bluuebunny/crossref_metadata_2025 huggingface dataset:
Lanthanum(III)‐Catalyzed Disproportionation of Hydrogen Peroxide: A Heterogeneous Generator of Singlet Molecular Oxygen—1O2 (1Δg)—in Near‐Neutral Aqueous and Organic Media for Peroxidation of Electron‐Rich Substrates
Authors: Nardello Véronique , Barbillat Jacques , Marko Jean , Witte Peter T. , Alsters Paul L. , Aubry Jean‐Marie
Published: January 2003

The decomposition of hydrogen peroxide into singlet molecular oxygen—1O2 (1Δg)—in the presence of lanthanum(iii) salts was studied by monitoring its characteristic IR luminescence at 1270 nm. The process was found to be heterogeneously catalyzed by LaIII, provided that the heterogeneous catalyst is generated in situ. The yield of 1O2 generation was assessed as 45±5 % both in water and in methanol. The pH‐dependence on the rate of 1O2 generation corresponds to a bell‐shaped curve from pH 4.5 to 13 with a maximum around pH 8. The study of the influence of H2O2 showed that the formation of 1O2 begins as soon as one equivalent of H2O2 is introduced. It then increases drastically up to two equivalents and more smoothly above. Unlike all other metal salt catalyst systems known to date for H2O2 disproportionation, this chemical source of 1O2 is able to generate 1O2 not only in basic media, but also under neutral and slightly acidic conditions. In addition, this La‐based catalyst system has a very low tendency to induce unwanted oxygenating side reactions, such as epoxidation of alkenes. These two characteristics of the heterogeneous lanthanum catalyst system allow non‐photochemical (i.e., “dark”) singlet oxygenation of substrate classes that cannot be peroxidized successfully with conventional molybdate catalysts, such as allylic alcohols and alkenyl amines.
A Three‐Component Reaction for Diversity‐Oriented Synthesis of Polysubstituted Piperidines: Solution and Solid‐Phase Optimization of the First Tandem Aza[4+2]/Allylboration
Authors: Touré Barry B. , Hoveyda Hamid R. , Tailor Jyoti , Ulaczyk‐Lesanko Agnieszka , Hall Dennis G.
Published: January 2003

This article describes the design and optimization of a simple three‐component aza[4+2]/allylboration reaction to access polysubstituted α‐hydroxyalkyl piperidines in a highly diastereocontrolled fashion from maleimides, 4‐boronohydrazonodienes, and aldehydes. The aldehyde component does not interfere with the first aza[4+2] step, and it was found that this tandem reaction provides better yields of piperidine products 5 when carried out in one‐pot. The required 4‐borono‐hydrazonodienes 1 are synthesized efficiently from the condensation of 3‐boronoacrolein pinacol ester (4) with hydrazines. Overall, the three‐component process using N‐substituted maleimides as dienophiles produces four stereogenic centers and is quite general. It tolerates the use of a wide variety of aldehydes and hydrazine precursors with different electronic and steric characteristics. By allowing such a wide substrate scope and up to four elements of diversity, this reaction process is particularly well adapted towards applications in diversity‐oriented synthesis of polysubstituted piperidine derivatives. The suitability of the aza[4+2]/allylboration reaction for use in solid‐phase chemistry was also demonstrated using a N‐arylmaleidobenzoic acid functionalized resin. This novel multicomponent reaction thus offers a high level of stereocontrol and versatility in the preparation of densely functionalized nitrogen heterocycles.
A Comprehensive Theoretical Study on the Reactions of Sc+ with CnH2n+2 (n=1–3): Structure, Mechanism, and Potential‐Energy Surface
Authors: Zhang Dongju , Liu Chengbu , Bi Siwei , Yuan Shiling
Published: January 2003

The reactions of Sc+(3D) with methane, ethane, and propane in the gas phase were studied theoretically by density functional theory. The potential energy surfaces corresponding to [Sc, Cn, H2n+2]+ (n=1–3) were examined in detail at the B3LYP/6‐311++G(3df, 3pd)//B3LYP/6‐311+G(d,p) level of theory. The performance of this theoretical method was calibrated with respect to the available thermochemical data. Calculations indicated that the reactions of Sc+ with alkanes are multichannel processes which involve two general mechanisms: an addition–elimination mechanism, which is in good agreement with the general mechanism proposed from earlier experiments, and a concerted mechanism, which is presented for the first time in this work. The addition–elimination reactions are favorable at low energy, and the concerted reactions could be alternative pathways at high energy. In most cases, the energetic bottleneck in the addition–elimination mechanism is the initial CC or CH activation. The loss of CH4 and/or C2H6 from Sc++CnH2n+2 (n=2, 3) can proceed along both the initial CC activation branch and the CH activation branch. The loss of H2 from Sc++CnH2n+2 (n=2, 3) can proceed not only by 1,2‐H2 and/or 1,3‐H2 elimination, but also by 1,1‐H2 elimination. The reactivity of Sc+ with alkanes is compared with those reported earlier for the reactions of the late first‐row transition‐metal ions with alkanes.
The Stabilisation of Monomeric Parent Compounds of Phosphanyl‐ and Arsanylboranes
Authors: Vogel Ulf , Hoemensch Petra , Schwan Karl‐Christian , Timoshkin Alexey Y. , Scheer Manfred
Published: January 2003

