bluuebunny/crossref_metadata_2025 huggingface dataset:
Shedding light on sheddases: role in growth and development
Authors: Kheradmand Farrah , Werb Zena
Published: August 2002

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

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

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

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

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

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

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

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

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

The recombinant Escherichia coli strain, equipped with the newly cloned Aeromonas PHA biosynthesis genes, could produce a terpolymer of 3‐hydroxybutyrate (3HB), 3‐hydroxyvalerate (3HV), and 3‐hydroxyhexanoate (3HHx) [P(3HB‐co‐3HV‐co‐3HHx)] from dodecanoic acid plus odd carbon number fatty acid. In addition, the orf1 gene of Aeromonas hydrophila was found to play a critical role in assimilating the 3HV monomer and in regulating the monomer fraction in the terpolymer. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 81–86, 2001.
A two‐step enzymatic resolution process for large‐scale production of (S)‐ and (R)‐ethyl‐3‐hydroxybutyrate
Authors: Fishman Ayelet , Eroshov Michael , Sheffer Dee‐Noor Shani , van Mil Jan , Cogan Uri , Effenberger Reinhard
Published: August 2002

An efficient two‐step enzymatic process for production of (R)‐ and (S)‐ethyl‐3‐hydroxybutyrate (HEB), two important chiral intermediates for the pharmaceutical market, was developed and scaled‐up to a multikilogram scale. Both enantiomers were obtained at 99% chemical purity and over 96% enantiomeric excess, with a total process yield of 73%. The first reaction involved a solvent‐free acetylation of racemic HEB with vinylacetate for the production of (S)‐HEB. In the second reaction, (R)‐enriched ethyl‐3‐acetoxybutyrate (AEB) was subjected to alcoholysis with ethanol to derive optically pure (R)‐HEB. Immobilized Candida antarctica lipase B (CALB) was employed in both stages, with high productivity and selectivity. The type of butyric acid ester influenced the enantioselectivity of the enzyme. Thus, extending the ester alkyl chain from ethyl to octyl resulted in a decrease in enantiomeric excess, whereas using bulky groups such as benzyl or t‐butyl, improved the enantioselectivity of the enzyme. A stirred reactor was found unsuitable for large‐scale production due to attrition of the enzyme particles and, therefore, a batchwise loop reactor system was used for bench‐scale production. The immobilized enzyme was confined to a column and the reactants were circulated through the enzyme bed until the targeted conversion was reached. The desired products were separated from the reaction mixture in each of the two stages by fractional distillation. The main features of the process are the exclusion of solvent (thus ensuring high process throughput), and the use of the same enzyme for both the acetylation and the alcoholysis steps. Kilogram quantities of (S)‐HEB and (R)‐HEB were effectively prepared using this unit, which can be easily scaled‐up to produce industrial quantities. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 256–263, 2001.
Economic comparison between conventional and disposables‐based technology for the production of biopharmaceuticals
Authors: Novais J. L. , Titchener‐Hooker N. J. , Hoare M.
Published: August 2002

Time to market, cost effectiveness, and flexibility are key issues in today's biopharmaceutical market. Bioprocessing plants based on fully disposable, presterilized, and prevalidated components appear as an attractive alternative to conventional stainless steel plants, potentially allowing for shorter implementation times, smaller initial investments, and increased flexibility.

To evaluate the economic case of such an alternative it was necessary to develop an appropriate costing model which allows an economic comparison between conventional and disposables‐based engineering to be made. The production of an antibody fragment from an E. coli fermentation was used to provide a case study for both routes. The conventional bioprocessing option was costed through available models, which were then modified to account for the intrinsic differences observed in a disposables‐based option. The outcome of the analysis indicates that the capital investment required for a disposables‐based option is substantially reduced at less than 60% of that for a conventional option. The disposables‐based running costs were evaluated as being 70% higher than those of the conventional equivalent. Despite this higher value, the net present value (NPV) of the disposables‐based plant is positive and within 25% of that for the conventional plant.

