bluuebunny/crossref_metadata_2025 huggingface dataset:
Glia cell number modulates sensitivity to MPTP in mice
Authors: Smeyne Michelle , Jiao Yun , Shepherd Kennie R. , Smeyne Richard J.
Published: May 2005

Free radical damage has been shown to play a significant role in the pathogenesis of a number of neurodegenerative diseases including Parkinson's disease. One model of experimental parkinsonism is the loss of substantia nigra cells following administration of MPTP. Previously, it has been shown that a number of inbred strains of mice have differential responses to this toxin, and this difference is dependent on glial cells. In this study, the number of glial cells in the substantia nigra pars compacta of C57Bl/6J (MPTP‐sensitive) and Swiss Webster (MPTP‐resistant) strains of mice was examined. The C57Bl/6J mice have an approximately 50% lower number of GFAP+ and S‐100β glial cells than the Swiss Webster mice. C57Bl/6J mice have a 25% increased number of resident nonactivated microglial cells. To determine whether this difference in cell number has functional significance, we used an in vitro SN culture system that allowed us to manipulate the number of glial cells. When C57Bl/6 neurons were grown on a glial mat plated with twice the number of cells, we were able to rescue the MPTP‐sensitive neurons from toxin‐induced cell death. This suggests that the number of glial cells in the SNpc may be an important factor in the survival of dopaminergic neurons following exposure to xenobiotics. © 2005 Wiley‐Liss, Inc.
Double‐stranded RNA signals antiviral and inflammatory programs and dysfunctional glutamate transport in TLR3‐expressing astrocytes
Authors: Scumpia Philip O. , Kelly Kindra M. , Reeves Westley H. , Stevens Bruce R.
Published: May 2005

Astrocyte inflammation, reactive oxygen species (ROS) formation, and dysfunction form a common denominator shared by all the major neurodegenerative disorders. Viral infections are emerging as important events in the etiology of CNS damage involving astrocytes, but molecular understanding is incomplete. Double‐stranded RNA (dsRNA) is a byproduct of viral replication and serves as the signature molecule for viral infection via Toll‐like receptor 3 (TLR3) largely restricted to circulating peripheral dendritic cells. However, astrocytes are strategically located at the blood‐brain barrier (BBB) and throughout brain tissues, making these cells ideal candidates as innate immunity sentinels within the CNS. We hypothesized that extracellular dsRNA, mimicked by polyinosinic‐polycytidylic acid (Poly(I:C); PIC), initiates signaling of the double‐edged sword of antiviral plus pathophysiological events in astrocytes. Using Western blot analysis and real‐time qPCR, we determined that neonatal rat astrocyte cultures constitutively express TLR3 mRNA and protein, and that PIC dsRNA induced phosphorylation of eIF2α, as well as mRNA type I interferon (α/β IFN)‐response genes Mx1, PKR, and TLR3. Astrocyte TLR3 protein was downregulated after PIC treatment, however. PIC signaled degradation of IκBα with the consequence of upregulating iNOS, TNF‐α, and IL‐1β mRNAs and proteins. In addition to antiviral protection events, dsRNA induced astrocyte dysfunction, evidenced by inhibiting EAAT1/GLAST transporter gene expression and attenuating L‐glutamate uptake via sodium‐dependent transport system X, as well as inducing cytotoxicity. Anti‐TLR3 blocking antibody attenuated PIC upregulation of TNF‐α mRNA and iNOS activity. Extracellular PIC‐induced events were prevented by 2‐aminopurine, implicating PKR as an important downstream player in astrocyte dsRNA sensing pathways. The effects of plasma membrane impermeable poly(I:C) were dose‐dependent (0–50 μM). In concert, these data provide evidence that dsRNA/TLR3‐activated astrocytes initiate a battery of rapid innate pathogen‐associated molecular pattern (PAMP) immune responses that are important for mounting antiviral defense in the CNS, yet also lead to pathophysiological events associated with the glutamate neurotoxicity of neurodegenerative diseases. © 2005 Wiley‐Liss, Inc.
Caregiving burden and psychiatric morbidity in spouses of persons with mild cognitive impairment
Authors: Garand Linda , Amanda Dew Mary , Eazor Linda R. , DeKosky Steven T. , Reynolds Charles F.
Published: May 2005

Background

While the deleterious psychosocial and mental health effects of dementia caregiving are firmly established, very little is known about the burdens or psychiatric outcomes of providing care to a spouse with less severe cognitive impairment, such as mild cognitive impairment (MCI). We characterized the nature and level of caregiver burden and psychiatric morbidity in spouses of persons diagnosed with MCI.

Methods

Interview assessments were completed on a cohort of 27 spouses of persons with a recent diagnosis of MCI. Patient medical records were reviewed to collect information regarding the MCI patient's medical history.

Results

Respondents endorsed elevated levels of both task‐related responsibilities and subjective caregiver burden. Depression and anxiety symptom levels also showed some elevations. Measures of caregiver burden were significantly associated with depression and anxiety levels. In particular, even after controlling for demographic risk factors for distress, nursing task burden was correlated with elevated depressive symptoms, and greater lifestyle constraints were correlated with higher anxiety levels.

Conclusions

Although caregiver burden and psychiatric morbidity levels were lower than those typically observed in family dementia caregiving samples, our findings suggest that MCI caregivers have already begun to experience distress in association with elevated caregiving burden. These individuals may be ideal targets for selective preventive interventions to maximize their psychological well‐being as caregiving burdens related to their spouses' cognitive impairment increase. Copyright © 2005 John Wiley & Sons, Ltd.
Why caregivers of people with dementia and memory loss don't use services
Authors: Brodaty Henry , Thomson Cathy , Thompson Claire , Fine Michael
Published: May 2005

Objectives

To develop a typography of the characteristics of caregivers of community dwelling people with dementia or memory loss who do not use services and empirically investigate the reasons for service non‐use.