The structures of the parent compounds of phosphanyl‐ and arsanylboranes, H2BPH2 and H2BAsH2, were calculated by DFT‐B3LYP methods. Such compounds have not previously been obtained preparatively. By applying the concept of Lewis acid/base stabilisation, [(CO)5W(H2EBH2⋅NMe3)] (E=P (3), As (4)) derivatives have been synthesised by the metathesis reactions between Li[(CO)5WEH2] and ClH2BNMe3 (E=P, As). Comprehensive thermodynamic studies on these systems verify the high stability of the Lewis acid/base stabilised complexes. Unexpected based on the thermodynamic calculations, UV radiation of the phosphanylborane 3 leads to the dinuclear phosphanido‐bridged complex [(CO)8W2(μ‐PHBH2⋅NMe3)2] (5) by H2 and CO elimination.
Synthesis of an Amino‐Functionalized Model of the Fe‐Only Hydrogenase Active Site
Authors: Salyi Szabolcs , Kritikos Mikael , Åkermark Björn , Sun Licheng
Published: January 2003

A dinuclear 2Fe2S mimic 6 of the active site of the Fe‐only hydrogenases has been synthesized. Complex 6 contains a free amino group which enables linkage to a protein backbone or to a redox active species for the study of electron transfer processes in proteins or in supramolecular systems. The structures of the complex 6 and its Boc‐protected precursor 5 could be verified by X‐ray crystallography.
On the Cavitation Energy of Water
Authors: Höfinger Siegfried , Zerbetto Francesco
Published: January 2003

Free‐energy‐perturbation theory from molecular dynamics calculations has been used to obtain the ΔG of adjoining cavities' formation in water. The ΔGs for systems with three, five and seven cavities are compared with that of a single cavity of the same volume, and found to be in good agreement. The conditions under which the analytical formulation of the energy of cavity formation proposed by Pierotti holds are discussed. The data for a single cavity have been tabulated and can lend themselves to a simple numerical implementation in standard quantum chemical packages, which can be used when high accuracy for ΔGcav is required.
Sequestered Alkyllithiums: Why Phenyllithium Alone is Suitable for Betaine‐Ylide Generation
Authors: Wang Qian , Deredas Dariusz , Huynh Cyril , Schlosser Manfred
Published: January 2003

The key step in the trans‐selective modification of the Wittig reaction is the α‐lithiation of the lithium bromide coordinated ylide–aldehyde adduct (the so‐called “P‐betaine”). Only phenyllithium effects this deprotonation rapidly and cleanly. Alkyllithiums (in particular, butyl‐, sec‐butyl‐, and tert‐butyllithium) react only sluggishly and incompletely, being tied up in very stable mixed aggregates with the lithium alkoxide part of the betaines.
Vibronic Coupling in Molecules and in Solids
Authors: Grochala Wojciech , Hoffmann Roald , Edwards Peter P.
Published: January 2003

We utilize the experience gained in our previous studies on the “chemistry of vibronic coupling” in simple homonuclear and heteronuclear molecules to begin assembling theoretical guidelines for the construction of potentially superconducting solids exhibiting large electron‐phonon coupling. For this purpose we analyze similarities between vibronic coupling in isolated molecules and in extended solids. In particular, we study vibronic coupling along the antisymmetric stretch coordinate (Qas) in linear symmetric AAA molecules, and along the optical phonon “pairing” mode coordinate (Qopt) in corresponding one‐dimensional [A]∞ chains built of equidistant A atoms. This is done for a broad range of chemical elements (A). The following similarities between vibronic coupling in molecules and phonon coupling in solids emerge from our calculations: 1) The HOMO/LUMO electronic energy gap in an AAA molecule increases along Qas, and the highest occupied crystal orbital/lowest unoccupied crystal orbital gap in [A]∞ chain increases along Qopt. 2) The maximum vibronic instability is invariably obtained for a half‐filled, singly occupied molecular orbital in AAA molecules, and for a corresponding half‐filled band in [A]∞ chains. 3) The vibronic stability of an AAA molecule increases with a decrease of the AA bond length, as does the vibronic stability of [A]∞ chains (external pressure may lead to a reversal of a Peierls distortion). 4) The high degree of s–p mixing and ionic/covalent forbidden curve crossing dramatically enhance the vibronic instability of both AAA molecules and [A]∞ chains. We also introduce one quantitative relationship: The parameter log(R) (where R is molar refractivity, a parameter used by Herzfeld to prescribe the conditions for the metallization of the elements) correlates with a parameter fAA (defined as twice the electronegativity of A, divided by the equilibrium AA bond length), used by two of us previously to describe vibronic coupling in AAA molecules for a broad range of elements (A=halogen, H, or an alkali metal). We hope to illustrate that key chemical aspects of vibronic coupling in simple molecules may thus be profitably transferred to corresponding materials in the solid state.
GABAergic and glutamatergic axons innervate the axon initial segment and organize GABAA receptor clusters of cultured hippocampal pyramidal cells
Authors: Christie Sean B. , De Blas Angel L.
Published: January 2003