Sensitivity analysis performed on key variables indicated the robustness of the economic analysis presented. In particular a 9‐month reduction in time to market arising from the adoption of a disposables‐based approach, results in a NPV which is identical to that of the conventional option. Finally, the effect of any possible loss in yield resulting from the use of disposables was also examined. This had only a limited impact on the NPV: for example, a 50% lower yield in the disposable chromatography step results in a 10% reduction of the disposable NPV. The results provide the necessary framework for the economic comparison of disposables and conventional bioprocessing technologies. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 143–153, 2001.
Analysis of tofisopam in human serum by column‐switching semi‐micro high‐performance liquid chromatography and evaluation of tofisopam bioequivalency
Authors: Baek Soo Kyoung , Choi Sung Jin , Kim Jeong Soo , Park Eun Jeon , Sohn Dong Hwan , Lee Hee‐Yong , Lee Hye Suk
Published: August 2002

A rapid and sensitive column‐switching semi‐micro HPLC method is described for the direct analysis of tofisopam in human serum. The sample (100 µL) was directly injected onto the precolumn (Capcell Pak MF Ph‐1), where unretained proteins were eluted to waste. Tofisopam was then eluted into an enrichment column using 13% acetonitrile in 50 mM phosphate buffer (pH 7.0) containing 5 mM sodium octanesulfonate and subsequently into the analytical column using 43% acetonitrile in 0.1% phosphoric acid containing 5 mM sodium octanesulfonate. The detection limit (2 ng/mL), good precision (CV ≤ 4.2%) and speed (total analysis time 24 min) of the present method were sufficient for drug monitoring. This method was successfully applied to a bioequivalence test of two commercial tofisopam tablets. Copyright © 2002 John Wiley & Sons, Ltd.
Women in danger: intimate partner violence experienced by women who qualify and do not qualify for a protective order
Authors: Gist Julia Henderson , McFarlane Judith , Malecha Ann , Fredland Nina , Schultz Pamela , Willson Pam
Published: August 2002

Not all women who apply qualify for a civil protective order. This study compares the type and severity of violence reported by women who qualified with that experienced by women who did not qualify. Ninety women seeking a protective order against a male intimate were interviewed. Findings indicated that 28% of women applying for a protective order did not qualify primarily because of cohabitation requirements or childbearing status. Actual and threatened violence was measured with the 46‐item Severity of Violence Against Women Scale. A 17‐item questionnaire measured stalking behavior. Levels of reported violence for the preceding 3 months were measured for the two groups. The symbolic threat behavior only of throwing, smashing, or breaking an object was significantly higher for qualifying women. The physical abuse behavior only of being pushed, shoved, or pulled was significantly higher. None of the stalking behaviors were significantly different. Data are urgently needed that document the barriers to abused women receiving protective orders, the relevancy of qualifying criteria, and the effectiveness of protective orders issued. Copyright © 2001 John Wiley & Sons, Ltd.
Absence of the falx cerebelli in a Chiari II malformation
Authors: Tubbs R. Shane , Dockery Stephen E. , Salter George , Elton Scott , Blount Jeffrey P. , Grabb Paul A. , Oakes W. Jerry
Published: August 2002

After a review of the literature, we found no descriptions of the falx cerebelli in the Chiari II population. Other dural partitions in this group have been well‐described. The aim of our study was to radiologically and at autopsy search for the falx cerebelli in this population. We retrospectively analyzed 50 CTs and 50 MRIs in children with a known Chiari II malformation, searching for either the falx cerebelli or internal occipital crest, the bony attachment for the falx cerebelli; these structures were also investigated in two patients at autopsy. We were unable to observe the falx cerebelli or internal occipital crest on any of the radiologic images or at autopsy. We theorize that a “crowded” posterior cranial fossa in these patients inhibits the development of the falx cerebelli and internal occipital crest. Clin. Anat. 2:193–195, 2002. © 2002 Wiley‐Liss, Inc.
Quantitative morphology of full thickness rotator cuff tears
Authors: Wening Jason D. , Hollis Ronald F. , Hughes Richard E. , Kuhn John E.
Published: August 2002

The occurrence of full thickness rotator cuff tears (RCTs) at time of death, the size and distribution of those tears among the tendons of the rotator cuff, and the anterior to posterior and medial to lateral dimensions of the RCTs were determined. A subset of 57 shoulders from a group of 414 were found to have full thickness rotator cuff tears. The three‐dimensional coordinates of specific bony landmarks and points defining the circumference of the RCT were digitized using a Flock of Birds DC electromagnetic tracking device. Bony landmarks were used to determine the separation between adjacent tendons of the rotator cuff. Points describing the circumference of the RCT were used to calculate the area of the tear. The majority of tears occurred in the supraspinatus tendon alone (25), or in both the supraspinatus and infraspinatus tendons (22). The areas of the RCTs ranged from 0.07 cm2 to 19.17 cm2 with an average of 4.43 cm2. The mean anterior to posterior length was 1.95 cm. The mean medial to lateral length was 1.98 cm. Clin. Anat. 15:18–22, 2002. © 2002 Wiley‐Liss, Inc.
Workload and burnout in nurses
Authors: Greenglass Esther R. , Burke Ronald J. , Fiksenbaum Lisa
Published: August 2002

