe for viable cell RI measurement with this prototype cell has broad generic application in the study of cell growth and functional responses. The RI value we report may be used in optical analyses of cultured cell structure and morphology. © 2005 Wiley‐Liss, Inc.
NOR expression increases on metaphase chromosomes of down syndrome lymphocytes in concordance with mitogen concentration in culture medium
Authors: Imamoglu Nalan , Demirtas Halil , Donmez‐Altuntas Hamiyet , Hamurcu Zuhal , Ilten Ali
Published: March 2005

Background

Regulation of nucleolus organizer region (NOR) expression in trisomy 21 (Down syndrome [DS]) cells is not fully explained. This work compared NOR expression on metaphase chromosomes in gradiently stimulated lymphocytes from DS patients with those from healthy controls.

Method

Conventional peripheral blood culture (72 h) and chromosomal preparation procedures were used except that blood samples from each individual were cultivated in the same but gradiently increasing concentrations (0.37, 0.75, 1.48, and 2.21 ml) of phytohemagglutinin (PHA) per 100 ml of medium. One hundred consecutive metaphases per concentration were analyzed for scoring the means of the active NORs bearing chromosomes (AgNOR+ chromosome) per individual and per concentration.

Results

In contrast to healthy controls (n = 24), AgNOR+ chromosomal number in lymphocytes from 30 DS patients increased in concordance to the gradient of PHA concentration in the culture medium.

Conclusion

DS lymphocytes do not downregulate their NOR expression in the limit of control cells. This in vitro result may serve as a clue for the explanation of the DS phenotype due to the wasted energy in producing unnecessary rRNA transcripts and AgNOR proteins in utero during organogenesis. These results also indicate that precautions must be used in routine work of NOR evaluation/interpretation in DS lymphocytes. © 2005 Wiley‐Liss, Inc.
A multicenter evaluation of the PanLeucogating method and the use of generic monoclonal antibody reagents for CD4 enumeration in HIV‐infected patients in Thailand
Authors: Pattanapanyasat Kovit , Shain Hla , Noulsri Egarit , Lerdwana Surada , Thepthai Charin , Prasertsilpa Varipin , Likanonsakul Sirirat , Yothipitak Prakit , Nookhai Somboon , Eksaengsri Achara
Published: March 2005

Background

The current method of CD4 enumeration in Thailand, based on the three‐tube, three‐color method recommended by the Centers for Disease Control and Prevention, is expensive and thus unavailable to most patients who have the human immunodeficiency virus (HIV). Less expensive, simpler protocols (i.e., PanLeucogating and primary CD4 gating) have been described but require more published validation data to gain widespread acceptance. We describe a multicenter evaluation of the PanLeucogating method.

Methods

The PanLeucogating method using generic reagents was evaluated in comparison with the standard three‐tube, three‐color method using commercial reagents. Percentage of CD4+ T cells among lymphocytes and absolute CD4+ T‐cell counts were determined in 611 HIV‐infected individuals recruited from four sites. Linear regression and Bland‐Altman tests were used for statistical analysis.

Results

The correlation of percentage of CD4+ T cells and absolute CD4+ T‐cell counts obtained with the PanLeucogating strategy and the standard predicate method was high (r2 = 0.96 and 0.95, respectively, for the entire study population and r2 > 0.95 and 0.93, respectively, for each study group). Absolute CD4+ T‐cell counts of the overall study pool and of the two subdivisions of absolute CD4+ T‐cell counts (i.e., 0–250 cells/μl and >250 cells/μl) derived from the two methods demonstrated excellent agreement, with mean biases of +18 cells/μl, +11 cells/μl, and +24 cells/μl, respectively.

