bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperthermia induces age‐dependent changes in rat hippocampal excitability
Authors: Liebregts Michelle T. , McLachlan Richard S. , Leung L. Stan
Published: October 2002

The mechanisms underlying the generation of febrile seizures are poorly understood. This study investigated hyperthermia‐induced changes in the hippocampus, a structure implicated in febrile seizures. It was hypothesized that neuronal excitability in the hippocampus changes with increasing temperature, and that this change is different in adult as compared with immature rats. Adult and immature (15–17 days postnatal) male rats were studied under urethane anesthesia during normothermia, moderate hyperthermia (38–39.5°C), and severe hyperthermia (>39.5°C). Paired‐pulse inhibition of the orthodromically activated population spikes in the dentate gyrus and cornu ammonis 1 region of the hippocampus (CA1), two structures within the hippocampus, was measured after stimulation of the medial perforant path and Schaffer collaterals, respectively. In the adult rat, paired‐pulse inhibition was increased in the dentate gyrus during moderate and severe hyperthermia but decreased in CA1 during severe hyperthermia (all p values < 0.05). In the immature rat, paired‐pulse inhibition was unchanged in the dentate gyrus but decreased in CA1 during moderate hyperthermia (p < 0.05). We suggest that hyperthermia contributes to seizure susceptibility in the immature hippocampus by decreasing CA1 inhibition. In the adult rat, a decrease in CA1 inhibition requires a higher degree of hyperthermia, and hippocampal seizure generation is opposed by an increase in dentate gyrus inhibition.
Midodrine in neurally mediated syncope: A double‐blind, randomized, crossover study
Authors: Kaufmann Horacio , Saadia Daniela , Voustianiouk Andrei
Published: October 2002

Neurally mediated syncope is the most frequent cause of syncope in patients without structural heart disease. Its most common trigger is a reduction in venous return to the heart due to excessive venous pooling in the legs. We conducted a double‐blind, randomized, crossover trial to investigate the efficacy of midodrine, a selective α‐1 adrenergic agonist that decreases venous capacitance, in preventing neurally mediated syncope triggered by passive head‐up tilt. Twelve patients with history of recurrent neurally mediated syncope, which was reproduced during head‐up tilt, were randomized to receive a nonpressor dose of midodrine (5mg) or placebo on day 1 and the opposite on day 3. One hour after drug or placebo administration, patients underwent 60‐degree head‐up tilt lasting 40 minutes (unless hypotension or bradycardia developed first). In the supine position, midodrine produced no significant change in blood pressure or heart rate. The responses to head‐up tilt were significantly different on the midodrine and the placebo day: on the placebo day, 67% (8/12) of the subjects suffered neurally mediated syncope, whereas only 17% (2/12) of the subjects developed neurally mediated syncope on the midodrine day (p < 0.02). These results indicate that midodrine significantly improves orthostatic tolerance during head‐up tilt in patients with recurrent neurally mediated syncope.
Thermal properties of Bombyx mori silk fibers
Authors: Zhang Han , Magoshi Jun , Becker Mary , Chen Jie Yu , Matsunaga Ryuji
Published: October 2002

The thermal properties of Bombyx mori silk fibers subjected to heat treatment were examined by thermogravimetry, differential thermal analysis, Fourier transform infrared absorption spectrometry (TG‐DTA‐FTIR) and scanning electron microscopy (SEM). The color, size, and shape of B. mori cocoon shells were observed as they were heated from 25 to 550°C. Only 1% of the original cocoon shell weight remains as cocoon ash after treatment at 550°C. Inorganic components, such as calcium, potassium, sulfur, magnesium, etc., were detected in the cocoon ash by energy dispersion fluorescent X‐ray spectrometry. A sharp decrease in weight was observed in the TG data beginning around 280°C, and an endothermic peak appeared at 308°C, as evidenced by the DTA curves. The IR bands observed at 2380 cm−1 (OH stretching), 1760 cm−1 (CO stretching), 1503 (NH stretching), 1085 cm−1 (CN stretching) and 965 cm−1 (NH2 stretching) become stronger as an exothermic reaction beginning at 280°C takes place. This is probably due to cleavage of the main chain and the accompanying decomposition of the silk fibers. Similarly, a SEM micrograph of silk fibers treated at 300°C shows a microtubule in the middle of the silk fibers of about 25‐μm diameter. This suggests that the thermal reactions starts in the middle of the silk fiber and forms a microtubule. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1817–1820, 2002
High‐resolution carbon‐13 nuclear magnetic resonance study of natural resins
Authors: Silva Emerson O. , Tavares Maria I. B. , Bathista André L. B. S. , Filho Nicolau P. , Nogueira José S.
Published: October 2002

Developing a methodology of analysis for the identification of the components presented in natural resins without a previous isolation or treatment, we first chose to use liquid nuclear magnetic resonance(NMR) to assign the main components. However, solid‐state NMR techniques give much more information about the chemical components presents in the resins than solution NMR, so we changed the methodology. The first approach must be the application of solid‐state NMR techniques and continuation of the identification process by analysis of the data obtained. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1848–1854, 2002
Chemical and thermal characterization of high‐ and low‐density irradiated polyethylenes
Authors: Sáenz De Juano‐Arbona V. , Vallés‐Lluch A. , Contat‐Rodrigo L. , Ribes‐Greus A.
Published: October 2002

