bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of (.+‐.)‐Glaucine and (.+‐.)‐Neospirodienone via a One‐Pot Bischler—Napieralski Reaction and Oxidative Coupling by a Hypervalent Iodine Reagent.
Authors: Huang Wei‐Jan , Singh Om V. , Chen Chung‐Hsiung , Lee Shoei‐Sheng
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of 2′,3′‐Dideoxy‐2′‐difluoromethyl Azanucleosides.
Authors: Qiu Xiao‐Long , Qing Feng‐Ling
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Novel Spirocyclic Trichothecanes, Spirotenuipesine A and B, Isolated from Entomopathogenic Fungus, Paecilomyces tenuipes.
Authors: Kikuchi Haruhisa , Miyagawa Yasuhiro , Sahashi Yuko , Inatomi Satoshi , Haganuma Asami , Nakahata Norimichi , Oshima Yoshiteru
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Kigamicins, Novel Antitumor Antibiotics. Part 1. Taxonomy, Isolation, Physico‐chemical Properties and Biological Activities.
Authors: Kunimoto Setsuko , Lu Jie , Esumi Hiroyasu , Yamazaki Yohko , Kinoshita Naoko , Honma Yoshiko , Hamada Masa , Ohsono Michiyo , Ishizuka Masaaki , Takeuchi Tomio
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Antagonists of Human CCR5 Receptor Containing 4‐(Pyrazolyl)piperidine Side Chains. Part 2. Discovery of Potent Selective, and Orally Bioavailable Compounds.
Authors: Shen Dong‐Ming , et al. et al.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Carbonic Anhydrase Inhibitors: The First Selective, Membrane‐Impermeant Inhibitors Targeting the Tumor‐Associated Isozyme IX.
Authors: Pastorekova Silvia , Casini Angela , Scozzafava Andrea , Vullo Daniela , Pastorek Jaromir , Supuran Claudiu T.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Hydride Formation, Magnetic and Transport Properties of Nickel and Nickel‐Based Alloys
Authors: Bauer H. J. , Wagner F. E.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
A Short Ride on Scorpionates: from D‐ to F‐Elements
Authors: Paulo Antonio , Correia Joao D. G. , Campello Maria P. C. , Santos Isabel
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Application of Ring‐Closing Metathesis Reactions in the Synthesis of Epothilones
Authors: Rivkin Alexey , Cho Young Shin , Gabarda Ana E. , Yoshimura Fumihiko , Danishefsky Samuel J.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Molecular‐Scale Rotation Movement: Synthesis of Molecular Motors
Authors: Carella Alexandre , Rapenne Gwenael , Launay Jean‐Pierre
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Microwave‐Supported Organic Synthesis: Applications. Part 20.
Authors: Keller Walter E.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Is Combinatorial Chemistry on the Right Track for Drug Discovery?
Authors: Wildonger Richard A. , Deegan Tracy L. , Lee John W.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Silicon, Germanium, Tin and Lead Analogues of Acetylenes
Authors: Power Philip P.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Use of Multicomponent, Domino, and Other One‐pot Syntheses on Solid Phase: Powerful Tools for the Generation of Libraries of Diverse and Complex Compounds
Authors: Pulici M. , Cervi G. , Martina K. , Quartieri F.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
The Medical Geochemistry of Dusts, Soils, and Other Earth Materials
Authors: Plumlee G. S. , Ziegler T. L.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Molecular and Material Design of Biodegradable Poly(hydroxyalkanoate)s
Authors: Abe Hideki , Doi Yoshiharu
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Effective Group Potentials: A Powerful Tool for Hybrid QM/MM Methods?
Authors: Bessac Fabienne , Alary Fabienne , Carissan Yannick , Heully Jean‐Louis , Daudey Jean‐Pierre , Poteau Romuald
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer
Authors: Daling Janet R. , Madeleine Margaret M. , Johnson Lisa Godefroy , Schwartz Stephen M. , Shera Katherine A. , Wurscher Michelle A. , Carter Joseph J. , Porter Peggy L. , Galloway Denise A. , McDougall James K.
Published: June 2004

BACKGROUND

The incidence of anal cancer has increased among both men (160%) and women (78%) from 1973 to 2000 in the U.S. The authors conducted a population‐based case–control study of anal cancer to examine factors that may account for this increase.

METHODS

Men (n = 119 patients) and women (n = 187 patients) who were diagnosed with anal cancer between 1986 and 1998 in the Seattle area were ascertained through the local Surveillance, Epidemiology, and End Results registry. Control participants (n = 1700) were ascertained through random‐digit telephone dialing. Participants were interviewed in person and provided blood samples. Archival tumor tissue was tested for human papilloma virus (HPV) DNA, and serum samples were tested for HPV type 16 (HPV‐16).

RESULTS

Overall, 88% of tumors (all histologies) in the study were found to be positive for HPV. HPV‐16 was the most frequent HPV type detected (73% of all tumors), followed by HPV‐18 (6.9%), regardless of gender. However, 97.7% of tumors from men who were not exclusively heterosexual contained HPV DNA. The risk of anal cancer increased among men (odds ratio [OR], 5.3; 95% confidence interval [95% CI], 2.4–12.0) and women (OR, 11.0; 95% CI, 5.5–22.1) who had ≥ 15 sexual partners during their lifetime. Among men who were not exclusively heterosexual and women, receptive anal intercourse was related strongly to the risk of anal cancer (OR, 6.8 [95% CI, 1.4–33.8] and OR, 2.2 [95% CI, 1.4–3.3], respectively). Current smokers among men and women were at particularly high risk for anal cancer, independent of age and other risk factors (OR, 3.9 [95% CI, 1.9–8.0] and OR, 3.8 [95% CI, 2.4–6.2], respectively).