Conclusions

These observations demonstrate that CD4 enumeration by PanLeucogating is reliable and can be performed to an identical standard in a quality‐assured network of collaborating laboratories as a new cost‐effective approach to HIV monitoring. © 2005 Wiley‐Liss, Inc.
Improved detection of minimal acute myeloid leukemia cells by the use of the combined parameters of XE‐2100 hematology analyzer
Authors: Tohyama Kaoru , Shiga Shuichi , Itose Yuji , Uchihashi Kinya , Ohkura Mitsugi , Takahashi Keiko , Itoh Mitsuru , Ichiyama Satoshi , Hamaguchi Yukio
Published: March 2005

Background

For the diagnosis and therapy of acute leukemia, it is important to detect a small number of leukemic cells precisely. Although several automated hematology analyzers that carry blast‐detecting programs have been developed, they do not exert sufficient detection sensitivity to exceed the sensitivity of manual eye counting method.

Methods

We constructed a new blast‐detecting program by combining the numerical information acquired from five cytometric parameters presented by XE‐2100. The sensitivity and specificity of this blast multi‐scoring program were assessed in comparison with the Blasts flag program equipped originally in XE‐2100.

Results

The blast‐detecting sensitivity was found to be highly improved in the blast multi‐scoring program as compared with the Blasts flag program without much decreasing the specificity. A small number of leukemic myeloblasts was detected at the better sensitivity than the eye counting method in the clinical course of the patients with acute myeloid leukemia.

Conclusions

The daily practical use of this blast multi‐scoring program will surely contribute to sensitive, objective, and real‐time evaluation of the control of acute myeloid leukemia with a low cost. © 2005 Wiley‐Liss, Inc.
Emission factors for asphalt‐related emissions in roofing manufacturing
Authors: Trumbore David , Jankousky Angela , Hockman Edwin L. , Sanders Ronald , Calkin John , Szczepanik Steve , Owens Roy
Published: March 2005

The vast majority of all residential construction in the United States is roofed with asphalt shingles, and asphalt products are also used extensively for commercial roofing. These roofing products are made in roughly 100 manufacturing facilities, by processing about six million tons of asphalt per year. The Asphalt Roofing Manufacturing Association (ARMA) has developed emission factors for asphalt‐related air emissions for all relevant processes in the manufacture of roofing asphalt and fiberglass based roofing products. These processes include asphalt blowing, asphalt storage, and the coating of fiberglass mat with filled asphalt. The emission factors are based on measurements in more than 20 facilities around the country. They replace old, very limited data currently available from the US EPA in their AP‐42 document. In some cases, as with particulate emissions from asphalt blowing, the new emission factors are much lower than the current AP‐42 factors. In other cases, emissions not included in AP‐42 are recognized to be significant, as with SOx emissions from asphalt blowing. Both criteria and hazardous air pollutant (HAP) emissions are covered in this compilation. Roofing asphalt processes are shown to be a very minor contributor to polyaromatic hydrocarbon (PAH) emissions. These data have been submitted to the US EPA for their consideration, and the HAP data presented here constituted the basis for the EPA MACT rulemaking for this industry. © 2005 American Institute of Chemical Engineers Environ Prog, 2005
Oxidation and absorption of nitric oxide in a packed tower with sodium hypochlorite aqueous solutions
Authors: Chen Luke , Hsu Chung‐Hao , Yang Chen‐Lu
Published: March 2005

The oxidation and absorption of nitric oxide (NO) with sodium hypochlorite aqueous (NaClO) solutions were studied to develop a two‐stage chemical scrubbing system for NOx control. In the second stage, the most practical medium for NO2 absorption is sodium sulfite aqueous solution. Although a few two‐stage systems have been installed, there are major gaps in developing NaClO aqueous solutions for NO oxidation in the first stage. Of particular importance is the lack of reliable information on rates of the chemical oxidation. A pilot‐scale research program is initiated to evaluate the oxidation rate of NO with NaClO aqueous solutions in a packed tower. The research is directed toward obtaining the height of a transfer unit (HTU) for NO oxidation and acquiring reasonable operating conditions for the packed‐bed scrubbing system. At pH 5.3, NaClO is an excellent scrubbing medium. The results are consistent with hypochlorous acid (HClO) being the oxidizing agent in the solution. The results also indicate that the liquid mass flow rate is a minor parameter that affects the NO oxidation and absorption in the scrubber. A NaClO concentration of >0.8% is crucial for high NO oxidation. © 2005 American Institute of Chemical Engineers Environ Prog, 2005
Stem/progenitor cell proliferation factors FGF‐2, IGF‐1, and VEGF exhibit early decline during the course of aging in the hippocampus: Role of astrocytes
Authors: Shetty Ashok K. , Hattiangady Bharathi , Shetty Geetha A.
Published: March 2005