This paper examines the relationship between workload, burnout and somatization in nurses. The respondents consisted of 1363 nurses employed in hospitals, which were undergoing extensive restructuring. Results of structural equation analyses showed that workload was positively related to emotional exhaustion. Emotional exhaustion led to cynicism and somatization, and cynicism was negatively related to nurses' professional efficacy. Implications of the results for nursing practice are discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Pathways to health, illness and well‐being: from the perspective of power and control
Authors: McCubbin Michael
Published: August 2002

This article introduces the special issue entitled ‘Power, Control and Health’. The five articles in this issue, using qualitative observation and theory‐building, deconstruct individualistic explanations of the roles of power, empowerment, control, self‐efficacy, etc. in producing health and well‐being outcomes, and reconstruct models and pathways to population health and well‐being that are profoundly anchored in the social, economic and political dimensions of human life which create, structure, and reinforce power and powerlessness at individual and collective levels. The theory developed here contributes to the understanding of how population health and well‐being are intimately related to and are consequences of power and powerlessness. This is the first published collection addressing the etiology of population health from the perspective of power and powerlessness; as such it not only advances knowledge about the determinants of population health, but provides a more scientific basis for interventions aimed at ‘empowering’ marginalized persons and classes of persons. The topics dealt with include a deconstruction of self‐efficacy theory and the ‘socialization’ of that concept, a model concerned with work and work stress for pathways to health and illness emphasizing class and gender, reflections on the meaning of empowerment in the prevention of unsafe sex practices, a study of empowerment and recovery in the context of changes in a community mental health system, and a systemic model based on the lifecourse perspective for child wellness and resilience centred around power and control. Those articles are followed by a commentary which stresses the need to ‘depsychologize’ community psychology, noting that even the articles in this special issue retain notable vestiges of reductionism to the individual level. This introduction describes the evolution of the public health field into the ‘population health field’ and the pertinence of a focus on power for understanding pathways to health, illness and well‐being. Copyright © 2001 John Wiley & Sons, Ltd.
Caffeic acid phenethyl ester changes the indices of oxidative stress in serum of rats with renal ischaemia–reperfusion injury
Authors: Özyurt Hüseyin , Irmak M. Kemal , Akyol Ömer , Söğüt Sadik
Published: August 2002

Oxygen‐derived free radicals have been implicated in the pathogenesis of renal injury after ischaemia–reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant properties. To investigate whether treatment with either CAPE or alpha‐tocopherol modifies the levels of the endogenous indices of oxidant stress, we examined their effects on an in vivo model of renal ischaemia–reperfusion injury in rats. CAPE at 10 μmol kg−1 or alpha‐tocopherol at 10 mg kg−1 was administered intraperitoneally before reperfusion. Acute administration of both CAPE and alpha‐tocopherol altered the indices of oxidative stress differently in renal ischaemia–reperfusion injury. Copyright © 2001 John Wiley & Sons, Ltd.
Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder
Authors: Kuloglu Murat , Ustundag Bilal , Atmaca Murad , Canatan Halit , Tezcan A. Ertan , Cinkilinc Nadire
Published: August 2002

Recent data from several reports indicate that free radicals are involved in aetiopathogenesis of many human pathologies including neuropsychiatric disorders such as schizophrenia, bipolar disorder etc. In the present study, we aimed at determining and evaluating levels of malondialdehyde (MDA), a product of lipid peroxidation, and antioxidant enzyme superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) activity levels in patients diagnosed with schizophrenia (n = 25) and bipolar disorder (n = 23). The control group was composed of 20 healthy subjects. There was a significant increase in MDA levels of patients with schizophrenia and bipolar disorder compared with controls. SOD and GSH‐Px activity levels were significantly higher in the schizophrenic group compared with controls. SOD activity levels in bipolar the group were significantly higher than controls whereas there were no significant changes in GSH‐Px activity levels in the bipolar group and controls. Significant differences between lipid peroxidation product and antioxidant enzyme (SOD and GSH‐Px) activity levels in schizophrenic and bipolar disorder patients compared with controls leads us to believe that these differences are related to the heterogenities in aetiologies of these disorders. Copyright © 2002 John Wiley & Sons, Ltd.
Cutting balloon angioplasty for children with small‐vessel pulmonary artery stenoses
Authors: Rhodes John F. , Lane Geoffrey K. , Mesia C. Igor , Moore J. Donald , Nasman Colleen M. , Cowan Denise A. , Latson Larry A.
Published: August 2002