We have studied γ‐aminobutyric acid (GABA)A receptor (GABAAR) clustering within the axon initial segment (AIS) in low‐density cultures of hippocampal pyramidal cells following GABAergic and glutamatergic innervation of the AIS. Large, intensely fluorescent, and postsynaptic GABAAR clusters were present in the AIS. More than 95% of these clusters colocalized with presynaptic GABAergic or glutamatergic terminals, forming matched or mismatched synapses, respectively. Less than 5% of the GABAAR clusters of the AIS did not colocalize with GABAergic or glutamatergic terminals, suggesting that GABAARs normally do not form clusters unless the AIS received GABAergic or glutamatergic innervation. Few or no clusters of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionate (AMPA) receptors or the postsynaptic density‐95 protein (PSD‐95) were found in the AIS, even when the AIS was innervated by glutamatergic axons. Glutamatergic innervation of the AIS that formed mismatched synapses with postsynaptic GABAAR clusters mainly occurred when the AIS did not receive GABAergic innervation. However, when the AIS was innervated by GABAergic axons, the formation of matched GABAergic synapses predominated and coincided with large reductions in both the density of glutamatergic terminals from the AIS and the mismatching of GABAAR clusters. A similar effect was observed at axo‐dendritic synapses, where GABAergic innervation also led to a large decrease in mismatched GABAAR clusters and a smaller, but significant, decrease in glutamatergic terminal density in dendrites that received GABAergic innervation. We hypothesize that competition between GABAergic and glutamatergic innervation of the AIS in the intact hippocampus leads to the exclusive presence of GABAergic inhibitory synapses in the AIS of pyramidal cells. J. Comp. Neurol. 456:361–374, 2003. © 2003 Wiley‐Liss, Inc.
PDAPP; YFP double transgenic mice: A tool to study amyloid‐β associated changes in axonal, dendritic, and synaptic structures
Authors: Brendza Robert P. , O'Brien Cara , Simmons Kelly , McKeel Daniel W. , Bales Kelly R. , Paul Steven M. , Olney John W. , Sanes Joshua R. , Holtzman David M.
Published: January 2003

Neuritic plaques are one of the stereotypical hallmarks of Alzheimer's disease (AD) pathology. These structures are composed of extracellular accumulations of fibrillar forms of the amyloid‐β peptide (Aβ), a variety of other plaque‐associated proteins, activated glial cells, and degenerating nerve processes. To study the neuritic toxicity of different structural forms of Aβ in the context of regional connectivity and the entire cell, we crossed PDAPP transgenic (Tg) mice, a model with AD‐like pathology, to Tg mice that stably express yellow fluorescent protein (YFP) in a subset of neurons in the brain. In PDAPP; YFP double Tg mice, markedly enlarged YFP‐labeled axonal and dendritic varicosities were associated with fibrillar Aβ deposits. These varicosities were absent in areas where there were nonfibrillar Aβ deposits. Interestingly, YFP‐labeled varicosities revealed changes that corresponded with changes seen with electron microscopy and the de Olmos silver staining technique. Other silver staining methods and immunohistochemical localization of phosphorylated neurofilaments or phosphorylated tau were unable to detect the majority of these dystrophic neurites. Some but not all synaptic vesicle markers accumulated abnormally in YFP‐labeled varicosities associated with neuritic plaques. In addition to the characterization of the effects of Aβ on axonal and dendritic structure, YFP‐labeled neurons in Tg mice should prove to be a valuable tool to interpret the localization patterns of other markers and for future studies examining the dynamics of axons and dendrites in a variety of disease conditions in living tissue both in vitro and in vivo. J. Comp. Neurol. 456:375–383, 2003. © 2003 Wiley‐Liss, Inc.
Are there gender differences in the prescribing of hypnotic medications for insomnia?
Authors: Brownlee K. , Devins G. M. , Flanigan M. , Fleming J. A. E. , Morehouse R. , Moscovitch A. , Plamondon J. , Reinish L. , Shapiro C. M.
Published: January 2003

Gender differences in the prescribing patterns of general classes of medications for insomnia were examined. The classes of medications included: zopiclone, antidepressants, benzodiazepines, antihistamines and no medication. The sample comprised a sub‐set of respondents from 2620 questionnaires of the Canadian Multicentre Sleep Database. Respondents for this database were contacted through physicians, announcements in the media and local pharmacies. The results indicated that gender alone was not associated with differential prescribing for insomnia, nor was gender associated with patterns of medication use such as frequency of taking medication, length of use, taking more or less medication than prescribed or attempts to stop taking medication. Demographic factors were included in the analysis and age and marital status were associated with different prescribing patterns for men and women with insomnia. It is possible that physicians refer to stereotypic expectations when prescribing hypnotics. Copyright © 2002 John Wiley & Sons, Ltd.
Cognitive effects of long‐term benzodiazepine use in older adults
Authors: Pat McAndrews Mary , Weiss Rachel T. , Sandor Paul , Taylor Ann , Carlen Peter L. , Shapiro Colin M.
Published: January 2003

This study examined the potential for cognitive morbidity associated with the long‐term use of benzodiazepine (BZ) sedative‐hypnotics in a sample of healthy older adults. Tests of memory, attention and processing speed were conducted prior to and 1 month after drug discontinuation for 25 BZ‐users and at similar intervals for 26 healthy control subjects. After controlling for differences in affective status between BZ‐users and controls, there were no significant group differences in cognitive performance. However, BZ‐users showed greater gains on tests of attention and speed of processing at repeat testing compared with controls this improvement was not attributable to a change in affective status. These findings suggest that there may be subtle and reversible effects of long‐term BZ use on speed‐dependent tasks in older adults. However, the magnitude of these effects is quite small and may be of little clinical significance in the healthy elderly. Copyright © 2002 John Wiley & Sons, Ltd.
Adverse effects of temazepam in older adults with chronic insomnia
Authors: Morin Charles M. , Bastien Celyne H. , Brink Douglas , Brown Timothy R.
Published: January 2003

Background

Benzodiazepine‐hypnotics are frequently used for treating insomnia in older adults; however, there is little information about adverse effects associated with their usage over several weeks, particularly in this segment of the population.

Objective

This study reports on the incidence of adverse effects of temazepam in older adults with chronic insomnia and examines whether the addition of cognitive‐behaviour therapy (CBT) is associated with less drug used and fewer adverse effects.