A comparative study of the dynamic mechanical relaxation spectra of high‐ and low‐density polyethylenes irradiated with γ‐radiation from a Co60 source was performed. The irradiation doses ranged from 0 to 100 Mrad. All the samples were previously characterized by determination of the molecular weight distribution, the number of functional groups, and the crystalline fraction. All the relaxation zones between −145°C and the melt were studied in the frequency range from 0.3 to 30 Hz. The changes observed in the mechanical relaxation spectra were related to modifications in the chemical structure and morphological parameters attributed to the exposure of the samples to the γ‐radiation. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1953–1958, 2002
Free‐radical graft copolymerization of phosphonated methacrylates onto low‐density polyethylene
Authors: Gaboyard Manuel , Robin Jean‐Jacques , Hervaud Yves , Boutevin Bernard
Published: October 2002

Dimethyl 2‐methacryloxyethylphosphonate, its monosodium salt, and methyl 2‐methacryloyloxyethylphosphonic acid were synthesized, characterized, and grafted onto low‐density polyethylene (LDPE) powder under melt‐processing conditions in a Rheocord batch mixer (Karlsruhe, Germany). We studied the graft copolymerization onto LDPE in the presence of free‐radical initiators, benzoyl peroxide, and dicumyl peroxide, and we performed grafting onto ozone‐pretreated LDPE without any free‐radical initiator. Effects of reaction time, initiator concentration, and reaction temperature were studied. The possibility of modifying LDPE in the molten state with phosphonated methacrylates was clearly demonstrated. Graft copolymers were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and water contact angles. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2011–2020, 2002
Morphology and properties of cellulose/chitin blends membranes from NaOH/thiourea aqueous solution
Authors: Zhang Lina , Guo Ji , Du Yuming
Published: October 2002

Blend membranes of chitin/cellulose from 12 : 50 to 12 : 250 were successfully prepared from cotton linters in 1.5M NaOH/0.65M thirourea solution system. Two coagulation systems were used to compare with each other, one coagulating by 5 wt % H2SO4 (system H), and the other by 5 wt % CaCl2 and then 5 wt % H2SO4 (system C). The morphology, crystallinity, thermal stabilities, and mechanical properties of the blend membranes were investigated by electron scanning microscopy, atomic absorption spectrophotometer, infrared spectroscope, elemental analysis, X‐ray diffraction, different scanning calorimeter, and tensile tests. The cellulose/chitin blends exhibited a certain level of miscibility in the weight ratios tested. There were great differences between the two blends H coagulated with H2SO4 and C coagulated with CaCl2 and H2SO4, respectively. The membranes H have a denser structure, higher thermal stability, tensile strength (σb), and crystallinity (χc), and values of σb (90 MPa for chitin/cellulose 12 : 150) were significantly superior to that of both chitin and regenerated cellulose membrane. However, the blend membranes C have much better breaking elongations (ϵ) than that of membranes H, and relatively large pore size (2re = 210 μm), owing to the removal of a water‐soluble calcium complex of chitin as pore former from the membranes C. When the percentage content of chitin in the blends was from 5 to 7.5%, the values of breaking elongation for the blend membranes H and C all were higher than that of unblend membranes, respectively. The blends provide a promising way for application of chitin as a functional film or fiber in wet and dry states without derivates. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2025–2032, 2002
Characterization of multiplets in a Nd3+‐doped polymer optical fiber with low ion concentration
Authors: Zhao Hui , Chen Biao , Cao Yanping , Zhang Qijin , Yang Bao , Ming Hai , Xie Jianping
Published: October 2002

A new model is established to infer a ratio of multipleted ions to the total ions (ρ) based on rate equations of ionic transferring between excited and unexcited states, which is designed for rare earth containing polymer optical fiber (POF) with low ion concentration ranging from 30 to 200 ppm. A step‐index (SI) Nd3+‐doped POF was made from a preform which was prepared by using bulk polymerization of methyl methacrylate (MMA) with a certain amount of neodymium octanoate (NOA) as a dopant, 2,2‐azoisobutyronitrile (AIBN) as an initiator, and n‐butyl mercaptan as a chain‐transfer agent. The measurement of transmission at 810 nm of the Nd3+‐doped POF was made by fitting experimental data and by using the theoretical model, the values of ρ at different Nd3+ concentration could be obtained. The result showed that the ratio is 0.03, 0.08, and 0.3 for Nd3+‐doped POF at Nd3+ concentrations of 70, 100, and 200 ppm, respectively. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2033–2040, 2002
A study of mass transport of linear polystyrene in polyethyl methacrylate gel by dynamic light scattering
Authors: Zuo Ju , Huang Jianfeng , An Yingli , Li Fangxing , Zhu Changying , Zhang Jie , Zhang Zhiguang , He Binglin
Published: October 2002

Mass [i.e., linear polystyrene (PS) probe] transports in polyethyl methacrylate (PEMA) gels with ethylene dimethacrylate (EDMA) as crosslinker were studied by dynamic light scattering (DLS). For PEMA gels in toluene, we have established that it is a very well matched system, so that it is very convenient to study the mass transport of the PS macromolecule in such a system. Experiments show that the obstruction effects of PEMA gels for the mass transport of PS are obvious. Reasonably, the lower the gel obstruction for mass transport, the higher the diffusion coefficient Dt of PS in gel. Moreover, the larger the molecular weight of PS, the greater the obstruction effect of the gel. Furthermore, we traced quantitatively the evolution of Dt of PS during the crosslinking copolymerization of PEMA. The results show that, after the reaction, the obstacle for mass transport in the gel develops gradually. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2062–2066, 2002
The importance of exposed riverine sediments for phytophagous beetles (Coleoptera) in Scotland and northern England
Authors: Eyre M.D. , Luff M.L. , Lott D.A.
Published: October 2002

The distribution of phytophagous beetle assemblages on exposed riverine sediments (ERS) was investigated using 164 species lists from sites in four river catchments in Scotland and northern England.