Patients with complex congenital heart disease may have pulmonary artery stenoses that are either congenital or associated with scarring following surgical procedures. This study evaluates cutting balloon angioplasty for small‐vessel pulmonary artery stenoses resistant to standard balloon angioplasty. Between October 1998 and December 1999, patients were enrolled in an FDA‐approved compassionate‐use protocol. During four catheterizations, there were seven lesions found resistant to standard balloon angioplasty (mean lesion diameter was unchanged: 1.8 mm ± 0.8 mm to 1.9 ± 0.8 mm). A cutting balloon was inflated twice in each of these lesions. Standard balloon angioplasty was then repeated. Final mean lesion diameter was increased significantly (1.9 mm ± 0.8 mm to 3.8 ± 1.3 mm; P ≤ 0.01). Follow‐up catheterizations performed a median of 14 months later showed only slight decrease in mean lesion diameter (3.2 ± 1.2 mm), still significantly greater than initial mean lesion diameter (P < 0.03). In conclusion, cutting balloon angioplasty for pulmonary artery stenoses resistant to standard balloon angioplasty improves the immediate and intermediate term results of angioplasty for these lesions. Cathet Cardiovasc Intervent 2002;55:73–77. © 2002 Wiley‐Liss, Inc.
Transradial coronary brachytherapy with the Novoste beta‐rail system
Authors: Bertrand Olivier F. , De Larochellière Robert , Gleeton Onil , Plante Sylvain , Tessier Michel , Guimond Jean
Published: August 2002

We report our initial experience in 10 consecutive patients who underwent transradial coronary brachytherapy for in‐stent restenosis using a 90Sr/Y source and the Novoste Beta‐Rail system. In all patients, procedures were successfully completed using a right transradial approach. We performed the procedures with the Beta‐Rail catheter using 7 Fr (Zuma II, Medtronic, MN; n = 5) or 8 Fr (Cordis, Miami, FL; n = 5) guiding catheters. All lesions were successfully dilated and no additional stent was inserted. We used a 40 mm source (n = 3) or a 60 mm source (n = 7) with manual stepping in four cases. In three cases, we did one stepping, and in one case, we did three steppings. The mean dwell time was 195 ± 44 sec. The mean delivered dose was 23 ± 3 Gy at 2 mm distance from the source. No radiation treatment was interrupted. Mean fluoroscopy time was 26 ± 13 min. Procedural success was achieved in all patients. Three patients had mild CK elevations (< 3 times upper normal limit). All patients were pretreated with clopidogrel (300 mg) and combined treatment with aspirin + clopidogrel is to be continued for at least 1 year. Clinical follow‐up up to 3 months has not yielded any complication and all patients have remained free from angina. Cathet Cardiovasc Intervent 2002;55:362–366. © 2002 Wiley‐Liss, Inc.
Comparison of two different methods of quantitative coronary angiography in patients with acute coronary syndromes
Authors: Sheynberg Boris V. , Jang Ik‐Kyung , Han Richard O. , Sabatine Marc S. , Brown David F.M. , Dinsmore Robert
Published: August 2002

The minimal cost algorithm (MCA) commonly used for quantitative coronary arteriography has limitations in definition of complex lesion morphology. A gradient field transform (GFT) algorithm has been designed for the better analysis of complex lesions. We compared MCA with GFT in angiograms of 125 patients in the Myocardial Infarction with Novastan and t‐PA (MINT) trial. Lesion border definition was rated as one (poor), two (good), or three (very good). While MCA‐ and GFT‐derived reference diameters (RDs) were similar, GFT yielded smaller minimal lumen diameter (MLD) than MCA by 0.22 ± 0.31 mm (P < 0.01), and the difference between GFT‐ and MCA‐derived MLDs increased with decreasing MLD. Mean percent diameter stenosis (% DS) was 9.1% ± 11.1% greater by GFT (P < 0.001). Lesion border definition in simple lesions was similar (not significantly different). However, in complex lesions GFT performed better (2.49 ± 0.61 vs. 2.11 ± 0.74; P < 0.05). Thus, GFT appears to improve analysis of complex lesions compared to MCA. GFTs role in angiographic trials and clinical practice deserves further study. Cathet Cardiovasc Intervent 2002;55:442–449. © 2002 Wiley‐Liss, Inc.
In vitro and in vivo comparison of three different intravascular ultrasound catheter designs
Authors: Fort Stephen , Freeman Norman A. , Johnston Paul , Cohen Eric A. , Foster F. Stuart
Published: August 2002