Method

The findings of a literature review were used to develop a typography of caregivers' non‐use of services. This typography was applied to a sample of community‐based caregivers.

Results

One in three caregivers were using no services and one in four only one service. Despite considerable proportions reporting low levels of life satisfaction and high levels of overload and resentment the main reasons caregivers gave for not using services were that they did not consider they needed the services. Other reasons for service non‐use included care recipient reluctance to use services, lack of knowledge of services or being in the process of applying for services. Service availability or affordability were not identified as major impediments to service use. Presence of a physical disability and contact with a social worker were associated with service use.

Conclusions

Caregivers of people with dementia incur significant strain and have substantial need for a variety of services. Nevertheless many caregivers were not using support services, mainly because of perceived lack of need or lack of awareness. Better public promotion of services, destigmatising dementia and encouraging referrals from health professionals could help overcome the barriers to service use. Copyright © 2005 John Wiley & Sons, Ltd.
Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo‐controlled trial
Authors: Feldman Howard , Gauthier Serge , Hecker Jane , Vellas Bruno , Xu Yikang , Ieni John R. , Schwam Elias M.
Published: May 2005

Background

There have been very limited investigations of cholinesterase inhibitor therapy in more advanced stages of Alzheimer's disease (AD). The efficacy and safety of donepezil were evaluated in post hoc analyses of a subgroup of patients with more severe AD (standardized Mini‐Mental State Examination [sMMSE] score 5–12) within a randomized, placebo‐controlled trial in moderate to severe AD (MSAD study). Additional analyses examined whether donepezil's treatment effects were consistent across the full range of baseline AD severity studied (sMMSE score 5–17).

Methods

Patients with moderate to severe AD (n = 290) who were living in the community or in assisted living facilities received donepezil or placebo for 24 weeks; n = 145 in the more severe AD subgroup. The primary outcome measure was the Clinician's Interview‐Based Impression of Change (CIBIC‐plus) with secondary outcomes including the sMMSE, Severe Impairment Battery, Neuropsychiatric Inventory, and Disability Assessment for Dementia. Analysis of Variance and Analysis of Covariance models tested for treatment×disease severity interaction in the full MSAD study sample.

Results

CIBIC‐plus scores for donepezil patients were significantly improved compared with placebo for each time‐point, with a 0.70 mean treatment difference at Week 24 last observation carried forward (LOCF; p = 0.0002). Significant differences favoring donepezil were noted at Week 24 LOCF for all secondary measures. There were no treatment×severity interactions for any of the efficacy measures.

Conclusions

In this analysis, donepezil had significant benefits over placebo on global, cognitive, functional, and behavioral measures in a subgroup of patients with more severe AD. Furthermore, the treatment effects of donepezil were not driven by a particular stratum within the moderate to severe dementia range. Copyright © 2005 John Wiley & Sons, Ltd.
A calcium phosphate‐based gene delivery system
Authors: Fu Huihua , Hu Yunhua , McNelis Tim , Hollinger Jeffrey O.
Published: May 2005

Although nonviral vectors have lower transfection efficiency than viral vectors, the excellent safety profile of nonviral vectors is appealing for gene therapy. An efficient, simple nonviral vector gene delivery system has been designed that includes plasmid DNA–calcium phosphate precipitates (pDNA‐CaP) and porous collagen spheres (Cultispheres™). The hypothesis for this study was the pDNA‐CaP would achieve efficient plasmid DNA transfection and the porous collagen spheres would provide a suitable delivery carrier system for three‐dimensional (3D) administration. To test the hypothesis, plasmid DNA including the LacZ reporter gene encoding β‐galactosidase was precipitated with CaP to form particles of compacted LacZ‐CaP and delivered directly or by Cultispheres™ to cells in vitro. The transfection efficiency was determined by β‐galactosidase gene expression. Results indicated that pLacZ‐CaP promoted 25–84% of transfection efficiency in a broad cell line spectrum and in flexible experimental conditions. Maximum transfection efficiency was achieved by having mostly nano‐sized partles (50–200 nm in diameter) of pDNA‐CaP precipitates. Seeding density of 0.7–4 × 104 cells/cm2 provided sufficient transfection efficiency, and storage of pDNA‐CaP at 4°C was most efficient to preserve transfection efficacy for up to 3 days. The pDNA‐CaP worked well in the presence of serum and serum‐free conditions and was less cytotoxic than the liposomes. Cultispheres™ carrying plasmid LacZ‐CaP was an effective 3D system for gene delivery. The technique described here is a simple and safe procedure to deliver genes, and may have application to regenerate bone and other tissues. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
MT1‐MMP: A potent modifier of pericellular microenvironment
Authors: Itoh Yoshifumi , Seiki Motoharu
Published: May 2005

Cells are regulated by many different means, and there is more and more evidence emerging that changes in the microenvironment greatly affect cell function. MT1‐MMP is a type I transmembrane proteinase which participates in pericellular proteolysis of extracellular matrix (ECM) macromolecules. The enzyme is cellular collagenase essential for skeletal development, cancer invasion, growth, and angiogenesis. MT1‐MMP promotes cell invasion and motility by pericellular ECM degradation, shedding of CD44 and syndecan1, and by activating ERK. Thus MT1‐MMP is one of the factors that influence the cellular microenvironment and thereby affect cell‐signaling pathways and eventually alters cellular behavior. As a proteinase, MT1‐MMP is regulated by inhibitors, but it also requires formation of a homo‐oligomer complex, localization to migration front of the cells, and internalization to become a “functionally active” cell function modifier. Developing new means to inhibit “functional activity” of MT1‐MMP may be a new direction to establish treatments for the diseases that MT1‐MMP mediates such as cancer and rheumatoid arthritis. © 2005 Wiley‐Liss, Inc.
MEK hyperphosphorylation coincides with cell cycle shut down of cultured smooth muscle cells
Authors: Vogel Sabina , Kubin Thomas , von der Ahe Dietmar , Deindl Elisabeth , Schaper Wolfgang , Zimmermann René
Published: May 2005