The major influences affecting assemblage distribution were differences in highland and lowland catchment types and within these catchments the amount of vegetation cover. The position of sites within catchments was also important, with differences between tributary and upstream ERS and sites further downstream. Sediment composition had little influence.

River straightening and impoundments had a significant effect on the distribution of species assemblages.

A number of nationally rare and scarce species were recorded indicating that ERS appear to be important areas of relatively natural habitat within highly managed landscapes. The habitat diversity of phytophagous assemblages throughout the four catchments differed from that with other beetle groups sampled on the same sites.

ERS appear to be important sites for phytophagous beetles and the presence of nationally rare and scarce species increases ERS conservation value on sites usually considered important for other invertebrate groups.

Copyright © 2002 John Wiley & Sons, Ltd.
Non‐perceptible body current ELF effects as defined by electric shock safety data
Authors: Bridges Jack E.
Published: October 2002

Non‐perceptible body currents that arise from contacting exposed conductors that are part of household appliances, are considered in the light of past electric shock safety studies. When these appliances are touched, the older, nongrounded appliances exhibited orders of magnitude greater in‐tissue electric fields than the newer grounded appliances or other grounded, exposed, household conductors, such as water faucets. Bioelectromagnetics 23:542–544, 2002. © 2002 Wiley‐Liss, Inc.
Calcite microcrystals in the pineal gland of the human brain: First physical and chemical studies
Authors: Baconnier Simon , Lang Sidney B. , Polomska Maria , Hilczer Bozena , Berkovic Garry , Meshulam Guilia
Published: October 2002

A new form of biomineralization has been studied in the pineal gland of the human brain. It consists of small crystals that are less than 20 μm in length and that are completely distinct from the often observed mulberry‐type hydroxyapatite concretions. A special procedure was developed for isolation of the crystals from the organic matter in the pineal gland. Cubic, hexagonal, and cylindrical morphologies have been identified using scanning electron microscopy. The crystal edges were sharp whereas their surfaces were very rough. Energy dispersive spectroscopy showed that the crystals contained only the elements calcium, carbon, and oxygen. Selected area electron diffraction and near infrared Raman spectroscopy established that the crystals were calcite. With the exception of the otoconia structure of the inner ear, this is the only known nonpathological occurrence of calcite in the human body. The calcite microcrystals are probably responsible for the previously observed second harmonic generation in pineal tissue sections. The complex texture structure of the microcrystals may lead to crystallographic symmetry breaking and possible piezoelectricity, as is the case with otoconia. It is believed that the presence of two different crystalline compounds in the pineal gland is biologically significant, suggesting two entirely different mechanisms of formation and biological functions. Studies directed toward the elucidation of the formation and functions, and possible nonthermal interaction with external electromagnetic fields are currently in progress. Bioelectromagnetics 23:488–495, 2002. © 2002 Wiley‐Liss, Inc.
Application of multi‐parameter flow cytometry using fluorescent probes to study substrate toxicity in the indene bioconversion
Authors: Amanullah A. , Hewitt C. J. , Nienow A. W. , Lee C. , Chartrain M. , Buckland B. C. , Drew S. W. , Woodley J. M.
Published: October 2002

The bioconversion of indene to cis‐(1S,2R) indandiol, a potential key intermediate in the synthesis of Merck's HIV protease inhibitor, CRIXIVAN™, can be achieved using a Rhodococcus strain. This study using Rhodococcus I24 reports on the application of multiparameter flow cytometry for the measurement of cell physiological properties based on cytoplasmic membrane (CM) integrity and membrane depolarization as indicators of toxic effects of the substrate, indene. Quantification of intact polarized CM, intact depolarized CM and permeabilized CM of a large population of bacterial cells has been conducted using specific intracellular and membrane‐binding fluorescent stains. Measurements of oxygen uptake rate (OUR) and optical density (OD) as indicators of metabolic activity and biomass growth, respectively, were also made. Indene concentrations of up to 0.25 g/L (0.037 g indene/g dry cell weight) did not significantly (<5% compared to control) affect cell light‐scattering properties, intact CM, membrane polarization, respiratory activity, or biomass growth. Between this value and 1.5 g/L (0.221 g indene/g dry cell weight), the changes in intact CM, respiratory activity and biomass growth were relatively insignificant (<5% compared to control), although dissipation of the membrane potential of a significant proportion of the cell population occurred at 0.50 g/L (0.074 g indene/g dry cell weight). At 2.5 g/L (0.368 g indene/g dry cell weight) there was a significant increase in the dead cell population, accompanied by changes in the extracellular cationic concentrations and substantial decrease in respiratory activity. The primary effect of indene toxicity was the disruption of the proton motive force across the cytoplasmic membrane which drives the formation of ATP. The disruption of the proton motive force may have been due to the measured changes in proton permeability across the membrane. In addition, indene may have directly inhibited the membrane‐bound enzymes related to respiratory activity. The overall consequence of this was reduced respiratory activity and biomass growth. The cell physiological properties measured via flow cytometry are important for understanding the effects of toxicity at the cellular level which neither measurements of biomass growth or indandiol formation rates can provide since both are cell averaged measurements. The technique described here can also be used as a generic tool for measuring cell membrane properties in response to toxicity of other indene‐resistant strains that may be possible to use as recombinant hosts to perform the biotransformation of indene. This study has demonstrated that flow cytometry is a powerful tool for the measurement of cell physiological properties to assess solvent toxicity on whole cell biocatalysts. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 239–249, 2002.
Stability and linearization: discrete‐time systems
Authors: Sandberg Irwin W.
Published: October 2002