Intravascular ultrasound (IVUS) is an invasive imaging modality, which provides detailed two‐dimensional images of blood vessels. There are currently two different types of IVUS catheters available, namely, the phased‐array and the mechanical designs. The operating ultrasound frequency of these catheters ranges from 20 to 40 MHz. This study sought to evaluate the image quality, accuracy of diameter and pullback length measurements, and catheter handling characteristics of three different IVUS catheters currently available for clinical use using both in vitro phantom models and in patients undergoing percutaneous coronary intervention (PCI). In gelatin phantom models, image quality assessed on a semiquantitative scale was significantly different between the three IVUS catheters (P = 0.01) with the 40‐MHz catheter providing the best images. Accuracy of lumen diameter measurements, when compared to optical microscopy, were similar between the three IVUS catheter designs (all R2 = 0.99). There were no significant differences in accuracy of pullback length measurements in vitro between the three designs. However, there were differences in the performance of the three IVUS catheters when used for preinterventional imaging in patients undergoing PCI. Both mechanical IVUS catheters were associated with lower procedural, fluoroscopy, and lesion crossing times compared to the phased‐array catheter (all P < 0.05). There were no significant differences between the catheters during postinterventional IVUS imaging. There were also small but potentially important differences with regards to clinical events and complications associated with the use of the different IVUS catheters during the PCI procedures, reflecting differences in catheter design. Cathet Cardiovasc Intervent 2001;52:382–392. © 2001 Wiley‐Liss, Inc.
Morphological variations of secundum‐type atrial septal defects: Feasibility for percutaneous closure using Amplatzer septal occluders
Authors: Podnar Tomaž , Martanovič Peter , Gavora Pavol , Masura Jozef
Published: August 2002

The aim of the study was to assess the morphology of secundum‐type atrial septal defects (ASD) with a view to percutaneous closure using Amplatzer septal occluders (ASO). One hundred and ninety patients who underwent closure of isolated secundum‐type ASD between September 1995 and January 2000 were included. The morphology of the defects was studied using transthoracic and transesophageal echocardiography. Patients with defects of suitable morphology and size underwent percutaneous closure using ASO. The remaining patients underwent surgical closure. Centrally placed defects were observed in 46 patients (24.2%). Morphological variations of secundum‐type ASD were detected in 144 patients (75.8%). One hundred and fifty‐one patients (79.5%) underwent percutaneous closure using ASO. Thirty‐nine patients (20.5%) underwent surgical closure. Centrally placed defects, defects with deficient superior anterior rim, multiple defects, and perforated aneurysms of the interatrial septum are morphological variations of secundum‐type ASD suitable for percutaneous closure using ASO. Cathet Cardiovasc Intervent 2001;53:386–391. © 2001 Wiley‐Liss, Inc.
Closure of the fenestration in the extracardiac Fontan with the Amplatzer duct occluder device
Authors: Rueda Fernando , Squitieri Cosimo , Ballerini Luigi
Published: August 2002

We report the successful use of the Amplatzer duct occluder for the delayed closure of the fenestration in three patients who underwent an extracardiac modified Fontan procedure. At the moment of closure, the patients were 5.5, 2.7, and 3 years old (29 months, 3 months, and 14 months after the Fontan procedure, respectively). Immediate full occlusion was achieved in all cases. In addition, arterial saturation increased significantly (> 5%) with no hemodynamic deterioration. There were no complications during or after the procedure, and the patients were discharged in good conditions the day after and with uneventful follow‐up. In conclusion, the Amplatzer duct is safe and effective for the closure of the fenestration in the extracardiac Fontan. Cathet Cardiovasc Intervent 2001;54:88–92. © 2001 Wiley‐Liss, Inc.
Fundamentals of x‐ray imaging and radiation safety
Authors: Bashore Thomas
Published: August 2002