Method

Sixty patients with chronic and primary insomnia were randomized to temazepam (n = 20), placebo (n = 20) or temazepam plus CBT (n = 20). Data from the physicians' weekly assessments and patients' sleep diaries were used to evaluate adverse effects, the dose (7.5–30 mg) at which they occurred, and drug use patterns over the 8‐week course of treatment.

Results

The incidence of adverse effects was infrequent, as shown by the low percentages of complaints reported by patients in the temazepam (7.8%), placebo (10.8%) and combination groups (8.3%). The severity of adverse events was mild and decreased over the course of treatment. The maximum dose was reached by 10 patients receiving temazepam, 14 placebo and 7 in the combined treatment. The average nightly dosage used was 20 mg for both the temazepam and placebo groups and 16 mg for the combined condition. Patients receiving temazepam plus CBT used less drugs, with approximately the same incidence of adverse effects.

Conclusion

Temazepam is a safe hypnotic for use by older adults over an 8‐week treatment period. There are few adverse effects and behavioural tolerance to those effects develop over time. The addition of cognitive‐behavioural intervention reduced both the amount of medication used and the incidence of adverse effects, with comparable sleep improvements. Copyright © 2003 John Wiley & Sons, Ltd.
Deguelin suppresses the formation of carcinogen‐induced aberrant crypt foci in the colon of CF‐1 mice
Authors: Murillo Genoveva , Kosmeder Jerome W. , Pezzuto John M. , Mehta Rajendra G.
Published: January 2003

Deguelin [(7aS,BaS)‐13,13a‐dihydro‐9,10‐dimethoxy‐3,3‐dimethyl‐3H‐Bis[1]benzopyrano[3,4‐b:6′,5′‐e]pyran‐7(7aH)‐one], a naturally occurring rotenone, has shown chemopreventive efficacy in several in vivo and in vitro models. In this report, the effectiveness of deguelin at inhibiting the development of AOM‐induced colonic ACF was investigated in CF‐1 mice. Loss of hex activity was assessed as a second biomarker. In an initial experiment, animals were given s.c. injections of AOM (10 mg/kg body weight) once a week for 2 weeks to induce ACF. Deguelin and vehicle (corn oil) were administered i.g. 7 days a week. Treatment was initiated 2 weeks prior to the first dose of carcinogen and continued for the duration of the study. The mean number of ACF for the control group was 29.0 ± 4.3, whereas the mean numbers of ACF in the deguelin groups were 24.8 ± 2.7, 7.2 ± 1.5 and 4.6 ± 1.4 at doses of 2.5, 5.0 and 10.0 mg/kg body weight, respectively. In a similar manner, treatment with deguelin significantly (p < 0.001) suppressed the appearance of hex− crypts in a dose‐dependent manner. In a second study, the ability of deguelin to block the initiation and promotion stages of colon carcinogenesis was investigated. Greatest inhibition was observed when deguelin was administered during the promotional stage (73.3%, p < 0.001). These results demonstrate that deguelin is an efficacious chemopreventive agent against colon carcinogenesis. © 2002 Wiley‐Liss, Inc.
GLUT‐1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: Relationship to pimonidazole binding
Authors: Airley Rachel E. , Loncaster Juliette , Raleigh James A. , Harris Adrian L. , Davidson Susan E. , Hunter Robert D. , West Catharine M.L. , Stratford Ian J.
Published: January 2003

The presence of hypoxia in tumours results in the overexpression of certain genes, which are controlled via the transcription factor HIF‐1. Hypoxic cells are known to be radioresistant and chemoresistant, thus, a reliable surrogate marker of hypoxia is desirable to ensure that treatment may be rationally applied. Recently, the HIF‐1‐regulated proteins Glut‐1 and CAIX were validated as intrinsic markers of hypoxia by comparison with pO2 measured using oxygen electrodes. We compare the expression of Glut‐1 and CAIX with the binding of the bioreductive drug hypoxia marker pimonidazole. Pimonidazole was administered to 42 patients with advanced carcinoma of the cervix, 16 hr before biopsy. Sections of single or multiple biopsies were then immunostained for Glut‐1 and CAIX, and the area of staining scored by eye, using a “field‐by‐field” semi‐quantitative averaging system. Using 1 biopsy only, Glut‐1 (r = 0.54, p = <0.001) correlated with the level of pimonidazole binding, and Glut‐1 and CAIX expression also correlated significantly (r = 0.40, p = <0.009). Thus, our study has shown that HIF‐1 regulated genes have potential for future use as predictors of the malignant changes mediated by hypoxia, and warrant further investigation as indicators of response to cancer therapy. © 2002 Wiley‐Liss, Inc.
Very low concentrations of arsenite suppress poly(ADP‐ribosyl)ation in mammalian cells
Authors: Hartwig Andrea , Pelzer Anke , Asmuss Monika , Bürkle Alexander
Published: January 2003

Arsenite is a naturally occurring environmental pollutant of major concern, since adverse health effects including cancer of skin and internal organs have been attributed to chronic arsenic exposure especially via drinking water. Arsenite is not a significant inducer of point mutations but exerts clastogenic activities and interferes with various DNA repair systems at concentrations in the low micromolar range. Nevertheless, no single DNA repair protein exquisitely sensitive to arsenic has been identified. Here we report that poly(ADP‐ribosyl)ation, which is predominantly mediated by poly(ADP‐ribose) polymerase‐1 (PARP‐1), is inhibited at concentrations as low as 10 nM in cultured HeLa cells, closely matching arsenic concentrations in blood and urine of the general population. Since poly(ADP‐ribosyl)ation is an immediate cellular response to DNA damage, playing a major role in DNA base excision repair and the maintenance of genomic stability, its inhibition by arsenite may add to the risk of cancer formation under low‐exposure conditions. © 2002 Wiley‐Liss, Inc.
Molecular basis of basal cell carcinoma: Analysis of differential gene expression by differential display PCR and expression array
Authors: Welss Thomas , Papoutsaki Marina , Michel Günter , Reifenberger Julia , Chimenti Sergio , Ruzicka Thomas , Abts Harry F.
Published: January 2003