A theorem by Hadamard gives a two‐part condition under which a map from one Banach space to another is a homeomorphism. The theorem, while often very useful, is incomplete in the sense that it does not explicitly specify the family of maps for which the condition is met. Recently, under a typically weak additional assumption on the map, it was shown that Hadamard's condition is met if and only if the map is a homeomorphism with a Lipschitz continuous inverse. Here an application is given concerning the relation between the stability of a discrete‐time non‐linear system and the stability of related linear systems. Copyright © 2002 John Wiley & Sons, Ltd.
Targeting APP metabolism for the treatment of Alzheimer's disease
Authors: Sambamurti Kumar , Hardy John , Refolo Lorenzo M. , Lahiri Debomoy K.
Published: October 2002

Senile plaques consisting largely of extracellular deposits of a 38–42 residue peptide, amyloid β protein (Aβ) and intraneuronal deposits of the microtubule‐associated protein, tau, as neurofibrillary tangles (NFT) are defining features of Alzheimer's disease (AD). Aβ is produced after cleavage of a larger Aβ protein precursor (APP) by β‐secretase to the secreted sAPPβ and cell‐associated CTFβ followed by cleavage of CTFβ by γ‐secretase to secreted Aβ and the cognate cytoplasmic fragment, CTFγ. Most Aβ is 40 residues long, but a small fraction is 42–43 residues in length. A currently favored hypothesis is that Aβ42 forms toxic aggregates that induce NFT formation and ultimately the neuronal dysfunction characteristic of AD. Based on this hypothesis, the popular targets for drug development are the enzymes that generate or degrade Aβ42, block Aβ aggregation or toxicity and other factors that regulate these pathways in the brain. This article examines the evidence supporting the amyloid hypothesis and alternative hypotheses based on APP metabolism. In addition, the current drug targets for modifying APP metabolism to reduce Aβ42 are discussed. We further discuss evidence that suggests that other APP fragments such as CTFγ are altered by tested familial AD mutations and their role in AD pathogenesis needs to be carefully examined. We conclude that it is important to develop drugs based on alternative APP fragments (i.e., CTFγ) as well as the other identified pathways (i.e., oxidative stress) to provide alternatives if antiamyloid drugs fail to treat AD. Drug Dev. Res. 56:211–227, 2002. © 2002 Wiley‐Liss, Inc.
Genetic determination of biological age in the mennonites of the midwestern United States
Authors: Duggirala Ravindranath , Uttley Meredith , Williams Ken , Arya Rector , Blangero John , Crawford Michael H.
Published: October 2002

Numerous studies have shown that longevity is moderately heritable in human populations. Longevity, however, contains limited information on functional status, since individuals may exhibit differential survival patterns. In this study, we employed a stepwise multiple regression approach to estimate biological aging in a Mennonite population, using chronological age as a dependent variable and various predictors of chronological age including subphenotypes related to diabetes, coronary heart disease, hypertension, renal function, and markers of functional ability. The residual (the difference between chronological and predicted ages) is considered a marker of biological age. In fact, two different data sets were used to obtain residuals due to the availability of data. In each analysis, chronological age was regressed on predictor variables in a stepwise manner, retaining the variables significant at the 5% level. The first analysis (N=729) included 6 significant predictors (R2=44.3%): glucose, blood urea nitrogen (BUN), cholesterol, albumin, systolic blood pressure (SBP), and ln potassium, and the second analysis (N=232) included 9 significant predictors (R2=71.5%): BUN, albumin, SBP, low‐density lipoprotein cholesterol, forced expiratory volume in 1 sec (FEV1), grip strength, trunk flexibility, reaction time, and FEV1×sex. Using a variance components approach, we found that the data set‐specific residuals were significantly heritable (h2±SE): first analysis=0.265±0.106, and second analysis=0.469±0.180. The residuals from the second data set appear to be more informative for biological aging, perhaps due to the inclusion of functional ability‐related phenotypes in addition to the blood chemistry variables. In summary, we have shown that markers of biological aging in Mennonites are under substantial additive genetic influences. Genet. Epidemiol. 23:97–109, 2002. © 2002 Wiley‐Liss, Inc.
On a general class of conditional tests for family‐based association studies in genetics: the asymptotic distribution, the conditional power, and optimality considerations
Authors: Lange Christoph , Laird Nan M.
Published: October 2002