A basic understanding of the means by which images are acquired and processed in the cardiac catheterization laboratory should be a fundamental part of every cardiology training program. This review outlines the entire X‐ray system step‐by‐step by following the flow of energy from the generator to the monitor display. In addition, an overview of the major issues in radiation safety are discussed in simple terms focusing on both occupational and patient exposure, and the ways to minimize radiation dosage. Cathet Cardiovasc Intervent 2001;54:126–135. © 2001 Wiley‐Liss, Inc.
StressDB: A locally installable web‐based relational microarray database designed for small user communities
Authors: Mitra Madhusmita , Shah Nigam , Mueller Lukas , Pin Scuth , Fedoroff Nina
Published: August 2002

We have built a microarray database, StressDB, for management of microarray data from our studies on stress‐modulated genes in Arabidopsis. StressDB provides small user groups with a locally installable web‐based relational microarray database. It has a simple and intuitive architecture and has been designed for cDNA microarray technology users. StressDB uses Windows™ 2000 as the centralized database server with Oracle™ 8i as the relational database management system. It allows users to manage microarray data and data‐related biological information over the Internet using a web browser. The source‐code is currently available on request from the authors and will soon be made freely available for downloading from our website at http://arastressdb.cac.psu.edu. Copyright © 2002 John Wiley & Sons, Ltd.
Seen and heard but how well informed? Children's perceptions of the guardian ad litem service
Authors: Ruegger Maria
Published: August 2002

This paper is an account of a study which explored children's perceptions of the guardian and litem service and their experiences of public law proceedings. Whilst generally children felt positive about the service they received, in areas such as their attendance at court, who had access to the information they gave to their guardians, the arrangements made in regard to expert witnesses and the ability of guardians and the courts to influence care plans, a number of strong themes emerged. These are described and the implications of these findings for guardians and other professionals who practice in the field of family law are considered. Copyright © 2001 John Wiley & Sons, Ltd.
Contractility of single human dermal myofibroblasts and fibroblasts
Authors: Wrobel Louise K. , Fray Tim R. , Molloy Justin E. , Adams Julian J. , Armitage Mark P. , Sparrow John C.
Published: August 2002

Human dermal myofibroblasts, characterised by the expression of α‐smooth muscle actin, are part of the granulation tissue and implicated in the generation of contractile forces during normal wound healing and pathological contractures. We have compared the contractile properties of single human dermal fibroblasts and human dermal myofibroblasts by culturing them on flexible silicone elastomers. The flexibility of the silicone substratum permits the contractile forces exerted by the cells to be measured [Fray et al., 1998: Tissue Eng. 4:273–283], without changing their expression of α‐smooth muscle actin. The mean contractile force produced by myofibroblasts (2.2 μN per cell) was not significantly different from that generated by fibroblasts (2.0 μN per cell) when cultured on a substrata with a low elastomer stiffness. Forces produced by fibroblasts were unaffected by increases in elastomer stiffness, but forces measured for myofibroblasts increased to a mean value of 4.1 μN/cell. This was associated with a higher proportion of myofibroblasts being able to produce wrinkles on elastomers of high stiffness compared to fibroblasts. We discuss the force measurements at the single cell level, for both fibroblast and myofibroblasts, in relation to the proposed role of myofibroblasts in wound healing and pathological contractures. Cell Motil. Cytoskeleton 52:82–90, 2002. © 2002 Wiley‐Liss, Inc.
250 MHz crossed‐loop resonator for pulsed electron paramagnetic resonance
Authors: Rinard George A. , Quine Richard W. , Eaton Gareth R. , Eaton Sandra S.
Published: August 2002