Basal cell carcinoma (BCC) is the most common tumor in the Caucasian population. Although BCC rarely metastasize and cause death, they are problematic due to their destructive growth and the frequent localization on the face. Until now the knowledge of genes differentially expressed in BCC has been incomplete. To elucidate the complex alterations in BCC‐associated gene expression, we took advantage of 2 techniques: the differential display RT‐PCR (DD‐PCR) and the differential hybridization of cDNA arrays. Using DD‐PCR, we showed differential expression of genes known from other biological contexts (e.g., rac, ubiquitin hydrolase), which could now be associated with BCC. In addition, we detected unknown genes possibly contributing to the carcinogenesis of BCC. Of the 588 genes screened by differential hybridization of the Atlas™ human cDNA array, differences in the expression levels of BCC were observed for 10 genes. These data were obtained with RNA probes pooled from several BCC of different donors and were subsequently confirmed by semiquantitative RT‐PCR for Janus protein tyrosine kinase 3 (Jak3), microsomal glutathione S‐transferase 1 (GST 12), teratocarcinoma‐derived growth factor cripto, glutaredoxin and the monocyte chemoattractant protein 1 (MCP‐1) in 10 individual BCC specimens, 2 squamous cell carcinoma (SCC), the cell line HaCaT and cultured normal human keratinocytes (NHK) in comparison to normal skin. These genes are candidates from gene families with known association to tumors, but they have not been reported in the carcinogenesis of BCC yet. In summary, both approaches allow the detection of differentially expressed genes possibly involved in the carcinogenesis of BCC. © 2002 Wiley‐Liss, Inc.
Prognostic value of tumor‐infiltrating dendritic cells expressing CD83 in human breast carcinomas
Authors: Iwamoto Mitsuhiko , Shinohara Hisashi , Miyamoto Akiko , Okuzawa Masaaki , Mabuchi Hideaki , Nohara Takehiro , Gon Goki , Toyoda Masao , Tanigawa Nobuhiko
Published: January 2003

DCs are the most potent antigen‐presenting cells that play a major role in initiating the antitumor immune response. Although the clinical significance of TIDCs has been investigated in a variety of human cancers, few studies have focused on the in situ maturation status of DCs. We have analyzed the maturation‐specific significance of TIDCs in the prognosis of patients with breast carcinoma. We evaluated 130 breast carcinomas for the presence of TIDCs using immunohistochemistry with an anti‐CD1a antibody for immature DCs and an anti‐CD83 antibody for mature DCs. Intratumoral expression of immunosuppressive cytokines was also examined. All samples contained CD1a+ TIDCs, and 82 (63.1%) samples contained CD83+ TIDCs. The number of CD83+ TIDCs was inversely correlated with lymph node metastasis and with tissue expression of VEGF and TGF‐β, whereas the number of CD1a+ TIDCs was not. Kaplan‐Meier analysis (log rank statistics) revealed a significant association of increasing number of CD83+ TIDCs with longer relapse‐free (p = 0.002) and overall (p < 0.001) survival. Furthermore, among patients with lymph node metastasis, the survival rate of those with larger numbers of CD83+ TIDCs was significantly better than that of patients with fewer CD83+ TIDCs. Multivariate analysis revealed that CD83+ TIDCs had independent prognostic relevance in breast carcinomas. The infiltration of tumors by mature DCs expressing CD83 may be of great importance in initiating the primary antitumor immune response and is confirmed as an independent, immunologic prognostic parameter for survival in patients with breast cancer. © 2002 Wiley‐Liss, Inc.
Immune enhancement of nitroreductase‐induced cytotoxicity: Studies using a bicistronic adenovirus vector
Authors: Green Nicola K. , McNeish Iain A. , Doshi Rajeev , Searle Peter F. , Kerr David J. , Young Lawrence S.
Published: January 2003

The nitroreductase (NR)/CB1954 enzyme prodrug system has given promising results in preclinical studies and is currently being assessed in phase I clinical trials. It is well established that there is an immune component to the bystander effect observed with other systems such as thymidine kinase and cytosine deaminase; however, such an effect has not previously been described using NR. We have preliminary data suggesting an immune bystander effect with NR to further examine these effects and their potential enhancement by cytokines, an adenoviral vector containing CMV‐NR, an internal ribosome entry site (IRES) and the gene for murine GM‐CSF (mGM‐CSF) was constructed. The NR‐GM‐CSF virus was validated in 2 experimental models and demonstrated increased therapeutic efficacy in the MC26 murine colorectal tumour model. These data illustrate that the combination of suicide gene therapy using NR and CB1954 with immune stimulation via GM‐CSF gives an improved response compared to either modality alone and suggests that the immune component of this response may be beneficial in combating unresectable, metastatic disease and preventing tumour recurrence. © 2002 Wiley‐Liss, Inc.
Effects of E‐cadherin transfection on gene expression of a gallbladder carcinoma cell line: Repression of MTS1/S100A4 gene expression
Authors: Kohya Naohiko , Kitajima Yoshihiko , Jiao Wan , Miyazaki Kohji
Published: January 2003