CONCLUSIONS

The high proportion of tumors with detectable HPV suggests that infection with HPV is a necessary cause of anal cancer, similar to that of cervical cancer. Increases in the prevalence of exposures, such as cigarette smoking, anal intercourse, HPV infection, and the number of lifetime sexual partners, may account for the increasing incidence of anal cancer in men and women. Cancer 2004. © 2004 American Cancer Society.
Pure Organic Phase Phenol Biosensor Based on Tyrosinase Entrapped in a Vapor Deposited Titania Sol‐Gel Membrane
Authors: Yu Jiuhong , Ju Huangxian
Published: June 2004

A novel amperometric biosensor was constructed for the determination of phenols in pure organic phase. This biosensor was fabricated by immobilizing tyrosinase in a titania sol‐gel membrane which was obtained with a vapor deposition method. This method was facile and avoided the calcination step needed in conventional titania sol‐gel process. The titania sol‐gel membrane could effectively retain the essential water layer around the enzyme molecule needed for maintaining its activity in organic phase. The experimental parameters such as solvent and operating potential were optimized. At −100 mV this biosensor showed a good amperometric response to phenols in pure chloroform without any mediator and rehydration of the enzyme. For catechol determination the sensor exhibited a fast response of less than 5 seconds. The sensitivity of different phenols was as follows: catechol > phenol > p‐cresol. Additionally, the apparent Michaelis‐Menten constants of the encapsulated tyrosinase to catechol, phenol and p‐cresol were found to be 0.15±0.003, 0.17±0.008 and 0.21±0.004 mM, respectively. The biosensor had also good reproducibility and stability. This work provided a promising platform for the construction of pure organic phase biosensors and the determination of substrates with poor water solubility.
Gold Electrodes for Detection of Enzyme Assays with 3‐Indoxylphosphate as Substrate
Authors: Castaño‐Álvarez Mario , Fernández‐Abedul M. Teresa , Costa‐García Agustín
Published: June 2004

The advantageous characteristics of gold not only for its electrochemical behavior but also for the unique adsorptive protein characteristics are the basis of this paper. 3‐Indoxyl phosphate (3‐IP) has previously been demonstrated to be a very convenient substrate for the electrochemical detection, using carbon‐based electrodes, of enzymeimmunoassays (EIAs) that employ not only alkaline phosphatase (AP) but also horseradish peroxidase (HRP) as label. Combination of both: gold electrodes and 3‐IP has not been studied and it produces a very suitable detection for EIAs. The electrochemical behavior of indigo, product of the enzymatic hydrolisis of 3‐IP, has been thoroughly studied for the first time on disk and band gold electrodes. The possibility of electrodepositing gold on the bands and automation has also been considered. The detection has been applied for the determination of osteocalcin with an HRP‐based ELISA (enzyme‐linked immunosorbent assay).
Determination of ribavirin in human serum and plasma by capillary electrophoresis
Authors: Breadmore Michael C. , Theurillat Regula , Thormann Wolfgang
Published: June 2004

The electrophoretic separation of ribavirin and 5‐methylcytidine (internal standard) by capillary electrophoresis was examined. Separation was achieved using reverse polarity in a 100 mM borate electrolyte, pH 9.1, with 5 mM spermine added to reduce the electroosmotic flow. Sample preparation based on acetonitrile protein precipitation was found to be unsuitable for ribavirin analysis in patient samples due to insufficient sensitivity and interferences. Solid‐phase extraction employing phenyl boronic acid cartridges provided cleaner separations. Using this approach with 500 μL sample and reconstitution of the dried extract into 100 μL of 33% v/v 100 mM phosphate buffer, pH 6.4 / 67% v/v acetonitrile, the detection and quantitation limits were determined to be 0.05 and 0.10 μg/mL, respectively, a sensitivity that is suitable for therapeutic drug monitoring of ribavirin in human plasma and serum samples. The method was validated and compared to a high‐performance liquid chromatography (HPLC) method, showing excellent agreement between the two for a set of samples that stemmed from patients being treated with ribavirin and interferon‐α‐2b for a hepatitis C virus infection.
Identification of diphenhydramine metabolites in human urine by capillary electrophoresis‐ion trap‐mass spectrometry
Authors: Baldacci Andrea , Prost Francine , Thormann Wolfgang
Published: June 2004