Dentate neurogenesis, important for learning and memory, declines dramatically by middle age. Although studies have shown that this age‐related decrease can be reversed to some extent by exogenous applications of mitogenic factors, it is unclear whether one or more of these factors exhibits decline by middle age. We hypothesize that multiple stem/progenitor cell proliferation factors exhibit early decline during the course of aging in the hippocampus, and some of these declines are linked to age‐related alterations in hippocampal astrocytes. We measured the concentrations of fibroblast growth factor‐2 (FGF‐2), insulin‐like growth factor‐1 (IGF‐1), and vascular endothelial growth factor (VEGF) in the hippocampus of young, middle‐aged, and aged F344 rats, using enzyme‐linked immunosorbent assay (ELISA). In addition, we quantified the total number of FGF‐2 immunopositive (FGF‐2+) and glial fibrillary acidic protein immunopositive (GFAP+) cells in the dentate gyrus and the entire hippocampus. Our results provide new evidence that the concentrations of FGF‐2, IGF‐1, and VEGF decline considerably by middle age but remain steady between middle age and old age. Further, decreased concentrations of FGF‐2 during aging are associated with decreased numbers of FGF‐2+ astrocytes. Quantification of GFAP+ cells, and GFAP and FGF‐2 dual immunostaining analyses, reveal that aging does not decrease the total number of astrocytes but fractions of astrocytes that express FGF‐2 decline considerably by middle age. Thus, dramatically decreased dentate neurogenesis by middle age is likely linked to reduced concentrations of FGF‐2, IGF‐1, and VEGF in the hippocampus, as each of these factors can individually influence the proliferation of stem/progenitor cells in the dentate gyrus. Additionally, the results demonstrate that decreased FGF‐2 concentration during aging is a consequence of age‐related impairment in FGF‐2 synthesis by astrocytes. © 2005 Wiley‐Liss, Inc.
Induction of blood‐brain barrier properties in cultured brain capillary endothelial cells: Comparison between primary glial cells and C6 cell line
Authors: Boveri Monica , Berezowski Vincent , Price Anna , Slupek Stephanie , Lenfant Anne‐Marie , Benaud Christelle , Hartung Thomas , Cecchelli Romeo , Prieto Pilar , Dehouck Marie‐Pierre
Published: March 2005

The communication between glial cells and brain capillary endothelial cells is crucial for a well‐differentiated blood‐brain barrier (BBB). It has been suggested that in vitro primary glial cells (GCs) be replaced by the glial C6 cell line to standardise the model further. This study compares directly the structural and functional differentiation of bovine brain capillary endothelial cells (BBCECs) induced by co‐culture with rat primary GCs or C6 cells, for the first time. Trans‐endothelial electrical resistance (TEER) measurements showed that under no condition were C6 cells able to reproduce TEER values as high as in the presence of GCs. At the same time, permeability of the BBCECs to both radioactive sucrose and FITC‐inulin was 2.5‐fold higher when cells were co‐cultured with C6 than with GCs. Furthermore, immunocytochemistry studies showed different cell morphology and less developed tight junction pattern of BBCECs co‐cultured with C6 toward GCs. Additionally, studies on P‐glycoprotein (P‐gp) showed much lower P‐gp presence and activity in BBCECs co‐cultured with C6 than GCs. Both VEGF mRNA expression and protein content were dramatically increased when compared with GCs, suggesting that VEGF could be one of the factors responsible for higher permeability of BBB. Our results clearly indicate that, in the presence of the glial C6 cell line, BBCECs did not differentiate as well as in the co‐culture with primary GCs at both structural and functional levels. © 2005 Wiley‐Liss, Inc.
Purkinje cell dendrites grow in alignment with Bergmann glia
Authors: Lordkipanidze Tamar , Dunaevsky Anna
Published: March 2005