Family‐based association tests (FBATs) provide simple and powerful tests to detect association between a genetic marker and a disease‐susceptibility locus, manifest in subjects by a phenotype or disease trait. Here we propose a new class of conditional tests for family‐based association studies that includes most of the established tests and their generalizations. The class of tests is very general; it can be applied to longitudinal and multivariate traits or phenotypes, multiple genetic markers, and many other situations not yet discussed in the literature. For any test in this class, we derive the asymptotic distribution under the null hypothesis, the conditional power under any alternative hypothesis, and the optimal offset for single degree of freedom tests. The proposed methodology is illustrated with a genetic study of asthma. Genet. Epidemiol. 23:165–180, 2002. © 2002 Wiley‐Liss, Inc.
The pattern of expression of Mn and Cu‐Zn superoxide dismutase varies among squamous cell cancers of the lung, larynx, and oral cavity
Authors: Piyathilake Chandrika J. , Bell Walter C. , Oelschlager Denise K. , Heimburger Douglas C. , Grizzle William E.
Published: October 2002

Background

Despite the importance of reactive oxygen species (ROS) in the development of smoking‐related cancers, little is known about the pattern of expression of ROS scavengers in these cancers.

Methods

In this present study, we examined the expression of manganese superoxide dismutase (Mn‐SOD) and copper/zinc superoxide dismutase (Cu‐Zn‐SOD), which are essential enzymes that eliminate ROS, in squamous cell cancers (SCCs) of the lung (n = 12), larynx (n = 13), and oral cavity (n = 20).

Results

SCCs of larynx and oral cavity showed significantly enhanced immuhistochemical expression of Mn‐SOD compared with the matched uninvolved epithelium. The higher expression of Mn‐SOD was shown to be late and early events in the process of SCC development in the larynx and the oral cavity, respectively. The expression of Mn‐SOD in SCCs of the lung was significantly lower compared with luminal cells of the uninvolved epithelium but not compared with basal cells or an average expression of SOD in basal and luminal cells. The expression of both Mn‐SOD and cytoplasmic or nuclear Cu‐Zn‐SOD in bronchial epithelium adjacent to invasive cancer was significantly lower compared with its expression in the uninvolved bronchial epithelium away from cancer. This resulted in a significant difference in SOD expression between cancer and uninvolved bronchial epithelium away from cancer but not between cancer and uninvolved epithelium adjacent to cancer.

Conclusions

There are significant differences in the expression of Mn‐SOD and Cu‐Zn‐SOD among SCCs of the lung, larynx, and oral cavity. The results also suggest that variations in distance between cancer and uninvolved tissues evaluated could contribute to conflicting results of SOD expression. © 2002 Wiley Periodicals, Inc. Head Neck 24: 859–867, 2002
Human papillomavirus and p53 mutational status as prognostic factors in head and neck carcinoma
Authors: Sisk Elizabeth A. , Soltys Scott G. , Zhu Shaobo , Fisher Susan G. , Carey Thomas E. , Bradford Carol R.
Published: October 2002

Background

Mutations of the p53 tumor‐suppressor gene are common in squamous cell carcinoma of the head and neck (SCCHN) and may portend a worse prognosis. Human papillomavirus (HPV) represents another potential prognostic factor for SCCHN. The oncogenic potential of HPV may be due to the ability of its E6 oncoprotein to promote degradation of wild‐type p53 protein. We wish to determine whether there is a lower incidence of p53 mutations in HPV‐positive versus HPV‐negative tumors, and if HPV and/or p53 status has an impact on survival.

Methods

Thirty‐two SCCHN specimens were analyzed for mutations of the p53 gene using single‐strand conformational polymorphism (SSCP) analysis followed by DNA sequencing. The HPV status of all specimens was evaluated by use of polymerase chain reaction with HPV consensus primers and Southern blot hybridization. Pertinent clinical information was obtained from chart review.

Results

Nonsilent p53 mutations were present in 2 of 15 (13%) of HPV‐positive tumors compared with 6 of 17 (35%) of HPV‐negative tumors (p = .229; Fisher's exact test, odds ratio .28). A survival advantage was found between HPV‐positive compared with HPV‐negative specimens (p = .0264) and between p53 wild type compared with p53 mutant specimens (p = .01) by univariate log rank analysis. When stratified according to both HPV and p53 status, a statistically significant survival difference was observed largely because of a 100% survival for the HPV‐positive/p53 wild‐type group (p = .003).

Conclusions

This preliminary study supports the notion that the presence of HPV confers a survival advantage among HNSCC patients, particularly when p53 is wild type. © 2002 Wiley Periodicals, Inc. Head Neck 24: 841–849, 2002
Developing competency models to promote integrated human resource practices
Authors: Rodriguez Donna , Patel Rita , Bright Andrea , Gregory Donna , Gowing Marilyn K.
Published: October 2002

Today, competencies are used in many facets of human resource management, ranging from individual selection,
development, and performance management to organizational strategic planning. By incorporating competencies into
job analysis methodologies, the Office of Personnel Management (OPM) has developed robust competency
models that can form the foundation for each of these initiatives. OPM has placed these models into automated
systems to ensure access for employees, human resources professionals, and managers. Shared access to the data
creates a shared frame of reference and a common language of competencies that have provided the basis for
competency applications in public sector agencies. © 2002 Wiley Periodicals, Inc.
Selecting the best and brightest: Leveraging human capital
Authors: O'Leary Brian S. , Lindholm Mary Lou , Whitford Richard A. , Freeman Stephen E.
Published: October 2002