E‐cadherin is important in cell‐to‐cell adhesion and controls cell polarity and tissue morphology. Loss of E‐cadherin expression occurs in various human tumors and is the first step in cancer invasion and metastasis. We demonstrate that the exogenous expression of E‐cadherin transfected into G‐415 GB cells not only increases cell‐to‐cell adhesion but also reduces in vitro cell proliferation, motility and invasion. Our aim was to determine what genes are most affected by the exogenous expression of E‐cadherin in GB cancer cells. We analyzed gene expression pertaining to cell proliferation, motility and invasion. Conventional RT‐PCR was performed for these genes; quantitative RT‐PCR was carried out on genes exhibiting altered expression. Conventional RT‐PCR revealed that E‐cadherin transfection suppressed expression of mts1 mRNA and increased that of c‐myc and MT1‐MMP. In quantitative RT‐PCR analysis, levels of c‐myc and MT1‐MMP mRNA were elevated by to 2.56‐ and 2.22‐fold, respectively, in the E‐cadherin transfectant, whereas mts‐1 was 7.14‐fold suppressed compared to parental cells. These results indicated that expression of mts1 mRNA was most affected by E‐cadherin transfection. Immunocytochemical analysis of transfectant and parental cells demonstrated an inverse correlation in E‐cadherin and mts1 expression. Immunohistochemical analysis of 37 GB cancer specimens confirmed this observation in vivo. Loss of E‐cadherin expression followed by expression of the mts1 gene may be an important event for increasing cell proliferation, motility and invasion activity in the progression of GB cancer. © 2002 Wiley‐Liss, Inc.
Sodium selenite, dietary micronutrient, prevents the lymphocyte DNA damage induced by N‐nitrosodiethylamine and phenobarbital promoted experimental hepatocarcinogenesis
Authors: Thirunavukkarasu C. , Sakthisekaran D.
Published: January 2003

Selenium (Se), a micronutrient, has a long history in chemoprevention of mammary and colon cancers in rodent models. Se is a current clinical trial, having shown promise in prevention of prostate and other human cancers. The mechanisms involved in the in vivo anti‐carcinogenic activity of Se remain to be elucidated. In the present study, we examined the effect of sodium selenite supplementation in lymphocytes, obtained from hepatoma bearing rats on DNA damage in correlation with oxidative stress. In addition, this study examined the supplementation of Se at 4‐ppm levels in the form of sodium selenite either before initiation or during initiation and/or promotion phase's increases lymphocyte Se concentrations. This in turn improves lymphocyte resistance to oxidative stress and protection against the lymphocytes DNA damage. Supplementation of Se increased lymphocyte Se concentration and reduced lymphocytes DNA damage as determined by single cell gel electrophoresis. The enzymatic antioxidants such as superoxide dismutase, glutathione peroxidase, and catalase were found to be decreased while the thiobarbituric acid reactive substances level was increased in the lymphocytes of hepatoma bearing rats. Furthermore, the reactive oxygen species such as superoxide radicals and hydroxyl radicals were also found to be high in lymphocytes. Our present results explain the understanding of unique association between anti‐peroxidative effect of Se and ultimately the capability of Se to prevent cancer. © 2002 Wiley‐Liss, Inc.
Nuclear matrix localization of high mobility group protein I(Y) in a transgenic mouse model for prostate cancer
Authors: Leman Eddy S. , Madigan Michael C. , Brünagel Gisela , Takaha Natsuki , Coffey Donald S. , Getzenberg Robert H.
Published: January 2003

Nuclear shape and the underlying nuclear structure, the nuclear matrix in cancer cells. Since the NM composition is considered to maintain nuclear shape and architecture, nuclear matrix proteins (NMPs) may be involved in transformation. Our laboratory has recently characterized a subset of NMPs that are associated with prostate cancer development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. One of the identified NMPs, E3E, has a similar molecular weight (22 kDa) with a protein known as HMGI(Y). HMGI(Y) belongs to a group of non‐histone and chromatin‐associated proteins, high‐mobility‐group (HMG) proteins, and it has been shown to associate with the NM. HMGI(Y) has been reported to be elevated in different types of cancer including prostate cancer. In this study, we examined the expression of HMGI(Y) protein in the NMP composition of the TRAMP model during the progression from normal to neoplasia. The expression of HMGI(Y) in the NMP extracts of three prostatic epithelial cell lines derived from a 32‐week TRAMP mouse: TRAMP‐C1, TRAMP‐C2, and TRAMP‐C3 was also examined. Using both one‐dimensional and high‐resolution two‐dimensional immunoblot analyses, we found that: (i) HMGI(Y) is a nuclear matrix protein expressed as two protein bands with MW of 22–24 kDa and (ii) HMGI(Y) expression is correlated with neoplastic and malignant properties in late stage TRAMP prostate tumors. Overall, these findings support the evidence that HMGI(Y) can be utilized as a marker and prognostic tool for prostate cancer. © 2002 Wiley‐Liss, Inc.
Differential regulation of Notch signal transduction in leukaemia and lymphoma cells in culture
Authors: Chiaramonte Raffaella , Calzavara Elisabetta , Balordi Francesca , Sabbadini Marta , Capello Daniela , Gaidano Gianluca , Serra Anna , Comi Paola , Sherbet G. V.
Published: January 2003