The identification of diphenhydramine (DH) metabolites that are frequently observed in the capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC) analyses of alkaline liquid/liquid and solid‐phase extracts of patient urines is demonstrated. Having standards for DH and diphenhydramine‐N‐oxide (DHNO), the presence of these two compounds could be confirmed in urines that were collected overnight after administration of 25 mg DH chloride. Using CZE coupled to ion‐trap mass spectrometry (CE‐MSn) with positive electrospray ionization and an acetate buffer at pH 5.6, the [M+H]+ ions of DH (m/z = 256), DHNO (m/z = 272), and nordiphenhydramine (NDH, m/z = 242) and their fragmentation to a common m/z 167 product ion (diphenylcarbinol moiety) was monitored. The data indicate that all three compounds are cations in an acidic environment, the migration order being NDH, DH, and DHNO. Data obtained under negative electrospray ionization conditions suggest the presence of diphenylmethoxyacetic acid‐glycine amide ([M‐H]− ion of m/z 298 and fragmentation to m/z 254, loss of CO2), a metabolite that could tentatively be assigned to a characteristic peak observed in the MEKC electropherogram at alkaline pH. The data presented in this paper illustrate the value of using CE‐MSn for identification of urinary drug metabolites for which no standards are available.
Quantitative analysis of DNA methylation in chronic lymphocytic leukemia patients
Authors: Lyko Frank , Stach Dirk , Brenner Axel , Stilgenbauer Stephan , Döhner Hartmut , Wirtz Michaela , Wiessler Manfred , Schmitz Oliver J.
Published: June 2004

Changes in the genomic DNA methylation level have been found to be closely associated with tumorigenesis. In order to analyze the relation of aberrant DNA methylation to clinical and biological risk factors, we have determined the cytosine methylation level of 81 patients diagnosed with chronic lymphocytic leukemia (CLL). The analysis was based on DNA hydrolysis followed by derivatization of the 2'‐desoxyribonucleoside‐3'‐monophosphates with BODIPY FL EDA. Derivatives were separated by micellar electrokinetic chromatography, and laser‐induced fluorescence was used for detection. We analyzed potential correlations between DNA methylation levels and numerous patient parameters, including clinical observations and biological data. As a result, we observed a significant correlation with the immunoglobulin variable heavy chain gene (VH) mutation status. This factor has been repeatedly proposed as a reliable prognostic marker for CLL, which suggests that the methylation level might be a valuable factor in determining the prognostic outcome of CLL. We are now in the process of refining our method to broaden its application potential. In this context, we show here that the oxidation of the fluorescence marker in the samples and the evaporation of methanol in the electrolytes can be prevented by a film of paraffin oil. In summary, our results thus establish capillary electrophoresis as a valuable tool for analyzing the DNA methylation status of clinical samples.
Selection of migration parameters for a highly reliable assignment of bands of isoforms of erythropoietin separated by capillary electrophoresis
Authors: Lacunza Izaskun , Lara‐Quintanar Pilar , Moya Galina , Sanz Jesus , Diez‐Masa Jose C. , de Frutos Mercedes
Published: June 2004

Capillary zone electrophoresis of samples of recombinant human erythropoietin is performed. An in‐house computer program is developed to compare the reliability of different migration parameters to assign the close migration bands of isoforms of erythropoietin. The migration time relative to the electroosmotic flow marker and the effective electrophoretic mobility are selected as the most accurate parameters. Percentages of correct assignment of bands higher than 99% are obtained with these parameters even when changes in operational factors are introduced. The chosen parameters have been applied to assign bands of isoforms in commercial samples of α‐ and β‐epoetin. The same capillary electrophoresis method has been applied to separate bands of isoforms of an erythropoietin analogue, darbepoetin α, the novel erythropoiesis‐stimulating protein.
Determination of nonsteroidal anti‐inflammatory drugs in human specimens by capillary zone electrophoresis and micellar electrokinetic chromatography
Authors: Makino Kazutaka , Itoh Yoshinori , Teshima Daisuke , Oishi Ryozo
Published: June 2004

Therapeutic drug monitoring of anti‐inflammatory drugs is necessary for the identification of the agents that cause toxic events and for the decision on the treatment for intoxication. Recently, capillary electrophoresis (CE) has been developed for the simple and rapid analyses of a variety of chemical agents. Micellar electrokinetic chromatography (MEKC) can separate acidic, neutral and basic anti‐inflammatory drugs in serum. Furthermore, serum samples are directly applied to the CE system without any pretreatments, and some anti‐inflammatory drugs can be separated from serum albumin in the MEKC analysis. On the other hand, capillary zone electrophoresis (CZE) enables us to determine a few μg/mL levels of acidic anti‐inflammatory drugs with simple running buffer and stacking technique. A rapid and simultaneous determination of several analgesic anti‐inflammatory agents, including ibuprofen, acetaminophen, indomethacin, and salicylic acid in human serum has been developed by using CZE. Therefore, the CZE and MEKC analysis may become a potentially useful alternative to high‐performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA) for therapeutic drug monitoring, particularly in serum of patients suffering from intoxication by overdosage of nonsteroidal anti‐inflammatory agents.
Isotachophoresis of β‐blockers in a capillary and on a poly(methyl methacrylate) chip
Authors: Kriikku Pirkko , Graß Benedikt , Hokkanen Ari , Stuns Ingmar , Sirén Heli
Published: June 2004

Analysis of the β‐blockers oxprenolol, atenolol, timolol, propranolol, metoprolol, and acebutolol in human urine by a combination of isotachophoresis (ITP) and zone electrophoresis (ZE) was investigated. Methods were developed with a conventional capillary electrophoresis (CE) apparatus and a poly(methyl methacrylate) (PMMA) microchip system. With CE the separation of oxprenolol, atenolol, timolol, and acebutolol from a standard solution containing 5 μg/mL of each compound was accomplished by performing ZE with transient ITP. The electrolyte system consisted of 10 mM sodium morpholinoethane sulfonate (pH 5.5) and 0.1% methylhydroxyethylcellulose as the leading electrolyte and 30 mM ortho‐phosphoric acid (pH 2.0) as both the terminating and the ZE background electrolyte. With the microchip system the separation of oxprenolol and acebutolol from a standard solution containing 10 μg/mL of each compound was accomplished by a coupled‐channel ITP‐ZE device using the same leading electrolyte solution as the CE system but 5 mM glutamic acid (pH 3.4) as terminating and background electrolytes. The systems were used for analyses of patient urine samples. Water‐soluble hydrophilic matrix compounds were removed from the urine samples by solid‐phase extraction (SPE). Limits of quantification below 5 μg/mL could be achieved. The PMMA ITP‐ZE chip has not earlier been used for analyses of any drugs from urine samples.
Rapid analysis of inflammatory cytokines in cerebrospinal fluid using chip‐based immunoaffinity electrophoresis
Authors: Phillips Terry M.
Published: June 2004