Smooth muscle cells (SMCs) form the backbone of arteries and their proliferation hallmarks collateral vessel growth, a process termed arteriogenesis, as well as pathogenic responses such as restenosis. Since signaling pathways in SMCs are the main targets for therapeutic interventions, we aimed to determine how and to what extent the activation of the ubiquitous MEK–ERK signaling pathway correlates with important in vivo phenomena such as dedifferentiation, nuclear activation and proliferation of SMCs. Specificity of this pathway was monitored using MEK inhibitors UO126 and PD98059 in platelet derived growth factor‐AB (PDGF‐AB)‐ and fibroblast growth factor‐2 (FGF‐2)‐stimulated SMCs. PDGF‐AB induced a rapid MEK activation followed by phosphorylation of the MEK substrates ERK1/2 while FGF‐2 showed a less pronounced and delayed activation. Both growth factors triggered a marked phosphorylation of c‐Myc and expression of Egr1. Pretreatment with MEK inhibitors suppressed the activation of the ERK cascade, abolished the down‐regulation of desmin and led to cell cycle arrest. However, the reversibility of p27Kip1 down‐regulation by UO126 was mainly observed after PDGF‐AB stimulation, indicating MEK independent p27Kip1 down‐regulation by FGF‐2. Surprisingly, treatment of SMCs with UO126 or PD98059 increased the level of MEK phosphorylation in a dose dependent manner at serine residues 217/221 in the presence as well as in the absence of both growth factors. Our results strongly imply that depending on the environmental context phosphorylation of serines 217/221 serves as an “on” as well as an “off ” switch. © 2005 Wiley‐Liss, Inc.
Covalent immobilization of naringinase for the transformation of a flavonoid
Authors: Puri Munish , Kaur Harsimran , Kennedy John F
Published: May 2005

Naringinase (EC 3.2.1.40) from Penicillium sp was immobilized by covalent binding to woodchips to improve its catalytic activity. The immobilization of naringinase on glutaraldehyde‐coated woodchips (600 mg woodchips, 10 U naringinase, 45 °C, pH 4.0 and 12h) through 1% glutaraldehyde cross‐linking was optimized. The pH–activity curve of the immobilized enzyme shifted toward a lower pH compared with that of the soluble enzyme. The immobilization caused a marked increase in thermal stability of the enzyme. The immobilized naringinase was stable during storage at 4 °C. No loss of activity was observed when the immobilized enzyme was used for seven consecutive cycles of operations. The efficiency of immobilization was 120%, while soluble naringinase afforded 82% efficacy for the hydrolysis of standard naringin under optimal conditions. Its applicability for debittering kinnow mandarin juice afforded 76% debittering efficiency. Copyright © 2005 Society of Chemical Industry
Disinfection of recycled red‐meat‐processing wastewater by ozone
Authors: Wu Jiangning , Doan Huu
Published: May 2005

Ozonation of a real red‐meat‐processing wastewater was conducted in a semi‐batch reactor to explore the possibility of the water reuse. The experimental results revealed that ozone was very effective in disinfection of the red‐meat‐processing wastewater. After 8 min of ozonation with an applied ozone dose of 23.09 mg min−1 liter−1 of wastewater, 99% of aerobic bacteria, total coliforms and Escherichia coli were inactivated. Empirical models were developed to predict the microbial inactivation efficacy of ozone from the CT values for the real red‐meat‐processing wastewater. A correlation was also derived to estimate the CT values from the applied ozone dose and the ozone contact time. The results also revealed that under the ozonation condition for 99% inactivation of aerobic bacteria, total coliforms and E coli, the decrease in the chemical oxygen demand and the 5‐day biological oxygen demand of the wastewater were 10.7% and 23.6%, respectively. However, ozonation under this condition neither improved the light transmission nor reduced the total suspended solids (TSS) despite of the decolorization of the wastewater after ozonation. Copyright © 2005 Society of Chemical Industry
Optimization of lactic acid production from whey by L casei NRRL B‐441 immobilized in chitosan stabilized Ca‐alginate beads
Authors: Göksungur Y , Gündüz M , Harsa Ş
Published: May 2005

The production of lactic acid from whey by Lactobacillus casei NRRL B‐441 immobilized in chitosan‐stabilized Ca‐alginate beads was investigated. Higher lactic acid production and lower cell leakage were observed with alginate–chitosan beads compared with Ca‐alginate beads. The highest lactic acid concentration (131.2 g dm−3) was obtained with cells entrapped in 1.3–1.7 mm alginate–chitosan beads prepared from 2% (w/v) Na‐alginate. The gel beads produced lactic acid for five consecutive batch fermentations without marked activity loss and deformation. Response surface methodology was used to investigate the effects of three fermentation parameters (initial sugar, yeast extract and calcium carbonate concentrations) on the concentration of lactic acid. Results of the statistical analysis showed that the fit of the model was good in all cases. Initial sugar, yeast extract and calcium carbonate concentrations had a strong linear effect on lactic acid production. The maximum lactic acid concentration of 136.3 g dm−3 was obtained at the optimum concentrations of process variables (initial sugar 147.35 g dm−3, yeast extract 28.81 g dm−3, CaCO3 97.55 g dm−3). These values were obtained by fitting of the experimental data to the model equation. The response surface methodology was found to be useful in optimizing and determining the interactions among process variables in lactic acid production using alginate–chitosan‐immobilized cells. Copyright © 2005 Society of Chemical Industry
Bioleaching of heavy metals from dewatered sludge by Acidithiobacillus ferrooxidans
Authors: Kim In S , Lee Jong‐Un , Jang Am
Published: May 2005