The pattern of growth of Purkinje cell dendrites has been analyzed and related to their interactions with Bergmann glial radial processes. In cerebellar slice cultures from mice expressing green fluorescent protein (GFP) under the glial fibrillary acidic protein (GFAP) promoter, Purkinje cells were transfected and imaged with two‐photon microscopy over 2 days. We report that while the Purkinje cell dendritic tree grows, individual dendrites increase or decrease in length. Importantly, we demonstrate that vertical growth of Purkinje cell dendrites occurs primarily in alignment with radial glial processes. These findings suggest that radial glial processes provide a structural substrate for the directional growth of Purkinje cell dendrites, thus influencing the shape of the dendritic tree. © 2005 Wiley‐Liss, Inc.
Melatonin potentiates flavone‐induced apoptosis in human colon cancer cells by increasing the level of glycolytic end products
Authors: Wenzel Uwe , Nickel Alexander , Daniel Hannelore
Published: March 2005

Melatonin is a natural compound synthesized by a variety of organs. It has been described to possess cell protecting activity in normal cells but was shown to induce apoptotic cell death in cancer cells. We determined to which extent and based on which molecular mechanisms melatonin is able to cause apoptosis in HT‐29 human colon cancer cells. Induction of apoptosis was assessed by caspase‐3‐like activity, nuclear fragmentation and chromatin condensation. Melatonin, when given alone at a concentration of 1 mM, did not affect any of the apoptosis markers. It potentiated apoptosis induced by the flavonoid flavone significantly. Whereas flavone alone at a concentration of 150 μM led to a 8‐fold increase in caspase‐3‐like activity associated with around 40% of cells displaying DNA‐fragmentation, a combination of flavone and melatonin increased caspase‐3‐like activity 30‐fold and 80% of cells exhibited fragmentation of DNA when compared to untreated controls. Melatonin caused an increase in cytosolic lactate levels that most likely allows the flavone‐induced activation of the mitochondrial pyruvate/lactate importer to deliver more substrates to mitochondrial respiration. The subsequent increased production of mitochondrial O2− · in the presence of flavone was further increased by melatonin. Scavenging mitochondrial O2−. by benzoquinone or blocking the lactate/pyruvate transporter by 5‐nitro‐2‐(3‐phenylpropylamino) benzoate inhibited mitochondrial O2−.‐generation and apoptosis execution mediated by flavone and melatonin. Our study provides evidence that melatonin potentiates flavone‐induced apoptosis in HT‐29 human colon cancer cells by enhancing the level of oxidizable substrates that can be transported into mitochondria in the presence of flavone. © 2005 Wiley‐Liss, Inc.
Recombinant adeno‐associated virus‐mediated TRAIL gene therapy suppresses liver metastatic tumors
Authors: Ma Hong , Liu Yanxin , Liu Shilian , Kung Hsiang‐Fu , Sun Xueying , Zheng Dexian , Xu Ruian
Published: March 2005