A chip‐based capillary electrophoresis system has been designed for rapidly measuring the concentrations of inflammatory cytokines in the cerebrospinal fluid of patients with head trauma. Isolation of the reactive cytokines was achieved by immunoaffinity capture using a panel of six immobilized antibodies, directly attached to the injection port of the chip. The captured cytokines were labeled in situ with a red light‐emitting laser dye and electroeluted into the separation channel. Separation of the isolated cytokines was achieved by electrophoresis in under 2 min with quantification of the resolved peaks being achieved by on‐line laser‐induced fluorescence and integration of each peak area. Comparison of the results to commercially available high‐sensitivity immunoassays demonstrates that the chip‐based assay provides a fast, accurate procedure for studying the concentrations of these analytes in complex biological materials. The degree of accuracy and precision achieved by the chip‐based CE is comparable to conventional immunoassays, the system being able to analyze between 10–12 samples per hour. With the ever‐expanding array of antibodies that are commercially available, this chip‐based system can be applied to a wide variety of different analyses.
A high‐performance multilane microdevice system designed for the DNA forensics laboratory
Authors: Goedecke Nils , McKenna Brian , El‐Difrawy Sameh , Carey Loucinda , Matsudaira Paul , Ehrlich Daniel
Published: June 2004

We report preliminary testing of “GeneTrack”, an instrument designed for the specific application of multiplexed short tandem repeat (STR) DNA analysis. The system supports a glass microdevice with 16 lanes of 20 cm effective length and double‐T cross injectors. A high‐speed galvanometer‐scanned four‐color detector was specially designed to accommodate the high elution rates on the microdevice. All aspects of the system were carefully matched to practical crime lab requirements for rapid reproducible analysis of crime‐scene DNA evidence in conjunction with the United States DNA database (CODIS). Statistically significant studies demonstrate that an absolute, three‐sigma, peak accuracy of 0.4–0.9 base pair (bp) can be achieved for the CODIS 13‐locus multiplex, utilizing a single channel per sample. Only 0.5 μL of PCR product is needed per lane, a significant reduction in the consumption of costly chemicals in comparison to commercial capillary machines. The instrument is also designed to address problems in temperature‐dependent decalibration and environmental sensitivity, which are weaknesses of the commercial capillary machines for the forensics application.
Quality control and quality assurance aspects of the routine use of capillary electrophoresis for serum and urine proteins in clinical laboratories
Authors: Jenkins Margaret A.
Published: June 2004

Using capillary electrophoresis (CE) for serum protein electrophoresis, the quality of results begins with monitoring a well‐functioning instrument, using scrupulously clean capillaries, well‐calibrated methods as well as regular use of an internal quality control material. Quality assurance programs are available in countries such as Australia, United Kingdom, United States, and European countries such as Sweden and Germany. The present commercial control material that is available gives percentages of albumin, alpha 1, alpha 2, beta‐ and gamma‐globulins, the gamma‐component being of normal distribution, and not containing any monoclonal protein component. We feel that a quantitative commercial control material containing a monoclonal protein at decision level for treating myeloma patients would be beneficial to all laboratories as a serum protein electrophoresis control, whether the analysis is by CE or agarose gels. The same applies for control material for urinary protein electrophoresis.
Recent developments in the determination of urinary cancer biomarkers by capillary electrophoresis
Authors: Ma Yinfa , Liu Guanshu , Du Ming , Stayton Isaac
Published: June 2004

Investigation of effective biomarkers for cancers is currently a popular area of study in clinical and cancer researches, because it can potentially lead to pre‐cancer screening or pre‐cancer diagnosis and may provide useful information on cancer type and the disease's stage of progression. More and more biochemical or chemical fluid components of the human body such as urine, blood, and cerebrospinal fluid have been considered to contain biomarkers, which are useful in cancer researches, pre‐cancer diagnosis, and cancer follow‐ups during or after cancer treatment. Several modern analytical techniques, such as gas chromatography (GC), high‐performance liquid chromatography (HPLC), capillary electrophoresis (CE), and other separation techniques as well as hyphenated techniques, have been extensively used in study of cancer biomarkers. Among these techniques, CE is considered to be a highly efficient and practical analytical technique because of the small sample volume requirement and its wide separation versatility, ranging from small inorganic molecules to large biomolecules. This review discusses the latest developments involving biomarkers and their analysis by CE, including a discussion of instrumental conditions, method developments, and data analysis.
Rapid analysis of antimicrobial metabolites monoacetylphloroglucinol and 2,4‐diacetylphloroglucinol using capillary zone electrophoresis
Authors: Guihen Elizabeth , Glennon Jeremy D. , Cullinane Meabh , O'Gara Fergal
Published: June 2004