This article provides a brief discussion of the changing nature of work and describes how automation and the Internet are changing the way the U.S. government recruits and hires employees. The authors discuss the validity of various assessment methods used to select and promote employees and the return on investment that can result from using valid assessment techniques. The authors review several illustrative assessment programs used in the federal government. Finally, the authors explore the next generation of assessments. © 2002 Wiley Periodicals, Inc.
Presentation of native TROP‐2 tumor antigens to human cytotoxic T lymphocytes by engineered antigen‐presenting cells
Authors: Mangino Giorgio , Grazia Capri Maria , Barnaba Vincenzo , Alberti Saverio
Published: October 2002

Professional antigen‐presenting cells (APC), e.g. dendritic cells, express immuno‐proteasome components and process proteins for MHC presentation differently from non‐immune cells. Thus, they induce reactivities against sets of peptides that do not overlap with those generated by non‐professional APC, i.e., tumor cells, and stimulate cytotoxic T lymphocytes (CTL) that may not recognize them. The goal of this work was to establish a system for antigen presentation and in vitro stimulation of human CTL using “tumor‐cell‐like” engineered APC. Murine fibroblasts were transfected with human HLA Class I alleles, together with the B7.1, ICAM‐1 and germ‐line TROP2 genes. The last encodes a cell surface glycoprotein widely expressed by human cancers. Unseparated peripheral blood mononuclear cells from HLA Class I‐matched individuals were stimulated in vitro by the engineered APC. These efficiently induced the activation and proliferation of antigen‐specific HLA‐restricted CTL lines and clones. The Trop‐2‐specific CTL demonstrated high specific cytotoxicity against the appropriate transfected target cells. They also efficiently lysed MCF‐7 human tumor cells expressing endogenous HLA‐A2.1, Trop‐2 together with ICAM‐1. These results demonstrate that Trop‐2 is a target molecule recognized by human CTL. Moreover, they demonstrate that non‐immune engineered APC efficiently process and present native tumor‐specific proteins in the context of human MHC Class I, and stimulate the growth and cytotoxicity of specific anti‐tumor CTL. © 2002 Wiley‐Liss, Inc.
Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane‐induced colon carcinogenesis in male F344 rats
Authors: Kohno Hiroyuki , Tanaka Takuji , Kawabata Kunihiro , Hirose Yoshinobu , Sugie Shigeyuki , Tsuda Hiroyuki , Mori Hideki
Published: October 2002

The modifying effect of dietary administration of the polyphenolic antioxidant flavonoid silymarin, isolated from milk thistle [Silybum marianum (L.) Gaertneri], on AOM‐induced colon carcinogenesis was investigated in male F344 rats. In the short‐term study, the effects of silymarin on the development of AOM‐induced colonic ACF, being putative precursor lesions for colonic adenocarcinoma, were assayed to predict the modifying effects of dietary silymarin on colon tumorigenesis. Also, the activity of detoxifying enzymes (GST and QR) in liver and colonic mucosa was determined in rats gavaged with silymarin. Subsequently, the possible inhibitory effects of dietary feeding of silymarin on AOM‐induced colon carcinogenesis were evaluated using a long‐term animal experiment. In the short‐term study, dietary administration of silymarin (100, 500 and 1,000 ppm in diet), either during or after carcinogen exposure, for 4 weeks caused significant reduction in the frequency of colonic ACF in a dose‐dependent manner. Silymarin given by gavage elevated the activity of detoxifying enzymes in both organs. In the long‐term experiment, dietary feeding of silymarin (100 and 500 ppm) during the initiation or postinitiation phase of AOM‐induced colon carcinogenesis reduced the incidence and multiplicity of colonic adenocarcinoma. The inhibition by feeding with 500 ppm silymarin was significant (p < 0.05 by initiation feeding and p < 0.01 by postinitiation feeding). Also, silymarin administration in the diet lowered the PCNA labeling index and increased the number of apoptotic cells in adenocarcinoma. β‐Glucuronidase activity, PGE2 level and polyamine content were decreased in colonic mucosa. These results clearly indicate a chemopreventive ability of dietary silymarin against chemically induced colon tumorigenesis and will provide a scientific basis for progression to clinical trials of the chemoprevention of human colon cancer. © 2002 Wiley‐Liss, Inc.
Epstein‐Barr virus antagonizes the antiproliferative activity of transforming growth factor‐β but does not abolish its signaling
Authors: Horndasch Manuela , Raschke Eva E. , Bommer Guido , Schuhmacher Marino , Dumont Elisabeth , Kuklik‐Roos Conny , Eick Dirk , Kempkes Bettina
Published: October 2002

TGF‐β induces apoptosis and inhibits the proliferation of EBV‐negative B‐lymphoma cell lines. In contrast, EBV‐immortalized B cells are resistant to both the proapoptotic and the antiproliferative activities of TGF‐β. We have generated a lymphoblastoid cell line, in which we can switch on and off the EBV‐specific transcriptional program driven by EBNA2. When these cells express the EBNA2‐driven phenotype, they are resistant to TGF‐β‐mediated growth arrest. We used this cell line to readdress the question of how EBV can overcome the antiproliferative TGF‐β activity. We show here that EBV‐driven cells remain TGF‐β‐responsive since TGF‐β target genes are readily induced. Thus, EBV can overcome TGF‐β‐mediated growth arrest without interfering with the core machinery of the TGF‐β signaling pathway, which links ligand binding to the induction of TGF‐β target genes. © 2002 Wiley‐Liss, Inc.
Interval cancers following breast cancer screening in Singaporean women
Authors: Gao Fei , Chia Kee‐Seng , Ng Fook‐Cheong , Ng Erg‐Hen , Machin David
Published: October 2002