The feasibility of bioleaching for removal of heavy metals from dewatered sewage sludge using an iron‐oxidizing bacterium Acidithiobacillus ferrooxidans was investigated. The influence of seven process parameters including cell adaptation, total amount and particle size of the sludge, initial concentrations of Fe2+ and At ferrooxidans, and addition of inorganic nutrients and sulfur were evaluated in terms of the solubilization of Zn, Cu and Cr. When sludge‐adapted cells, addition of inorganic nutrients and lower sludge content were involved, higher yields of metal extraction were obtained. However, higher initial concentrations of At ferrooxidans and Fe2+, fine particle size of the sludge and S addition did not improve the metals' solubilization during an experimental period of 7 days. As a result of a long‐term (40 days) bioleaching experiment, 42% of Zn (1300–1648 mg kg−1), 39% of Cu (613–774 mg kg−1) and 10% of Cr (37–44 mg kg−1) in the sludge were leached into the solution. The results indicate that a bioleaching process conducted under operationally optimal conditions can be effectively employed for the removal of heavy metals from sewage sludge before land application. Copyright © 2005 Society of Chemical Industry
Cinnamic ester of D‐sorbitol for immobilization of mushroom tyrosinase
Authors: Marín‐Zamora María Elisa , Rojas‐Melgarejo Francisco , García‐Cánovas Francisco , García‐Ruiz Pedro Antonio
Published: May 2005

Mushroom tyrosinase was immobilized by adsorption onto the totally cinnamoylated derivative of D‐sorbitol. The polymerization and cross‐linking of the derivative initially obtained was achieved by irradiation in the ultraviolet region, where this prepolymer shows maximum sensitivity. Immobilization of tyrosinase on this support involves a process of physical adsorption and intense hydrophobic interactions between the cinnamoyl groups of the support and related groups of the enzyme. The pH value, enzyme concentration and immobilization time were all important parameters affecting immobilization efficiency; also, enzyme immobilization efficiency correlated well with the tyrosinase isoelectric point. The immobilized enzyme showed an optimum measuring pH of 3.5 and greater activity at acid and neutral pH values than the soluble enzyme. The optimal reaction temperature was 35 °C and the temperature profile was broader than that of the free enzyme or of the enzyme immobilized on other supports. The apparent Michaelis constant of mushroom tyrosinase immobilized on the SOTCN derivative acting on 4‐tert‐butylcatechol (TBC) was 0.40 ± 0.02 mmol dm−3, which was lower than for the soluble enzyme, suggesting that the affinity of this enzyme for this substrate was greater when immobilized than when in solution. Immobilization stabilized the enzyme and made it less susceptible to activity loss during storage at pH values in the range 4–5.5, and the suicide inactivation of the immobilized tyrosinase was null or negligible in a reaction medium with 4‐tert‐butylcatechol at a concentration of 0.4 mmol dm−3. The results show that cinnamic carbohydrate esters of D‐sorbitol are an appropriate support for tyrosinase immobilization and could be of use for several tyrosinase applications. Copyright © 2005 Society of Chemical Industry
Characterization of synthetic nucleic acids by electrospray ionization quadrupole time‐of‐flight mass spectrometry
Authors: Oberacher Herbert , Niederstätter Harald , Parson Walther
Published: May 2005

The potential of electrospray ionization quadrupole‐quadrupole‐time‐of‐flight mass spectrometry (ESI‐QqTOF‐MS) for the characterization of synthetic nucleic acids was evaluated. Oligonucleotides ranging in size from 12 up to 51 nucleotides were analyzed via direct infusion MS as well as via liquid chromatography (LC) online hyphenated to MS. These experiments proved the outstanding mass spectrometric performance of the TOF mass analyzer in regard of accuracy, reproducibility, resolution, and sensitivity. During a 1‐min run, the monoisotopic mass of (dT)24was measured with a maximum relative mass deviation of 7.64 ppm proving the high mass accuracy of the TOF analyzer. Over a period of 1 h, mean deviations were determined in the range between −3.58 ppm and 3.06 ppm demonstrating the high stability of the applied external calibration. The molecular mass of a 51‐mer was measured with a deviation smaller than 3.23 ppm from the theoretical value. The resolution exceeded a value of m/Δm = 20 000 (m is the measured mass and Δm the full peak width at half‐maximum), which enabled the separation of the isotopic peaks of all investigated oligonucleotides. Because of the outstanding transmission and detection efficiency of the TOF mass analyzer, detection limits in the amol/µl to low fmol/µl range were reached. The usability of LC‐ESI‐QqTOF‐MS for the qualitative and quantitative analysis of synthetic oligonucleotide mixtures was demonstrated. Copyright © 2005 John Wiley & Sons, Ltd.
Diffusion tensor imaging of the developing human cerebrum
Authors: Gupta Rakesh K. , Hasan Khader M. , Trivedi Richa , Pradhan Mandakini , Das Vinita , Parikh Nehal A. , Narayana Ponnada A.
Published: June 2005

Diffusion tensor imaging (DTI) was performed on 15 fresh spontaneously or therapeutically aborted normal fetuses and five term infants at different gestational ages. Regional cortical fractional anisotropy (FA) values were observed to increase with gestational age (GA) from 15 to 28 weeks, followed by a decrease through 36 weeks. The early increase in the cortical FA value, which has never been reported before, is consistent with neuronal migration from the germinal matrix. A statistically significant inverse correlation between GA and the FA values in the germinal matrix was observed (r = –0.81, P = 0.004). In addition, there was a significant difference in the FA values in the right and left frontal cortices (P = 0.007, sign test), suggesting cortical lateralization during the early stage of development. Our studies suggest that the DTI‐estimated anisotropy could be useful in following neuronal migration, cortical maturation, and associated changes in the germinal matrix during early brain development. © 2005 Wiley‐Liss, Inc.
Gliotoxicity in hippocampal cultures is induced by transportable, but not by nontransportable, glutamate uptake inhibitors
Authors: Guiramand Janique , Martin Alexandra , de Jesus Ferreira Marie‐Celeste , Cohen‐Solal Catherine , Vignes Michel , Récasens Max
Published: June 2005