A rapid capillary electrophoretic (CE) method was developed for the determination of phloroglucinol compounds, monoacetylphloroglucinol (MAPG) and 2,4‐diacetylphloroglucinol (DAPG), in microbial supernatants of Pseudomonas fluorescens F113 over a 24‐h growth cycle. Prior to electrophoretic separation, solid‐phase extraction of supernatant samples on octadecylsilica for the purpose of sample cleanup is recommended. The optimum electrophoretic conditions were found to be 25 mM sodium tetraborate running buffer at pH 9.3, temperature at 25°C with an applied voltage of 25 kV. The capillary was an Agilent fused‐silica capillary of total length 33 cm×50 μm inner diameter, 375 μm outer diameter, with effective length 24.5 cm. While MAPG and DAPG were monitored at selected wavelengths in the range of 214–320 nm, analysis at 214 nm was used and a CE separation time of less than 2 min was achieved. A partial method validation study was performed in accordance with European Agency for Evaluation of Medicinal Products (EMEA) guidelines. The method displayed linearity over the investigated range of 10–200 μg/mL, with limits of detection of 1.2 μg/mL for MAPG and 1.3 μg/mL for DAPG.
Production of Phenolics from Corn Cobs by Coupling Enzymic Treatment and Solid State Fermentation
Authors: Topakas E. , Kalogeris E. , Kekos D. , Macris B.J. , Christakopoulos P.
Published: June 2004

Corn cobs are important by‐products of the sweet corn processing industry. A large quantity of corn cobs thus generated remains unused as cellulosic wastes in fields and factories or used as animal feed. As in the field of other agro‐industrial plant cell‐wall waste materials, academic and industrial researchers are putting more and more effort into obtaining high‐value compounds from this waste, which can be converted into novel consumer goods by the industries involved.
Removal of Heavy Metals from the Environment by Biosorption
Authors: Gavrilescu M.
Published: June 2004

The pollution of the environment with toxic metals is a result of many human activities, such as mining and metallurgy, and the effects of these metals on the ecosystems are of large economic and public‐healthsignificance. This paper presents the features and advantages of the unconventional removal method of heavy metals – biosorption – as a part of bioremediation. Bioremediation consists of a group of applications, which involvethe detoxification of hazardous substances instead of transferring them from one medium to another, by means of microbes and plants. This process is characterized as less disruptive and can be often carried out on site, eliminating the need to transport the toxic materials to treatment sites. The biosorption (sorption of metallic ions from solutions by live or dried biomass) offers an alternative to the remediation of industrial effluents as well as the recovery of metals contained in other media. Biosorbents are prepared from naturally abundant and/or waste biomass. Due to the high uptake capacity and very cost‐effective source of the raw material, biosorption is a progression towards a perspective method. The mechanism by which microorganisms take up metals is relatively unclear, but it has been demonstrated that both living and non‐living biomass may be utilized in biosorptive processes, as they often exhibit a marked tolerance towards metals and other adverse conditions. One of their major advantages is the treatment of large volumes of effluents with low concentrations of pollutants. Models developed were presented to determine both the number of adsorption sites required to bind each metal ion and the rate of adsorption, using a batch reactor mass balance and the Langmuir theory of adsorption to surfaces or continuous dynamic systems. Two main categories of bioreactors used in bioremediation – suspended growth and fixed film bioreactors – are discussed. Reactors with varying configurations to meet the different requirements for biosorption are analyzed considering two major groups of reactors –batchreactors andcontinuousreactors. Biosorption is treated as an emerging technology effective in removing even very low levels of heavy metal.
Study of Extracellular Plant Lactase
Authors: Neubert K. , Stano J. , Mičieta K. , Koreňová M. , Blanáriková V.
Published: June 2004

Using a synthetic substrate, a simple and sensitive procedure for the determination of extracellular lactase was developed. The enzyme studied produced by the tested plant material hydrolyzed the substrate (1‐naphtyl‐α‐D‐galactopyranoside) to α‐D‐galactose and 1‐naphthol. By simultaneous azocoupling of 1‐naphthol hardly water‐soluble azo‐dyes were produced. The evaluation of the intensity of dyed zones allowed the extracellular lactase activity to be assessed. The agar plate method described permitted rapid, simple, and specific detection of plant producers of extracellular lactase and proved to be perspectively useful in inhibitory and/or biotechnological studies.
The role of consumer knowledge of insurance benefits in the demand for preventive health care among the elderly
Authors: Parente Stephen T. , Salkever David S. , DaVanzo Joan
Published: June 2004

In 1992, the United States Centers for Medicare and Medicaid Services (CMS) introduced new insurance coverage for two preventive services – influenza vaccinations and mammograms. Economists typically assume transactions occur with perfect information and foresight. As a test of the value of information, we estimate the effect of consumer knowledge of these benefits on their demand. Treating knowledge as endogenous in a two‐part model of demand, we find that consumer knowledge has a substantial positive effect on the use of preventive services. Our findings suggest that strategies to educate the insured Medicare population about coverage of preventive services may have substantial social value. Copyright © 2004 John Wiley & Sons, Ltd.
Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome
Authors: Wong Florence , Pantea Lavinia , Sniderman Kenneth
Published: June 2004