Our study reports on the interval cancers arising in the subsequent 3 years in women screened as part of the Singapore Breast Cancer Screening Programme that commenced in 1994. Women, the majority of Chinese ethnicity, were either invited or not invited by random allocation to be screened. All women, other than those identified with breast cancer at screening, whether invited or not, were followed for 3 years, and information on all breast cancers arising in this period was obtained through the national registry. In particular, the cancers arising from those women who were deemed free of the disease at screening were noted. The mammographs taken at screening of those women who developed such an interval cancer were rereviewed by 3 radiologists. In the 28,099 women who were screened and deemed free of disease, 59 interval cancers were reported with annual rates of 2.1, 10.6 and 10.8 per 10,000 women‐years in the succeeding 3‐year periods. In 39,425 women who were invited but declined screening, the rates were 17.0, 15.5 and 11.7, while the corresponding rates from 97,294 women not invited were 12.8, 13.3 and 13.0. Whereas the annual incidence at 1 year in women who have been screened is much lower than those in the 2 groups who were not screened, it is of a similar magnitude by 2 years. This suggests that locally an optimal screening interval may be close to 1 year. The rereview of the mammograms of those 59 women with interval cancers suggested that the maximum possible number of these that might have been detected at screening was 10 (17%). © 2002 Wiley‐Liss, Inc.
Isotype switch‐mediated CH deletions are a recurrent feature of Myc/CH translocations in peritoneal plasmacytomas in mice
Authors: Kovalchuk Alexander L. , Janz Siegfried
Published: October 2002

Oncogene activating chromosomal translocations that interrupt IGH switch (S) regions at 14q32 are thought to be caused by misguided IGH isotype switching in postgerminal center B‐cell lymphomas and plasma cell myelomas in humans. Aberrant switching also seems to be involved in altering the fine structure of the translocation in some of these tumors, but the significance of these changes is not known. Here we report on 3 cases of IL‐6 transgenic mouse plasmacytomas (PCT) that harbor T(12;15) translocations that had been modified by frustrated switch attempts that result in CH deletions. When considered together with 6 similar cases of PCT described previously, our observations suggest that secondary deletions in CH are a regular feature in the molecular evolution of T(12;15) translocations and, thereby, in the progression of PCT. We propose that the T(12;15)+ mouse PCT offers a uniquely valuable model system for elucidating the dual role of abnormal isotype switching in causation and ‘remodeling’ of chromosomal translocations. © 2002 Wiley‐Liss, Inc.
Direct ab initio dynamics study on the rate constants and kinetic isotope effect for the reactions of H atoms with GeDn(CH3)4−n (n = 1–4)
Authors: Wu Yang , Ding Yi‐Hong , Xiao Jing‐Fa , Li Ze‐Sheng , Huang Xu‐Ri , Sun Chia‐Chung
Published: October 2002

Direct ab initio dynamic calculations are performed on the reactions of atomic hydrogen with GeDn(CH3)4−n (n = 1–4) over the temperature range 200–2000 K at the PMP4SDTQ/6‐311 +G(3df,2p)//MP2/6‐31 +G(d) (for n = 2–4) and G2//MP2/6‐31 +G(d) (for n = 1) levels. The corresponding kH/kD ratios are then calculated in order to determine the kinetic isotope effect for the four reactions. For the simplest GeD4 +H reaction, the only one that has available experimental data, the calculated canonical variational transition state theory incorporates small‐curvature tunneling correction (CVT/SCT) thermal rate constants, and the kH/kD values are in good agreement with the experimental values within the experimental temperature range 293–550 K. For the four GeDn(CH3)4−4 (n = 1–4) reactions, the variational effect is small over the whole temperature range, whereas the small‐curvature effect is important in the lower temperature range. Finally, the overall rate constants are fitted to the three‐parameter expression over the whole temperature range 200–2000 K as 5.8 × 108T1.68exp(−929/T), 1.7 × 108T1.80exp(−691/T), 2.58 × 108T1.71exp(−706/T), and 1.0 × 107T2.08exp(−544/T) cm3 mol−1 s−1 for the n = 4, 3, 2, and 1 reactions. Our work may represent the first theoretical study of the kinetic isotope effect for the H‐attack on the GeH bonding. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1366–1374, 2002
Neuromodulation of arthropod mechanosensory neurons
Authors: Torkkeli Päivi H. , Panek Izabela
Published: October 2002

Arthropod mechanosensory afferents have long been known to receive efferent synaptic connections onto their centrally located axon terminals. These connections cause presynaptic inhibition by attenuating the action potentials arriving at the axon terminals, thus reducing the synaptic potentials in the postsynaptic neurons. This type of inhibition can specifically reduce the excitation of selected postsynaptic neurons while leaving others unaffected. However, recent research has demonstrated that sensory signals detected by arthropod mechanosensory neurons can also be synaptically modulated before they ever arrive at the axon terminals. In arachnids and crustaceans, wide and complex networks of synapses on all parts of the afferent neurons, including the somata and dendrites, provide mechanisms to inhibit or enhance the responses to mechanical stimuli as they are being detected. This modulation will affect the signal transmission to all axonal branches and postsynaptic cells of the affected receptor neuron. In addition to the increased complexity of mechanosensory information transmission produced by these synapses, a variety of circulating neuroactive substances also modulate these neurons by acting on their postsynaptic receptors. Microsc. Res. Tech. 58:299–311, 2002. © 2002 Wiley‐Liss, Inc.
Combined biochemistry and histocytochemistry as a tool to investigate Ecto‐ATPase in the cardiac muscle
Authors: Zinchuk Vadim S. , Okada Teruhiko , Seguchi Harumichi
Published: October 2002