The transduction of Notch signal plays an intricate role in cell differentiation and pathogenesis of haematological malignancies as well as in certain congenital conditions. We found no genomic changes in either gene in 34 leukaemic samples and 25 leukaemia and lymphoma cell lines. The functionality of Notch signalling was tested using HES1 gene activation. We show that Notch signalling is differentially regulated in T‐acute lymphoblastic leukaemia (ALL) and B‐lymphoma cells. The Notch pathway is intact in a majority of B‐lymphoma cell lines, but EBNA2, which mimics notch function, can occasionally activate the pathway. In contrast, the Notch pathway is constitutively active in T‐ALL. This is the first demonstration of a distinction between B‐lymphomas and T‐cell leukaemias in the functioning of the Notch‐signalling pathway. This might be related to their pathogenesis. © 2002 Wiley‐Liss, Inc.
Membrane receptors for steroid hormones: Signal transduction and physiological significance
Authors: Nemere Ilka , Pietras Richard J. , Blackmore Peter F.
Published: January 2003

Membrane receptors for steroid hormones affect signaling pathways that modulate nuclear function, influence neuronal activity, ion flow, and the circulatory system. Indeed, ‘new’ steroid hormones have been identified by their interaction with membrane‐initiated signaling systems. A brief summary of the FASEB Summer Research Conference devoted to these topics is presented in this mini‐review. In addition, attendees of the meeting propose introduction of the following terminology: membrane‐initiated steroid signaling (MISS) and nuclear‐initiated steroid signaling (NISS) to replace more inaccurate terms in current use. © 2002 Wiley‐Liss, Inc.
Effect of activation temperature on pore development in activated carbon produced from palm shell
Authors: Wan Daud Wan Mohd Ashri , Ali Wan Shabuddin Wan , Sulaiman Mohd Zaki
Published: January 2003

A series of experiments were conducted to investigate the effect of activation temperature on pore development of activated carbon produced from palm shell. Activation of the samples was carried out at 800, 850 and 900 °C for different durations ranging from 10 to 180 min. The samples were characterized using N2 adsorption for evaluation of micropores and the mercury intrusion technique for mesopore and macropore analysis. Within the range of activation temperatures studied, high burn‐off products derived from high activation temperatures tend to have larger micropore development. However, an increase in the activation temperature has no remarkable effect on mesopore and macropore development.

© 2002 Society of Chemical Industry
Mezen Bay—a key area for understanding Weichselian glaciations in northern Russia
Authors: Kjær Kurt H. , Demidov Igor N. , Larsen Eiliv , Murray Andrew , Nielsen Jan K.
Published: January 2003

Sediment successions in coastal cliffs around Mezen Bay, southeastern White Sea, record an unusually detailed history of former glaciations, interstadial marine and fluvial events from the Weichselian. A regional glaciation model for the Weichselian is based on new data from the Mezen Bay area and previously published data from adjacent areas. Following the Mikulinian (Eemian) interglacial a shelf‐centred glaciation in the Kara Sea is reflected in proglacial conditions at 100–90 ka. A local ice‐cap over the Timan ridge existed between 75 and 65 ka. Renewed glaciation in the Kara Sea spread southwestwards around 60 ka only, interrupted by a marine inundation, before it advanced to its maximum position at about 55–50 ka. After a prolonged ice‐free period, the Scandinavian ice‐sheet invaded the area from the west and terminated east of Mezen Bay about 17 ka. The previously published evidence of a large ice‐dammed lake in the central Arkhangelsk region, Lake Komi, finds no support in this study. Copyright © 2003 John Wiley & Sons, Ltd.
Index sets for ω‐languages
Authors: Czenzer Douglas , Remmel Jeffrey B.
Published: January 2003

An ω‐language is a set of infinite sequences (words) on a countable language, and corresponds to a set of real numbers in a natural way. Languages may be described by logical formulas in the arithmetical hierarchy and also may be described as the set of words accepted by some type of automata or Turing machine. Certain families of languages, such as the $ \Sigma ^0 _2 $ languages, may enumerated as P0, P1, … and then an index set associated to a given property R (such as finiteness) of languages is just the set of e such that Pe has the property. The complexity of index sets for 7 types of languages is determined for various properties related to the size of the language.
Approximate decidability in euclidean spaces
Authors: Hemmerling Armin
Published: January 2003

We study concepts of decidability (recursivity) for subsets of Euclidean spaces ℝk within the framework of approximate computability (type two theory of effectivity). A new notion of approximate decidability is proposed and discussed in some detail. It is an effective variant of F. Hausdorff's concept of resolvable sets, and it modifies and generalizes notions of recursivity known from computable analysis, formerly used for open or closed sets only, to more general types of sets. Approximate decidability of sets can equivalently be expressed by computability of the characteristic functions by means of appropriately working oracle Turing machines. The notion fulfills some natural requirements and is hereditary under canonical embeddings of sets into spaces of higher dimensions. However, it is not closed under binary union or intersection of sets. We also show how the framework of resolvability and approximate decidability can be applied to investigate concepts of reducibility for subsets of Euclidean spaces.
Expansions of ordered fields without definable gaps
Authors: Eivazloo Jafar S. , Moniri Mojtaba
Published: January 2003

In this paper we are concerned with definably, with or without parameters, (Dedekind) complete expansions of ordered fields, i. e. those with no definable gaps. We present several axiomatizations, like being definably connected, in each of the two cases. As a corollary, when parameters are allowed, expansions of ordered fields are o‐minimal if and only if all their definable subsets are finite disjoint unions of definably connected (definable) subsets. We pay attention to how simply (in terms of the quantifier complexity and/or usage of parameters) a definable gap in an expansion is so. Next we prove that over parametrically definably complete expansions of ordered fields, all one‐to‐one definable (with parameters) continuous functions are monotone and open. Moreover, in both parameter and parameter‐free cases again, definably complete expansions of ordered fields satisfy definable versions of the Heine‐Borel and Extreme Value theorems and also Bounded Intersection Property for definable families of closed bounded subsets.
The shortest definition of a number in Peano arithmetic
Authors: Roy Dev K.
Published: January 2003