Extracellular glutamate is kept below a toxic level by glial and neuronal glutamate transporters. Here we show that the transportable glutamate uptake inhibitor L‐trans‐pyrrolidine‐2,4‐dicarboxylate (t‐PDC) induced cell death in mature, but not in immature, hippocampal neuron‐enriched cultures. The cell death produced by a 24‐hr treatment with t‐PDC was dose‐dependent and reached 85% of the cell population at a 250 μM concentration at 23 days in vitro (DIV). Immunocytochemistry experiments showed that, under these experimental conditions, t‐PDC killed not only neurons as expected but also glial cells. The N‐methyl‐D‐aspartate (NMDA) antagonist D‐2‐aminophosphonovalerate (D‐APV; 250 μM) only partially reversed this toxicity, completely protecting the neuronal cell population but not the glial population. The antioxidant compounds α‐tocopherol or Trolox, used at concentrations that reverse the oxidative stress‐induced toxicity, did not block the gliotoxicity specifically produced by t‐PDC in the presence of D‐APV. The nontransportable glutamate uptake inhibitor DL‐threo‐β‐benzyloxyaspartate (TBOA) elicited cell death only in mature, but not in immature, hippocampal cultures. The TBOA toxic effect was dose dependent and reached a plateau at 100 μM in 23‐DIV cultures. About 50% of the cell population died. TBOA affected essentially the neuronal population. D‐APV (250 μM) completely reversed this toxicity. It is concluded that nontransportable glutamate uptake inhibitors are neurotoxic via overactivation of NMDA receptors, whereas transportable glutamate uptake inhibitors induce both an NMDA‐dependent neurotoxicity and an NMDA‐ and oxidative stress‐independent gliotoxicity, but only in mature hippocampal cultures. © 2005 Wiley‐Liss, Inc.
N‐methyl‐D‐aspartate receptor and apoptosis in Alzheimer's disease and multiinfarct dementia
Authors: Fang Marong , Li Jicheng , Tiu S.C. , Zhang Lihong , Wang Mingwei , Yew David T.
Published: June 2005

This study investigates the role of excitotoxicity in Alzheimer's disease and in multiinfarct dementia by examining, via immunohistochemical methods, the number of cells that are positive for N‐methyl‐D‐aspartate (NMDA) receptor and the degree of colocalization between NMDA receptor and apoptosis markers such as TUNEL or activated caspase‐3 in the frontal cortex of individuals with these two conditions, comparing the results with those from subjects who died of normal aging. We showed an increased number of NMDA receptor‐positive cells and an increased number of TUNEL‐labeled cells in the frontal cortex of subjects with Alzheimer's disease, especially in the deeper layers of the cortex. However, only about 10% of cells showed colocalization of NMDA receptor with the apoptosis markers studied, suggesting that NMDA‐mediated excitotoxicity does not play a major role in neuronal apoptosis in Alzheimer's disease or in multiinfarct dementia. © 2005 Wiley‐Liss, Inc.
Time accurate fast wavelet‐Taylor Galerkin method for partial differential equations
Authors: Rathish Kumar B. V. , Mehra Mani
Published: June 2005

We introduce the concept of fast wavelet‐Taylor Galerkin methods for the numerical solution of partial differential equations. In wavelet‐Taylor Galerkin method discretization in time is performed before the wavelet based spatial approximation by introducing accurate generalizations of the standard Euler, θ and leap‐frog time‐stepping scheme with the help of Taylor series expansions in the time step. We will present two different time‐accurate wavelet schemes to solve the PDEs. First, numerical schemes taking advantage of the wavelet bases capabilities to compress the operators and sparse representation of functions which are smooth, except for in localized regions, up to any given accuracy are presented. Here numerical experiments deal with advection equation with the spiky solution in one dimension, two dimensions, and nonlinear equation with a shock in solution in two dimensions. Second, our schemes deal with more regular class of problems where wavelets are not efficient procedure for data compression but we can use the good approximation properties of wavelet. Here time‐accurate schemes lead to consistent mass matrix in an explicit time stepping, which can be solved by approximate factorization techniques. Numerical experiment deals with more regular class of problems like heat equation as well as coupled linear system in two dimensions. © 2005 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2006
Minimum time‐step criteria for the Galerkin finite element methods applied to one‐dimensional parabolic partial differential equations
Authors: Yang Chaodong , Gu Yongan
Published: June 2005

The finite element method has been well established for numerically solving parabolic partial differential equations (PDEs). Also it is well known that a too large time step should not be chosen in order to obtain a stable and accurate numerical solution. In this article, accuracy analysis shows that a too small time step should not be chosen either for some time‐stepping schemes. Otherwise, the accuracy of the numerical solution cannot be improved or can even be worsened in some cases. Furthermore, the so‐called minimum time step criteria are established for the Crank‐Nicolson scheme, the Galerkin‐time scheme, and the backward‐difference scheme used in the temporal discretization. For the forward‐difference scheme, no minimum time step exists as far as the accuracy is concerned. In the accuracy analysis, no specific initial and boundary conditions are invoked so that such established criteria can be applied to the parabolic PDEs subject to any initial and boundary conditions. These minimum time step criteria are verified in a series of numerical experiments for a one‐dimensional transient field problem with a known analytical solution. The minimum time step criteria developed in this study are useful for choosing appropriate time steps in numerical simulations of practical engineering problems. © 2005 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2006
Pseudomonas aeruginosa infection: An uncommon cause of post‐renal obstruction following induction therapy for acute lymphoblastic leukemia
Authors: Burghardt Karolina M. , Leonard Michael , Feber Janusz , Halton Jacqueline , Filler Guido
Published: June 2005