Ecto‐ATPase (ecto‐adenosine triphosphatase), a key enzyme of cardiac metabolism, is responsible for modulation of the concentration of extracellular nucleotides in the heart. We present methodology consisting of the combined use of biochemical and histocytochemical techniques to study its properties. Using samples from essentially the same preparation, we applied biochemistry and histocytochemistry to determine biochemical characteristics of ecto‐ATPase and an in situ localization of its reactivity. Our results indicated that detected enzyme resists fixation, depends on divalent ions, and hydrolyzes ATP, but not AMP or ADP‐β‐S. Reaction product of the enzyme activity was found confined to the extracellular surface of the plasma membrane of cardiac myocytes and endothelial cells due to the corresponding orientation of the enzyme active sites. Experiments using an inhibitor justified specificity of the reaction. When used together with molecular biological and immunocytochemical techniques, the present methodological approach should be capable of yielding important information about the actual ability of ecto‐ATPase to operate. Microsc. Res. Tech. 58:427–431, 2002. © 2002 Wiley‐Liss, Inc.
Aminoglycoside‐derived cationic lipids as efficient vectors for gene transfection in vitro and in vivo
Authors: Belmont Philippe , Aissaoui Abderrahim , Hauchecorne Michelle , Oudrhiri Noufissa , Petit Laure , Vigneron Jean‐Pierre , Lehn Jean‐Marie , Lehn Pierre
Published: October 2002

Background

Cationic lipids are at present very actively investigated for gene transfer studies and gene therapy applications. Basically, they rely on the formation of DNA/lipid aggregates via electrostatic interactions between their cationic headgroup and the negatively charged DNA. Although their structure/activity relationships are not well understood, it is generally agreed that the nature of the positive headgroup impacts on their transfection activity. Thus, we have directed our efforts toward the development of cationic lipids with novel cationic moieties. In the present work, we have explored the transfection potential of the lipophilic derivatives of the aminoglycoside kanamycin A. Indeed, aminoglycosides, which are natural polyamines known to bind to nucleic acids, provide a favorable scaffold for the synthesis of a variety of cationic lipids because of their structural features and multifunctional nature.

Methods and results

We report here the synthesis of a cationic cholesterol derivative characterized by a kanamycin A headgroup and of its polyguanidinylated derivative. The amino‐sugar‐based cationic lipid is highly efficient for gene transfection into a variety of mammalian cell lines when used either alone or as a liposomal formulation with the neutral phospholipid dioleoylphosphatidylethanolamine (DOPE). Its polyguanidinylated derivative was also found to mediate in vitro gene transfection. In addition, colloidally stable kanamycin‐cholesterol/DOPE lipoplexes were found to be efficient for gene transfection into the mouse airways in vivo.

Conclusions

These results reveal the usefulness of cationic lipids characterized by headgroups composed of an aminoglycoside or its guanidinylated derivative for gene transfection in vitro and in vivo. Copyright © 2002 John Wiley & Sons, Ltd.
Gutted adenoviral vector growth using E1/E2b/E3‐deleted helper viruses
Authors: Barjot Catherine , Hartigan‐O'Connor Dennis , Salvatori Giovanni , Scott Jeannine M. , Chamberlain Jeffrey S.
Published: October 2002

Background

Helper‐dependent, or gutted, adenoviruses (Ad) lack viral coding sequences, resulting in reduced immunotoxicity compared with conventional Ad vectors. Gutted Ad growth requires a conventional Ad to supply replication and packaging functions in trans. Methods that allow high‐titer growth of gutted vectors while reducing helper contamination, and which use safer helper viruses, will facilitate the use of gutted Ad vectors in vivo.

Methods

Replication‐defective helper viruses were generated that are deleted for Ad E1, E2b and E3 genes, but which contain loxP sites flanking the packaging signal. Complementing Ad packaging cell lines (C7‐cre cells) were also generated by transfecting 293 cells with the Ad E2b genes encoding DNA polymerase and pre‐terminal protein, and with a cre‐recombinase plasmid.

Results

We show that C7‐cre cells allow efficient production of gutted Ad using ΔE1 + ΔE2b + ΔE3 helper viruses whose growth can be limited by cre‐loxP‐mediated excision of the packaging signal. Gutted Ad vectors carrying ∼28 kb cassettes expressing full‐length dystrophin were prepared at high titers, similar to those obtained with E2b+ helpers, with a resulting helper contamination of <1%.

Conclusions

These new packaging cell lines and helper viruses offer several significant advantages for gutted Ad vector production. They allow gutted virus amplification using a reduced number of passages, which should reduce the chances of selecting rearranged products. Furthermore, the residual helper contamination in gutted vector preparations should be less able to elicit immunological reactions upon delivery to tissues, since E2b‐deleted vectors display a profound reduction in viral gene expression. Copyright © 2002 John Wiley & Sons, Ltd.