To evaluate the tumoricidal activity of tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) on disseminated liver metastatic tumors, we constructed a recombinant adeno‐associated virus (rAAV) expressing the extracellular domain (95–281aa) of human TRAIL (TRAIL95–281, and the recombinant virus was designated as rAAV‐TRAIL) using the 3‐plasmid, helper‐virus‐free, packaging system. Transduction of mouse lymphoma EL‐4 cells and Jurkat T cells lead to the expression of TRAIL95–281 protein in both virus‐transduced cells and the culture media, along with apoptosis of these cells in vitro. The therapeutic potential of rAAV‐TRAIL was then evaluated in an orthotopic transplanted mouse model mimicking liver cancer metastasis, which was established by injection of EL‐4 cells into the liver of C57BL/6 mice via the hepatic portal veins. Subsequent intraportal vein injection of rAAV‐TRAIL, not the control virus, into the liver of these mice resulted in significant suppression of tumor growth and prolonged survival, while normal hepatocyte toxicity is undetectable. Histological and biochemical analysis in tumor tissue and serum confirmed that TRAIL95–281 was stably expressed in relatively high level in hepatocytes and was secreted into the serum in active trimeric form. Futhermore, the mechanism for rAAV‐TRAIL to inhibit tumor growth was by inducing apoptosis of the tumor cells metastasizing to the livers. These results strongly suggest that the rAAV‐TRAIL‐mediated gene delivery could be a promising approach for the treatment of liver metastasis cancer. © 2005 Wiley‐Liss, Inc.
Activation of human cancer/testis antigen gene, XAGE‐1, in tumor cells is correlated with CpG island hypomethylation
Authors: Lim Jun Hee , Kim Sang‐Pyo , Gabrielson Edward , Park Yong Bok , Park Jong‐Wook , Kwon Taeg Kyu
Published: March 2005

Expression of the XAGE‐1 antigen is restricted to germ cells of the testis and a variety of neoplastic tissues. To date, the molecular mechanism for regulating expression of this cancer/testis antigen gene has been unknown. To evaluate methylation as a potential mechanism for regulating expression of this gene, we first correlated gene methylation status (measured by sequencing of bisulfide‐modified DNA and COBRA) to expression of XAGE‐1 mRNA in normal and cancerous cells. This analysis revealed dense methylation of the CpG island in the XAGE‐1 gene promoter for the normal and cancerous cells that do not express this gene but loss of this methylation in normal testis, cancer cell lines and the primary gastric cancers where the gene is highly expressed. Further supporting the role of methylation in regulating expression of XAGE‐1 were observations that treatment of 2 heavily methylated cell lines, SNU620 and HT29, with 5′‐aza‐deoxycytidine resulted in demethylation of XAGE‐1 promoter and corresponding expression of this gene. Finally, we cloned various segments of the CpG‐rich XAGE‐1 gene promoter linked to a luciferase reporter construct and transiently transfected this construct into HCT116 cells. These experiments confirmed transcriptional regulatory activity for the promoter region that incorporates the CpG island and demonstrated that in vitro methylation of this island results in loss of promoter activity. Collectively, these studies indicate that XAGE‐1 expression in normal and cancerous tissues is regulated by methylation of the CpG island in the gene promoter. © 2005 Wiley‐Liss, Inc.
Oral squamous cell carcinoma cells induce osteoclast differentiation by suppression of osteoprotegerin expression in osteoblasts
Authors: Tada Takeyuki , Jimi Eijiro , Okamoto Masato , Ozeki Satoru , Okabe Koji
Published: March 2005