A 14‐month‐old infant presented with gastroenteritis with febrile pancytopenia and was diagnosed with acute lymphocytic leukemia (ALL). Ten days post induction therapy, the patient developed hypertension that was ascribed to steroid therapy and treated with metoprolol and amlodipine. As leukocyte numbers began to recover the asymptomatic patient became anuric. Ultrasound showed echoic floating structures in the bladder. Following cystoscopy and retrograde pyelography examination, purulent debris was irrigated from the bladder and grew Pseudomonas aeruginosa. Ciprofloxacin therapy was initiated and renal function was restored within 2 days. The case highlights the potential for renal obstruction after neutropenia recovery in children undergoing induction therapy for ALL. Pediatr Blood Cancer 2006, 46:512–513. © 2005 Wiley‐Liss, Inc.
Histologic survey of neuroblastomas after intensive induction chemotherapy
Authors: Tsuchida Yoshiaki , Miyauchi Jun , Kuroiwa Minoru , Suzuki Norio , Sakamoto Jun , Suzuki Makoto , Shitara Toshiji
Published: June 2005

Background

Histology after intensive induction chemotherapy is expected to become a beacon indicating when and how extensively radical surgery and lymph node dissection should be performed in advanced neuroblastoma. A thorough histologic review of surgical specimens was undertaken.

Procedure

All specimens from 34 patients who were pretreated intensively (≥3 cycles) with recent chemotherapy were reviewed. Thirty patients were >12 months of age with stage 3/4 disease, and 4 were <12 months of age but with MYCN‐amplified stage 4 diseases. After 3 to 7 cycles (mean, 4.3 cycles) of induction chemotherapy, patients underwent radical surgery of the primary tumor and lymph nodes in all retroperitoneal sections. A single pathologist reviewed all of the specimens, and histologic chemotherapeutic effects were graded as: (+++), <1% viable tumor; (++), 1%–10% viable tumor; (+), 11%–50% viable tumor; (±), 51%–90% viable tumor; and (−), >91% viable tumor.

Results

Grade (+++) effects were observed in 56% of patients treated with the new regimens, whereas grade (+++) was seen in only 20% treated with regimens before 1991. Operation time and blood loss were 7 hr and 6 min (P = 0.087) and 646 ml (P = 0.064), respectively, in patients with >5 cycles (mean, 5.3 cycles) of chemotherapy, while they were 7 hr and 50 min and 1,168 ml, respectively, in those with approximately 3 cycles (mean, 3.2 cycles). Histologically, metastases were found in the contralateral nodes beyond the aorta in 92% of those whose tumor originated on the left, and in 80% of those with tumors occurring on the right.

Conclusions

Five cycles of induction chemotherapy did not improve histologic chemotherapeutic effects, but helped to facilitate a shorter operation time and less blood loss than 3 cycles of chemotherapy. Surgery after 5 cycles of 98A3 also appears to be easier to perform than that after 3 cycles of A1/new A1. Only 14% of the children treated before 1985 with the St. Jude protocols experienced grade (+++) chemotherapeutic effects, and 22% of the patients treated before 1991 with regimen A1, or new A1 of the Study Group of Japan showed grade (+++) effects, whereas 56% of the patients treated after 1991 with either regimen A3 or 98A3 exhibited grade (+++) chemotherapeutic effects. Histologic chemotherapeutic effects were roughly parallel with a good prognosis. Pediatr Blood Cancer © 2005 Wiley‐Liss, Inc.
Chronic granulomatous disease presenting with disseminated intracranial aspergillosis
Authors: Alsultan Abdul , Williams Marc S. , Lubner Sam , Goldman Frederick D.
Published: June 2005

We describe an 8‐year‐old boy who presented with multiple unresectable aspergillus brain abscesses as the initial presentation of X‐linked chronic granulomatous disease (CGD). He failed initial therapy with amphotericin B, but was subsequently salvaged with voriconazole. CGD should be considered in the differential diagnosis for all children presenting with invasive fungal infections, particularly, those involving the central nervous system (CNS). Whereas, optimal pharmacologic therapy is still unknown for CNS aspergillosis, voriconazole may have an advantage due to its ability to cross the blood brain barrier and excellent oral absorption and bioavailability. © 2005 Wiley‐Liss, Inc.
Synthesis and characterization of poly(fluorene)‐based copolymers containing various 1,3,4‐oxadiazole pendants
Authors: Sung Hsiao‐Hsien , Lin Hong‐Cheu
Published: May 2005

A series of soluble alternating poly(fluorene)‐based copolymers containing electron‐transporting 1,3,4‐oxadiazole (OXD) and hole‐transporting carbazole pendants attached to the C‐9 position of fluorene units by long alkyl spacers were synthesized. These copolymers possess mesogenic and nonmesogenic pendants attached to a rigid mesogenic poly(fluorene) (PF) backbone. All these polymers exhibit glass‐forming liquid crystalline properties, including the nematic and smectic A (SmA) phases, and reveal much wider mesophasic temperature ranges than that of PF. The thermal properties and mesomorphism of these conjugated polymers are mainly affected by the nature of these pendants, and thus the mesophasic temperature ranges and glass‐forming properties are greatly enhanced by introducing the OXD pendants. In addition, the tendencies of crystallization and aggregation of PF are also suppressed by introducing the OXD pendants. A single layer device with P4 as an emitter shows a turn‐on voltage of 5 V and a bright luminescence of 2694 cd/m2 at 11 V with a power efficiency of 1.28 cd/A at 100 mA/cm2. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2700–2711, 2005
From thermoplastic elastomers to designed biomaterials
Authors: Kennedy Joseph P.
Published: June 2005