Hepatorenal syndrome (HRS) is a functional renal disorder complicating decompensated cirrhosis. Treatments to date, except liver transplantation, have been able to improve but not normalize renal function. The aim of this study was to determine the efficacy of transjugular intrahepatic portosystemic stent shunt (TIPS) as a treatment for type 1 HRS in ascitic cirrhotic patients, following improvement in systemic hemodynamics with a combination of midodrine, octreotide, and albumin (medical treatment). Fourteen ascitic cirrhotic patients with type 1 HRS received medical therapy until their serum creatinine reached below 135 μmol/L for at least 3 days, followed by a TIPS if there were no contraindications. Patients were assessed before and after medical treatment, as well as at 1 week and 1, 3, 6, and 12 months post-TIPS with measurements of renal function, sodium handling, systemic hemodynamics, central blood volume, and hormonal markers. Medical therapy for 14 ± 3 days improved renal function (serum creatinine: 233 ± 29 μmol/L vs. 112 ± 8 μmol/L, P = .001) and renal sodium excretion (5 ± 2 mmol/d vs. 9 ± 2 mmol/d, P = .002) in 10 of the 14 patients. TIPS insertion in five of the responders further improved renal function and sodium excretion, so that by 12 months post-TIPS, glomerular filtration rate (96 ± 20 mL/min, P < .01 vs. pre-TIPS) and urinary sodium excretion (119 ± 15 mmol/d, P < .01 vs. pre-TIPS) were normal, associated with normalization of plasma renin and aldosterone levels and elimination of ascites. In conclusion, TIPS is an effective treatment for type 1 HRS in suitable patients with cirrhosis and ascites, following the improvement of renal function with combination therapy of midodrine, octreotide, and albumin. (Hepatology 2004;40:55-64.)
Linking workplace literacy skills and transfer system perceptions
Authors: Bates Reid , Holton III Elwood F.
Published: June 2004

Research examining the relationship between workplace literacy and training‐related factors is virtually nonexistent. This study examined how variations in individual learning transfer system perceptions were associated with job‐related workplace literacy skill differences. Results indicated significant differences in learning transfer system perceptions for employees who had the math and reading skill levels required for their jobs versus those who did not. Findings suggest a complex and little understood relationship between workplace literacy skills and learning transfer system perceptions.
Analysis of gene expression profiles in human HL‐60 cell exposed to cantharidin using cDNA microarray
Authors: Zhang Jun‐Ping , Ying Kang , Xiao Zhen‐Yu , Zhou Bin , Huang Qing‐Shan , Wu Hong‐Mei , Yin Ming , Xie Yi , Mao Yu‐Min , Rui Yao‐Cheng
Published: June 2004

Cantharidin is a natural toxin that has antitumor properties and causes leukocytosis as well as increasing sensitivity of tumor cells resistant to other chemotherapeutic agents. There is limited information, however, on the molecular pharmacological mechanisms of cantharidin on human cancer cells. We have used cDNA microarrays to identify gene expression changes in HL‐60 promyeloid leukemia cells exposed to cantharidin. Cantharidin‐treated cells not only decreased expression of genes coding for proteins involved in DNA replication (e.g., DNA polymerase delta), DNA repair (e.g., FANCG, ERCC), energy metabolism (e.g., isocitrate dehydrogenase alpha, ADP/ATP translocase), but also decreased expression of genes coding for proteins that have oncogenic activity (e.g., c‐myc, GTPase) or show tumor‐specific expression (e.g., phosphatidylinositol 3‐kinase). In contrast, these treated cells overexpressed several genes that encode intracellular and secreted growth‐inhibitory proteins (e.g., BTG2, MCP‐3) as well as proapoptotic genes (e.g., ATL‐derived PMA‐responsive peptide). Our findings suggest that alterations in specific genes functionally related to cell proliferation or apoptosis may be responsible for cantharidin‐mediated cytotoxicity. We also found that exposure of HL‐60 cells to cantharidin resulted in the decreased expression of multidrug resistance‐associated protein genes (e.g., ABCA3, MOAT‐B), suggesting that cantharidin may be used as an oncotherapy sensitizer, and the increased expression of genes in modulating cytokine production and inflammatory response (e.g., NFIL‐3, N‐formylpeptide receptor), which may partly explain the stimulating effects on leukocytosis. Our data provide new insight into the molecular mechanisms of cantharidin. © 2003 Wiley‐Liss, Inc.
β‐Catenin activates a coordinated expression of the proinvasive factors laminin‐5 γ2 chain and MT1‐MMP in colorectal carcinomas
Authors: Hlubek Falk , Spaderna Simone , Jung Andreas , Kirchner Thomas , Brabletz Thomas
Published: June 2004

In colorectal carcinomas, loss‐of‐function mutations of the adenomatous polyposis coli (APC) tumor suppressor gene lead to a nuclear accumulation of the oncogenic transcriptional activator β‐catenin, predominantly at the invasive front within the tumor host interface. Various identified genes activated by β‐catenin are associated with tumor invasion. One prerequisite for malignant tumor invasion is the ability of tumor cells to migrate. We recently described the γ2 chain of laminin as another β‐catenin target gene. Fragments of the laminin γ2 chain, resulting from cleavage by the membrane type 1 matrix metalloproteinase (MT1‐MMP), are strong inducers of epithelial cell migration. We here show a coordinated expression of nuclear β‐catenin, its target gene and MT1‐MMP substrate laminin γ2 chain, as well as MT1‐MMP in tumor cells at invasive regions of colorectal carcinomas. We further demonstrate that MT1‐MMP expression is regulated by β‐catenin/TCF through a TCF binding site in its promoter. These results suggest that nuclear β‐catenin activates the coordinated expression of the interacting proinvasive proteins laminin γ2 chain and MT1‐MMP, thereby leading to a promigratory activity at the invasive front of colorectal cancers. This further supports an important role of β‐catenin for invasion and metastasis of colorectal carcinomas. © 2003 Wiley‐Liss, Inc.
The fibroblast: Sentinel cell and local immune modulator in tumor tissue
Authors: Silzle Tobias , Randolph Gwendalyn J. , Kreutz Marina , Kunz‐Schughart Leoni A.
Published: June 2004