The invasion of oral squamous cell carcinoma (SCC) cells into the mandibular bone is a common clinical problem. It has been reported that BHY cells, a human oral SCC cell line, are capable of invading mandibular bone of nude mice. These results led us to examine possible mechanisms of osteoclastogenesis induced by BHY cells using in vitro culture systems. When BHY cells were cocultured with mouse bone marrow cells (BMCs), only few osteoclasts were formed, even though BHY cells express the receptor activator of NF‐κB ligand (RANKL). However, adding BHY cells to a coculture of mouse primary osteoblasts (POBs) and BMCs markedly induced osteoclastogenesis in the absence of osteotropic factors. Furthermore, another oral SCC cell line, HSC‐2, which does not express RANKL, also induced osteoclastogenesis in our cocultures. These effects were significantly, but not completely, inhibited by adding osteoprotegerin (OPG). In addition, we also found that TNFα released from these cells partially contributes to osteoclastogenesis via a RANKL‐independent mechanism. Adding BHY or HSC‐2 cells suppressed mouse OPG mRNA expression and protein production by POBs in cocultures of POBs and human oral SCC cells. This finding is consistent with the result that BHY cells and HSC‐2 cells did not enhance osteoclastogenesis in cocultures of BMCs and POBs from OPG‐deficient mice. Immunohistochemical analysis showed a reduction of OPG expression in osteolytic lesions as compared to normal lesions from oral SCC patients. Therefore, oral SCC‐induced suppression of OPG expression in POBs appears critical for osteoclastogenesis, rather than expression of RANKL in SCC cells. © 2005 Wiley‐Liss, Inc.
Herceptin‐induced inhibition of ErbB2 signaling involves reduced phosphorylation of Akt but not endocytic down‐regulation of ErbB2
Authors: Longva Karianne E. , Pedersen Nina Marie , Haslekås Camilla , Stang Espen , Madshus Inger H.
Published: March 2005

The anti‐proliferative effect of the ErbB2 specific antibody Herceptin in cells overexpressing ErbB2 has previously been explained by endocytic downregulation of ErbB2. However, in the following, we demonstrate that Herceptin inhibited proliferation of ErbB2 overexpressing cells without downregulating ErbB2. Herceptin did also not induce endocytosis of ErbB2. Herceptin was found to blunt proliferation of SKBr3 cells overexpressing EGFR, ErbB2, and ErbB3 and expressing functional PTEN, probably by recruiting PTEN to the plasma membrane. Akt was found to be constitutively phosphorylated both in SKBr3 cells overexpressing EGFR, ErbB2 and ErbB3, and in SKOv3 cells, overexpressing EGFR and ErbB2. However, phosphorylation of Akt was inhibited by Herceptin only in SKBr3 cells. SKOv3 cells, which lack the tumour suppressor protein Ras homolog member I, was found to have constitutively phosphorylated mitogen activated protein kinase and functionally increased Ras activity. SKOv3 cells further had low expression levels of PTEN. We thus confirm that the anti‐proliferative effect of Herceptin in SKBr3 cells is due to recruitment of PTEN to the plasma membrane and conclude that Herceptin does not blunt phosphatidyl inositol 3 kinase‐induced growth in cells with constitutive Ras activity. We further conclude that endocytic downregulation of ErbB2 does not contribute to Herceptin's antiproliferative effect. © 2005 Wiley‐Liss, Inc.
Polymorphisms of XRCC1 gene, alcohol consumption and colorectal cancer
Authors: Hong Yun‐Chul , Lee Kwan‐Hee , Kim Woo‐Chul , Choi Sun‐Keun , Woo Ze‐Hong , Shin Soo‐Kyung , Kim Ho
Published: March 2005