This highlight is about my metamorphosis from a cationic polymerization chemist to a biomaterialist (no pun intended) and some of the main events on the road. My earlier career faded away with the discovery of living cationic polymerizations, chronicled in my 1999 highlight, but it also put me on the road to designed biomaterials. My new career started with, and still focuses on, the creation of new polymeric architectures, mainly by cationic techniques, for toughened bone cements, injectable intervertebral discs, nonclogging artificial blood vessels, and amphiphilic networks for controlled drug delivery and immunoisolatory membranes. The enormous complexities of immunoisolation of pancreatic islets are now center stage, and lately we have been using all kinds of techniques to make unique membranes to correct type 1 diabetes. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2951–2963, 2005
Dynamic NMR study of the electronic state of heteroaromatics. VIII. The influence of the exo‐ and endocyclic heteroatoms
Authors: Kleinpeter E. , Spitzner R. , Schroth W. , Philaja K.
Published: May 2005

The 1H/13C‐n.m.r. chemical shifts and rotational barriers for the exocyclic partial C,N‐double bonds of some pyran‐ (1–3) and thiopyranthiones 4 and 5 are discussed in relation to the π‐electron density in these strongly polar heteroaromatics.
Aromaticity as a Quantitative Concept. 2. Sixteen familiar five‐ and six‐membered monocyclic heterocycles
Authors: Katritzky Alan R. , Feygelman Vladimir , Musumarra Giuseppe , Barczynski Piotr , Szafran Miroslaw
Published: May 2005

Restudy of an almost complete data set of 12 characteristics for 16 common heterocycles confirms the previous conclusion [1] of the independence of „classical”︁ and of „magnetic”︁ aromaticity. The scores for the individual heterocycles correlate well with their chemical structure.
Aromaticity as a Quantitative Concept. 3. Benzo‐fused five‐ and six‐membered heterocycles
Authors: Katritzky Alan R. , Feygelman Vladimir , Musumarra Giuseppe , Barczynski Piotr , Szafran Miroslaw
Published: May 2005

A rather complete data set for 12 characteristics of 18 common benzo‐fused heterocycles yields two significant principal components. The loadings of the characteristics show a close correlation with those found for the same characteristics of monocyclic heterocycles. The scores for each bicycle are also closely related to those for the corresponding monocycle. The method demonstrates considerable predictive power.
Aza‐Enamine. IX. UV/VIS‐ und NMR‐spektroskopische Interpretation der Elektronenstruktur in Aldehydhydrazonen und daraus hergestellten Aza‐Trimethinen
Authors: Brehme Rainer , Radeglia Reiner , Gründemann Egon
Published: May 2005

Aza‐Enamines. IX. UV/VIS and N.M.R. Spectroscopic Interpretation of the Electron Structure in Aldehyde‐N,N‐dialkylhydrazones and in Aza‐trimethines Prepared from These

The n.m.r. and u.v./vis spectroscopic data of the compounds 2, 3 and 4 – synthesized by electrophilic substitution at the azomethine carbon atom of the aldehyde hydrazones 1 according to the aza‐enamine‐concept – are reported. Compared to the respective C‐atom of the starting hydrazones 1 the azomethine‐C‐atom of the compounds 2–4 exhibits a 13C‐n.m.r. shift not corresponding to usual substituent effects. Our interpretation for this and for the u.v./vis spectroscopic data, too, is a simultaneous existence of both an aza‐trimethine structural unit and an aromatic structure in the compounds 2–4.
Zur Molekülverknüpfung mit Schwefelchloriden. IX. Reaktion von Schwefeldichlorid mit N‐Allyl‐anilinen. Eine Synthese für 2‐Chlormethyl‐2,3‐dihydro‐1,4‐benzothiazine
Authors: Mühlstädt M. , Hollmann K. , Möder M.
Published: May 2005

Molecule Linkage by Sulfur Chlorides. IX. The Addition Reaction of Sulfur Dichlorides with N‐Allyl‐anilines. A Synthesis for 2‐Chloromethyl‐2,3‐dihydrobenzo‐1,4‐thiazines

Reactions of different substituted N‐allyl‐anilines 1 with sulfur dichloride yield 2‐chloromethyl‐2,3‐dihydrobenzo‐1,4‐thiazines 3a–i. The identification of the products was carried out by mass spectroscopy and 1H‐n.m.r.‐spectroscopy. The seven‐membered cyclic isomers of the S, N‐heterocycles 3, dihydro‐benzo‐1,5‐thiazepanes 5 were not obtained.
N.M.R. Studies on Aminated Dinitrobenzofuroxan and Dinitrobenzofurazan Derivatives
Authors: Gründemann E. , Niclas H.‐J. , Göhrmann B.
Published: May 2005

The 13C‐n.m.r. chemical shifts of σ‐NC‐bonded Meisenheimer complexes 3, 5 and their corresponding aminated dinitrobenzofurazans 4 and dinitrobenzofuroxans 6 were determined. The chemical shifts are discussed as a function of electronic substituent effects.