Development and progression of epithelial malignancies are frequently accompanied by complex phenotypic alterations of resident tissue fibroblasts. Some of these changes, such as myofibroblastic differentiation and an oncofetal extracellular matrix (ECM) expression profile, are also implicated in inflammation and tissue repair. Studies over the past decade revealed the relevance of reciprocal interactions between tumor cells and tumor‐associated host fibroblasts (TAF) in the malignant process. In many tumors, a considerable fraction of the inflammatory infiltrate is located within the fibroblast‐ and ECM‐rich stromal compartment. However, while fibroblasts are known as “sentinel cells” in various nonneoplastic diseases, where they often regulate the composition and function of recruited leucocytes, they are hardly considered active participants in the inflammatory host response in tumors. This article focuses on the functional impact of TAF on immune cells. The complex network of immune‐modulating effects transduced by TAF and TAF‐derived factors is highlighted, and recent reports that support the hypothesis that TAF are involved in the inflammatory response and immune suppression in tumors are reviewed. The role of TAF‐dependent ECM remodeling and TAF‐derived peptide growth factors, cytokines, and chemokines in the immune modulation is stressed and the idea of TAF as an important therapeutic target is emphasized. © 2003 Wiley‐Liss, Inc.
Synergy between anti‐endoglin (CD105) monoclonal antibodies and TGF‐β in suppression of growth of human endothelial cells
Authors: She Xinwei , Matsuno Fumihiko , Harada Naoko , Tsai Hilda , Seon Ben K.
Published: June 2004

Endoglin (CD105) is a proliferation‐associated cell membrane antigen of endothelial cells and strongly expressed in the angiogenic vasculature of solid tumors. Endoglin is essential for angiogenesis/vascular development and an ancillary transforming growth factor β (TGF‐β) receptor. Certain anti‐endoglin monoclonal antibodies (mAbs), termed SN6 series mAbs, inhibited angiogenesis, tumor growth and metastasis in mice. We investigated the mechanisms by which anti‐endoglin mAbs suppress growth of proliferating endothelial cells. We found that 4 SN6 series mAbs suppressed growth of human umbilical vein endothelial cells (HUVECs) in a dose‐dependent manner in the absence of any effector cells or complement. Significant differences in the growth suppression between the 4 anti‐endoglin mAbs defining different epitopes were observed. These differences were not determined by antigen‐binding avidities of the mAbs. Combination of TGF‐β1 and each of the 4 anti‐endoglin mAbs exerted synergistic growth suppression of HUVECs. Binding of anti‐endoglin mAbs to endoglin‐expressing cells did not block the subsequent binding of TGF‐β1. Conversely, preincubation of HUVECs with TGF‐β1 did not change cell surface expression of endoglin. The present results suggest that direct suppression of the endothelial cell growth by SN6 series mAbs is one of the underlying mechanisms by which anti‐endoglin mAbs exert antiangiogenic and tumor‐suppressive activity in vivo. The results further suggest that TGF‐β1 plays an important role in the in vivo antiangiogenic efficacy of anti‐endoglin mAbs by synergistically enhancing the activity of these mAbs. Further studies of the present novel findings may provide valuable information about the functional roles of endoglin and anti‐endoglin mAbs in the TGF‐β‐mediated cell regulation. © 2003 Wiley‐Liss, Inc.
High α‐fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: Significance of hepatitis virus infection, age, p53 and β‐catenin mutations
Authors: Peng Shian‐Yang , Chen Wei J. , Lai Po‐Lin , Jeng Yun‐Ming , Sheu Jin‐Chuan , Hsu Hey‐Chi
Published: June 2004

α‐Fetoprotein (AFP) is often elevated in hepatocellular carcinoma (HCC). This study was to elucidate the significance and related factors of AFP elevation in HCC in 781 unifocal HCCs receiving curative hepatectomy. We showed that high AFP (> 200 ng/ml), which was associated with AFP mRNA expression in HCC (p = 0.00001), correlated with major clinicopathologic factors. Younger age (≤ 55 years; p = 0.00001), hepatitis B surface antigen (HBsAg) in serum (p = 0.00001), p53 mutation (p = 0.008), large tumor (p = 0.00001), vascular invasion (p = 0.00001) and early tumor recurrence (p = 0.00001) were significant associates of high AFP, while anti‐HCV in serum and β‐catenin mutation in HCC had less frequent high AFP (p = 0.013 and < 0.0001, respectively). We also showed that HCC with high AFP had a lower 10‐year survival (p < 0.0001), particularly in large HCC (p < 0.0001). At univariate analysis, high AFP (p < 0.0001), HBsAg positivity (p = 0.05), p53 mutation (p = 0.0004), liver cirrhosis (p = 0.0094), large tumor (p = 0.0003), vascular invasion (p < 0.0001) and early recurrence (p < 0.0001) were significant unfavorable prognostic factors. In Cox proportional hazards regression analysis, high AFP remained a borderline significance (OR = 1.2; CI = 1.0–1.4) after adjustment for the effect of tumor size and tumor stage (p = 0.0821). Furthermore, the detection of AFP mRNA in the liver of AFP mRNA‐positive HCC was associated with more frequent early recurrence (p = 0.0026) and might be a useful marker of intrahepatic spread. We therefore conclude that AFP elevation, more than a coincidental epiphenomenon, appears to contribute to vascular invasion and HCC progression and help to identify subsets of HCC patients with increased risk for early recurrence and poor prognosis after hepatectomy. © 2004 Wiley‐Liss, Inc.
Detection of cancer‐related gene expression profiles in severe cervical neoplasia
Authors: Sopov Igor , Sörensen Till , Magbagbeolu Mandy , Jansen Lars , Beer Katrin , Kühne‐Heid Rosemarie , Kirchmayr Richard , Schneider Achim , Dürst Matthias
Published: June 2004