To evaluate contribution of polymorphisms of the XRCC1 gene to the risk of colorectal cancer, we conducted a case‐control study of 209 colorectal cancer cases and 209 age‐ and gender‐matched controls in the Korean population. We tested the hypothesis by constructing allele combinations with known SNP. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in lymphocyte DNA by PCR‐RFLP. We observed an increased risk of colorectal cancer associated with the 399Gln allele. The odds ratio (OR) was 1.61 (95% confidence interval [CI] 1.09–2.39) for the 399Gln allele. When combined allele‐specific OR were calculated after estimating frequencies, 3 common allele combinations were found to be associated with an increased risk of colorectal cancer. The OR for the 194Trp‐280Arg‐399Arg was 1.48 (95% CI = 1.06–2.07) using 194Arg‐280Arg‐399Arg as the reference. The OR for the 194Arg‐280His‐399Arg and the 194Arg‐280Arg‐399Gln were 1.78 (95% CI = 1.09–2.89) and 1.78 (95% CI = 1.23–2.59), respectively. Analysis after controlling for smoking, exercise and dietary habits indicated that alcohol consumption (≥80 g/week) is a significant risk factor of colorectal cancer (OR = 2.60, 95% CI = 1.46–4.62). An increased risk for colorectal cancer was identified in alcohol drinkers with the risky allele combinations. Our results suggest that polymorphisms in the XRCC1 genes may contribute to colorectal cancer susceptibility, and some evidence was obtained of a genetic modification for the relationship between alcohol intake and colorectal cancer. © 2005 Wiley‐Liss, Inc.
Ewing tumours and synovial sarcomas have critical features of karyotype evolution in common with epithelial tumours
Authors: Höglund Mattias , Gisselsson David , Mandahl Nils , Mitelman Felix
Published: March 2005

We have analysed the accumulated cytogenetic data on karyotypic evolution in Ewing tumours (ET) and synovial sarcomas (SS). Both tumour types frequently show balanced translocations, t(11;22) and t(X;18), respectively, that result in specific fusion genes. The analyses revealed +8, +12, +1q, and 16q− as important secondary changes to t(11;22) in ET and the imbalances showed a distinct temporal order. By principal component analysis, one major karyotypic pathway dominated by gains and one minor dominated by losses were identified. The kartyotypic evolution pattern in SS was less distinct. Both ET and SS showed a power law distribution of the number of acquired aberrations, which in both tumour types conformed to a distribution with an exponent equal to 1. Similar distributions are frequently found in epithelial tumours. ET and SS differ in this respect from other malignancies with balanced translocations resulting in fusion genes, which typically show a power law distribution of the number of acquired aberrations with exponents close to 2. This suggests that chromosome changes in ET and SS may develop through mechanisms more similar to those in epithelial tumours lacking recurrent balanced rearrangements than in haematological malignancies characterised by balanced translocations leading to fusion genes. © 2005 Wiley‐Liss, Inc.
Phenotypic persistence after reoxygenation of hypoxic neuroblastoma cells
Authors: Holmquist Linda , Jögi Annika , Påhlman Sven
Published: March 2005

Fast‐growing solid tumors are usually insufficiently vascularized, leading to areas with necrosis and/or poorly oxygenated cells. Tumor cells adapt to acute hypoxic stress. Central to this adaptation are the hypoxia‐inducible transcription factors (HIFs), which are degraded at normoxic but become stabilized at hypoxic conditions. Hypoxic (1% O2) neuroblastoma cells downregulate sympathetic nervous system marker genes, whereas neural crest cell markers are upregulated, suggesting that hypoxic tumor cells adopt a less mature phenotype, which in the clinical setting would translate to more aggressive tumors with increased metastatic potential. Here, we compared gene expression patterns in neuroblastoma cells grown at 1%, 5% (a physiologic oxygen level) and 21% O2. At 5% O2, cells developed a weak hypoxic phenotype and HIF‐2 α, but not HIF‐1 α, was acutely stabilized. At 1% O2, HIF‐2 α protein remained present in long‐term cultures, while HIF‐1 α was present only transiently. The stability of the hypoxia‐induced dedifferentiated phenotype in cells acutely reoxygenated at either 21% or 5% O2 persisted for at least 24 hr. Genes associated with a differentiated state, like NPY, ChrA and ChrB, were still downregulated and hypoxia‐induced genes, like TH and Id2, remained upregulated. Thus, if these culture conditions are viewed as models for acute reoxygenation of metastasizing hypoxic tumor cells, our data suggest that an aggressive hypoxic phenotype persists for 24 hr or more, which might be long enough for the cells to be able to home to secondary sites, in part as a consequence of their immature hypoxic characteristics. © 2005 Wiley‐Liss, Inc.