The assignment was performed by means of 1H13C coupling constants and by comparison with che 13C‐chemical shifts of appropriate model compounds. The 13C‐n.m.r. spectra of Meisenheimer tomplexes 3 reveal doubling of signals, indicating a hindered rotation at the NCHO bond.
Distribution of alkyl derivatives of 2‐hydroxybenzophenone oximes and aliphatic α‐hydroxyoximes in hydrocarbon‐water and their polarity parameters
Authors: Olszanowski Andrzej , Borowiak‐Resterna Aleksandra
Published: May 2005

The values of partition coefficient of 5‐alkyl‐2‐hydroxybenzophenone oxime derivatives and aliphatic α‐hydroxyketone oximes with various lengths of carbon chains were determined for toluene‐water and heptane‐water systems. The dimerization constants of alkyl 2‐hydroxybenzo‐phenone oxime derivatives in toluene and heptane, and the values of polarity parameters of aliphatic α‐hydroxyoximes were determined by gas chromatography. It was found that the partition coefficients of both groups of oximes decrease with decreasing length of the alkyl chain. The partition coefficients are higher for toluene‐water system than for heptane‐water system. A correlation exists between the partition coefficients and the polarity parameters of hydroxyoximes.
Synthese eines neuen Thienospirans: 6,7‐Dihydro‐1′‐methyl‐spiro[benzo[b]thiophen‐4(5H),2′‐piperidin]
Authors: Fröhlich Hannes , Gmeiner Günter , Sauter Fritz
Published: May 2005

Synthesis of a New Thienospiran: 6,7‐Dihylro‐1′‐methyl‐spiro[benzo[j]thioxhen‐4(5H),2′‐piperidine]

The title spiro compound 6 – a N‐methyl derivative of a new parent system ‐ has been synthesized from nitrile 8 via 4‐phenoxybutylation, followed by modified Schmidt degradation, ensuing O‐deprotection and final cyclization. The constitution of the target compound and of all intermediates is established by 1H‐n.m.r. and 13C‐n.m.r.‐spectroscopy and by microelementary analysis.
Organophosphorus chemistry. 16. The Reaction of Furfurylidenemalonitrile with Alkyl Phosphites
Authors: Abdou Wafaa M. , Khidre Maha D. , Mahran Mohamed R.
Published: May 2005

Dialkyl phosphites (2a–c) react with furfurylidenemalonitrile (1) to give the corresponding 1:1 phosphonate adducts 3a–c. On the other hand, trialkyl phosphites (6a, b) affected C‐alkylation of the exocyclic ethylenic linkage in compound (1) to give the respective phosphonate 7a, b.
The Tautomerism between Ketene Aminals and Amidines
Authors: Huang Zhi‐Tang , Gan Wei‐Xing , Li Li‐Pu
Published: May 2005

A tautomerie equilibrium between ketene aminals and amidines is disclosed as an electron‐donating group is substituted at the para‐position of the phenyl ring in 4.
Cyclocondensation of 4‐Benzyl‐1‐hydrazinophthalazine
Authors: El‐Feky Said , Bayoumy Bashner E.
Published: May 2005

1‐Hydrazino‐4‐benzylphthalazine 1 underwent closure and/or condensation reaction with formic acid, acetic acid, acetic anhydride, trifluoroacetic anhydride, ortho esteres, aldehydes, urea or carbon disulphide to afford the N‐formyl 3a, N‐acyl 3b, and the appropriate 3‐substituted‐6‐benzyl‐s‐triazolo [3,4‐a] phthalazines 4a, c, 7, 8. Alkylation of the obtained s‐triazolo[3,4‐a]‐phthalazine‐3‐thione 7 and s‐triazolo [3,4‐a] phthalazin‐3‐one 8 with N‐substituted chloroacetamides gave the thioether 9 and N‐substitution products 10, respectively. Likewise, applying Mannich conditions of the previously mentioned intermediates 7 and 8 yielded the N‐Mannich bases (11 and 12). The new products were characterized by their elemental and spectral data.
Reaction of Tetracyanoethylene with Arylazoaminopyrazoles via charge‐transfer complexation
Authors: Hassan Alaa A. , Ibrahim Yusria R. , Mohamed Nasr K. , Mourad Aboul‐Fetouh E.
Published: May 2005

Arylazoaminopyrazoles (1a–d) reacts with tetracyanoethylene (TCNE) to yield pyrazolo[1,5‐a]pyrimidines (9) via charge‐transfer (CT) complex formation. The effect of the substituents on the basicity of the pyrazole nucleus as well as the complexation centre in different types of pyrazoles is discussed.
Synthese von Cyclobutan durch Dehalogenierung von 1,4‐Dihalogenbutanen mit Alkalimetalldämpfen. Zur Relation von radikalischen und metallorganischen Reaktionskanälen
Authors: Volnina S. A. , Avakjan V. G. , Guselnikov L. E. , Al Yaya A.
Published: May 2005

Synthesis of Cyclobutane by Dehalogenation of 1,4‐Dihalogenbutane in Alkali‐Metall‐Bathway. The Relation of Radical and Metallorganic Reaction‐channels.

Gasphase dehalogenation of 1,4‐dichloro‐, 1‐chlor‐4‐bromo, 1,4‐dibrombutanes and 1,4‐dibrompentane by Na/K vapors produces cyclobutane resp. methylcyclobutane with selectivities of resp. 55.5, 46.7, 32.0 and 17 moles/100 moles. Side products of the reaction are ethylene and hydrogen, yields of which increase with increasing temperature and rising degree of substitution of chlorine by bromine. A mechanism is discussed in which the initiation step is the generation of halobutyl radicals of the type H2Ċ(CH2)2CH2X (X = Cl, Br) which are reacting further in two ways – by formation of tetramethylenediradical, splitting off the second halogen atom, or by the formation of the metallorganic compound 1‐kalium‐4‐halogenbutane, which further cyclisize to cyclobutane splitting off KX.

Using some methods of theoretical chemistry such as quantumchemical calculations based on ab initio (STO‐3G) and semiempirical (AM1) structures, on the relative energies of conformeres of halogenbutylradicals and on models of the metallorganic intermediates, but also by conformation calculations of the content of rotation isomers of the intermediate formed, the correlation between the two reaction channels in dependence of the type of halogen was estimated. The calculations showed, that only about 20% of cyclobutane are generated by the radical pathway. The high predominance of the metallorganic channel in the case of 1,4‐dichlorbutaneis caused by the high lifetime of chlorobutyl radicals in comparison with his bromoanalogues.