The molecular signatures of 20 severe cervical intraepithelial neoplasia (CIN3) cases and 10 cervical squamous cell cancers were determined to define cancer‐related gene expression profiles. RNAs extracted from microdissected tissues were amplified by SMART technology and used as probes for hybridization of commercially available cDNA array filters comprising 1,176 cancer‐related genes. Ninety‐two differentially expressed genes were identified by comparison of pooled cDNA from CIN3 vs. cervical cancer. Heterogeneity in expression of this subset of genes was then analyzed for each biopsy using an algorithm for self‐organizing maps. For several gene clusters, the expression pattern for CIN3 differed significantly from that of cancer. Moreover, hierarchical clustering revealed significant differences in distribution of CIN and cancer. Several CIN cases were more strongly related to cancer, suggesting that gene expression profiling may be useful for subdividing pathologically indistinguishable precancers into different biologic entities. This approach also provides a basis for the identification of putative prognostic markers and for targeted molecular therapy. © 2004 Wiley‐Liss, Inc.
Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)
Authors: Cirée Arnaud , Michel Laurence , Camilleri‐Bröet Sophie , Jean Louis Francette , Oster Michèle , Flageul Beatrice , Senet Patricia , Fossiez Francois , Fridman Wolf H. , Bachelez Hervé , Tartour Eric
Published: June 2004

Interleukin‐17 (IL‐17) is a proinflammatory cytokine mainly produced by activated CD4+ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL‐17 may act as a tumor growth‐promoting or ‐inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL‐17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T‐cell lymphomas were selected because they are usually CD3+ CD4+ CD45RO+, a phenotype similar to nontransformed T cells producing IL‐17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL‐17 mRNA and secrete this cytokine. However, IL‐17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL‐17 mRNA, while this cytokine was not detected in normal skin. IL‐17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL‐17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL‐17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte‐released IL‐8. This study is the first report demonstrating that some human tumor cells could express IL‐17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth. © 2004 Wiley‐Liss, Inc.
Hydroxyapatite and fluor‐hydroxyapatite layered film on titanium processed by a sol–gel route for hard‐tissue implants
Authors: Kim Hae‐Won , Knowles Jonathan C. , Salih Vehid , Kim Hyoun‐Ee
Published: June 2004

A double‐layered coating, consisting of a hydroxyapatite (HA) outer film and a fluor‐hydroxyapatite (FHA) inner film, was produced on a Ti substrate by a sol–gel route to improve the biocompatibility and functionality of the system. Dissolution behavior of and in vitro cellular responses to the layered film were investigated. Calcium nitrate and triethyl phosphite were used for calcium and phosphate precursors, respectively, and ammonium fluoride was added as a fluorine‐ion source for FHA. The FHA layer was deposited on Ti by spin coating and subsequent heat treatment at 550°C for 30 min in air, and then the HA layer was laid down over the FHA‐coated Ti under the same conditions. After heat treatment, characteristic apatite structures and phases were developed on both FHA and HA films. The cross‐section view of the HA/FHA film clearly showed a double‐layered structure on Ti with each layer approximately 0.6–0.8‐μm thickness. The coating layer was highly uniform and dense, and adhered to Ti substrate strongly with an adhesion strength of about 40 MPa. The in vitro solubility of the HA/FHA layered film in a physiological solution was between that of HA and FHA pure film, and the dissolution profile was quite biphasic, that is, an initial rapid period and a slowdown with increasing time, reflecting the gradient solubility of the fast HA outer structure/slow FHA inner structure. The human osteoblast‐like HOS TE85 cells cultured on the HA/FHA layered film attached, spread, and grew favorably. The proliferation rate of the cells on the layered film was significantly higher (considered at p < 0.05 for n = 6) than that on Ti substrate and was similar to that on pure HA film. The alkaline phosphatase (ALP) activity and osteocalcin (OC) produced by the cells on the layered film were significantly higher (considered at p < 0.05 for n = 6) than those on Ti substrate. Moreover, the ALP and OC levels of cells on the layered film showed the trends of HA outer/FHA inner structure with respect to culture period, that is, HA initially and FHA later. These observations suggest that the HA/FHA layered film on Ti obtained by a sol–gel route possesses gradient functionality in terms of solubility and cellular responses, and find that those parameters can be tailored for specific use in hard‐tissue implants. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 71B: 66–76, 2004