The shortest definition of a number by a first order formula with one free variable, where the notion of a formula defining a number extends a notion used by Boolos in a proof of the Incompleteness Theorem, is shown to be non computable. This is followed by an examination of the complexity of sets associated with this function.
Strongly maximal subgroups determined by elements in interstices
Authors: Bigorajska Teresa
Published: January 2003

Continuing the earlier research in [1] and [4] we work out a class of interstices in countable arithmetically saturated models of PA in which selective types are realized and a class of interstices in which 2‐indiscernible types are realized (and hence, there exist elements whose stabilizers are strongly maximal)
Blue‐Light‐Emitting Conjugated Polymers Derived From 2,7‐Carbazoles
Authors: Morin Jean‐François , Boudreault Pierre‐Luc , Leclerc Mario
Published: January 2003

Blue‐light‐emitting 2,7‐carbazole‐based conjugated copolymers have been prepared by Yamamoto or Suzuki cross‐coupling reactions. By introducing highly substituted aromatic comonomers, fully soluble high‐molecular‐weight copolymers have been obtained. Moreover, these amorphous polymeric materials exhibit good thermal stability and interesting redox properties. All these features make these new conjugated polymers highly promising for the development of single‐polymer‐layer blue‐light‐emitting diodes.

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Protein expression levels of the Src activating protein AFAP are developmentally regulated in brain
Authors: Clump David A. , Clem Roger , Qian Yong , Guappone‐Koay Anne , Berrebi Albert S. , Flynn Daniel C.
Published: January 2003

The Src family of nonreceptor tyrosine kinases plays an important role in modulating signals that affect growth cone extension, neuronal differentiation, and brain development. Recent reports indicate that the Src SH2/SH3 binding partner AFAP‐110 has the capacity to modulate actin filament integrity as a cSrc activating protein and as an actin filament bundling protein. Both AFAP‐110 and a brain specific isoform called AFAP‐120 (collectively referred to as AFAP) exist at high levels in chick embryo brain. We sought to identify the localization of AFAP in mouse brain in order to identify its expression pattern and potential role as a cellular modulator of Src family kinase activity and actin filament integrity in the brain. In E16 mouse embryos, AFAP expression levels were very high and concentrated in the olfactory bulb, cortex, forebrain, cerebellum, and various peripheral sensory structures. In P3 mouse pups, overall expression was reduced compared to E16 embryos, and AFAP was found primarily in olfactory bulb, cortex, and cerebellum. AFAP expression levels were significantly reduced in adult mice, with high expression levels only detected in the olfactory bulb. Western blot analysis indicated that concentrated expression of AFAP correlates well with the AFAP‐120 isoform, which appears to be a splice variant of AFAP‐110. As the expression pattern of AFAP overlaps with the reported expression patterns of cSrc and Fyn, we hypothesize that AFAP is positioned to modulate signal transduction cascades that direct activation of these nonreceptor tyrosine kinases and concomitant cellular changes that occur in actin filaments during brain development. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 473–485, 2003
PDGF and FGF2 regulate oligodendrocyte progenitor responses to demyelination
Authors: Frost Emma E. , Nielsen Joseph A. , Le Tuan Q. , Armstrong Regina C.
Published: January 2003

Acute demyelination of adult CNS, resulting from trauma or disease, is initially followed by remyelination. However, chronic lesions with subsequent functional impairment result from eventual failure of the remyelination process, as seen in multiple sclerosis. Studies using animal models of successful remyelination delineate a progression of events facilitating remyelination. A universal feature of this repair process is extensive proliferation of oligodendrocyte progenitor cells (OPs) in response to demyelination. To investigate signals that regulate OP proliferation in response to demyelination we used murine hepatitis virus‐A59 (MHV‐A59) infection of adult mice to induce focal demyelination throughout the spinal cord followed by spontaneous remyelination. We cultured glial cells directly from demyelinating and remyelinating spinal cords using conditions that maintain the dramatically enhanced OP proliferative response prior to CNS remyelination. We identify PDGF and FGF2 as significant mitogens regulating this proliferative response. Furthermore, we demonstrate endogenous PDGF and FGF2 activity in these glial cultures isolated from demyelinated CNS tissue. These findings correlate well with our previous demonstration of increased in vivo expression of PDGF and FGF2 ligand and corresponding receptors in MHV‐A59 lesions. Together these studies support the potential of these pathways to function in vivo as critical factors in regulating remyelination. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 457–472, 2003
Ethological methods to develop nursing knowledge
Authors: Warnock Fay F. , Allen Marion
Published: January 2003

Researchers from various fields use ethological methods to systematically observe, describe, and measure animal and human nonverbal behavior. The purpose of this article is to argue that their application in nursing will benefit development of descriptive‐level knowledge about complex behavioral phenomena. To advance the argument for applying these methods in nursing, we examine the compatibility of the philosophical assumptions underlying ethology with nursing, assess if ethology can help nursing achieve some of its aims, and determine the benefits of using ethology when observation of a phenomenon is required. Neonatal pain is used to illustrate how ethology can be used to develop descriptive‐level nursing knowledge and midrange theory. © 2003 Wiley Periodicals, Inc. Res Nurs Health 26:74–84, 2003