The crossed‐loop resonator (CLR) uses two orthogonal lumped‐element resonators [one to excite the spins and one to detect the electron paramagnetic resonance (EPR)] to isolate the signal from the microwave source. It eliminates the need for a circulator. The high isolation provided by the CLR reduces the energy stored in the resonator that detects the signal, thereby reducing the intensity of the resonator ring down after the pulse, which decreases the instrument dead time. Overcoupling and synchronous switching of the Q's of the two resonators between high and low states were used to further reduce dead time and maximize the EPR signal following a pulse. Each section of a 250 MHz resonator that accommodates 1 inch diameter samples had a critically coupled Q of 950 when Q‐switching was not installed. With Q‐switching, free induction decays and electron spin echoes for 0.2 mM aqueous solutions of triarylmethyl radicals were obtained with dead times of a few hundred nanoseconds. Typically 50–60 dB isolation was achieved with various samples. © 2002 Wiley Periodicals, Inc. Concepts in Magnetic Resonance (Magn Reson Engineering) 15: 37–46, 2002.
Clinical significance of plasma endostatin in acute myeloid leukemia/myelodysplastic syndrome
Authors: Lai Raymond , Estey Elihu , Shen Yu , Despa Simona , Kantarjian Hagop , Beran Miloslav , Maushouri Taghi , Quackenbuch Robert C. , Keating Micheal , Albitar Maher
Published: August 2002

BACKGROUND

Endostatin, a C‐terminal fragment of collagen XVIII, is an endogenous angiogenesis inhibitor. While endostatin is being investigated for its usefulness in treating solid tumors, its significance in hematologic malignancies is unknown.

METHODS

The authors evaluated plasma endostatin (PE) levels using an enzyme linked immunoassay in 71 patients with acute myeloid leukemia (AML) and 43 patients with myelodysplastic syndrome (MDS), and correlated PE with various clinical parameters.

RESULTS

There was no significant difference in the median PE level between AML/MDS patients and the normal controls. Nevertheless, patients who achieved complete remission (CR) had a significantly lower median PE level compared to those who did not. In multivariate analysis, PE was found to be a significant (P = 0.03) predictor of overall survival (OS) with adjustment of the other baseline covariates, including patient age, history of antecedent hematologic disorders, and the use of protective environments. The prognostic value of PE was also evaluated by dividing MDS/AML patients into high and low PE groups using the median PE level of normal controls as the cut‐off. The authors found that patients in the high PE group survived for a significantly shorter time than those patients in the low PE group.

CONCLUSIONS

PE is a useful prognostic predictor of CR and OS for AML/MDS patients. The mechanism underlying the association between high PE and poor clinical outcome is unclear, although it may be related to the possible PE reflection of tumor burden. Cancer 2002;94:14–7. © 2002 American Cancer Society.
Factors predicting response and survival in 149 patients with unresectable hepatocellular carcinoma treated by combination cisplatin, interferon‐alpha, doxorubicin and 5‐fluorouracil chemotherapy
Authors: Leung Thomas W. T. , Tang Amanda M. Y. , Zee Benny , Yu Simon C. H. , Lai Paul B. S. , Lau Wan Yee , Johnson Philip J.
Published: August 2002

BACKGROUND

The objective of the current study was to identify patient and disease related factors that influence response and survival for patients with unresectable hepatocellular carcinoma (HCC) who received a systemic combination chemotherapy consisting of cisplatin, alpha‐interferon, doxorubicin, and 5‐fluorouracil (PIAF).

METHODS

From July 1996 to February 1999, 149 patients with unresectable HCC were treated with PIAF: cisplatin (20mg/m2 intravenously, Days 1–4), doxorubicin (40mg/m2 intravenously, Day 1), 5‐fluorouracil (400mg/m2 intravenously, Days 1–4), and alpha‐interferon (5MU/m2 subcutaneously, Days 1–4), once every 3 weeks up to a maximum of six cycles. Univariate and multivariate analyses of patient and disease characteristics were used to identify factors predicting response and survival.

RESULTS

The objective response rate according to conventional criteria was 16.8% (complete response in 3 out of 149 patients, or 2%, 95% confidence interval [CI] 0–4.3%; partial response in 22 out of 149 patients, or 14.8%, 95% CI 9–20%). The median survival time was 30.9 weeks (95% CI 22.1 to 40). Significant independent predictors of an objective response were: absence of cirrhosis (P = 0.006), low bilirubin level (P = 0.006), and positive hepatitis C serology (P = 0.025). The following factors were related to a shorter survival time: high Okuda stage (P = 0.001), vascular involvement (P = 0.018), and cirrhosis (P = 0.008). Good risk patients (absence of cirrhosis and total bilirubin ≤ 0.6mg/dL) had an objective response rate of 50%.

CONCLUSIONS

Patients with unresectable HCC who also have normal total bilirubin and non‐cirrhotic livers have a better chance of response and prolonged survival after treatment with systemic PIAF. Cancer 2002;94:421–7. © 2002 American Cancer Society.