bluuebunny/crossref_metadata_2025_split huggingface dataset:
Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis
Authors: Heath Paul R. , Shaw Pamela J. 
Published: October 2002

AbstractExcitotoxicity may play a role in certain disorders of the motor system thought to be caused by environmentally acquired toxins, including lathyrism and domoic acid poisoning. Motor neurons appear to be particularly susceptible to toxicity mediated via α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA)–kainate receptors. There is a body of evidence implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). Interference with glutamate‐mediated toxicity is so far the only neuroprotective therapeutic strategy that has shown benefit in terms of slowing disease progression in ALS patients. Biochemical studies have shown decreased glutamate levels in central nervous system (CNS) tissue and increased levels in the cerebrospinal fluid (CSF) of ALS patients. CSF from ALS patients is toxic to neurons in culture, apparently via a mechanism involving AMPA receptor activation. There is evidence for altered expression and function of glial glutamate transporters in ALS, particularly excitatory amino acid transporter 2 (EAAT2). Abnormal splice variants of EAAT2 have been detected in human CNS. Mitochondrial dysfunction may contribute to excitotoxicity in ALS. Induction of neuronal nitric oxide synthase and cyclooxygenase 2 in ALS may also lead to significant interactions with regulation of the glutamate transmitter system. Certain features of motor neurons may predispose them to the neurodegenerative process in ALS, such as the cell size, mitochondrial activity, neurofilament content, and relative lack of certain calcium‐binding proteins and molecular chaperones. Motor neurons appear vulnerable to toxicity mediated by calcium‐permeable AMPA receptors. The relatively low expression of the glutamate receptor 2 (GluR2) AMPA receptor subunit and the high current density caused by the large number and density of cell surface AMPA receptors are potentially important factors that may predispose to such toxicity. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 438–458, 2002
Biopsy sampling requirements for the estimation of muscle capillarization
Authors: Porter Michelle M. , Koolage Chris W. , Lexell Jan 
Published: October 2002

AbstractThe aim of this study was to determine the number of tibialis anterior biopsy samples and muscle fibers required to estimate the capillary supply of individual muscle fibers (C:Fi). C:Fi was calculated for 25 type 1 fibers in each of 8 images from 3 biopsies of 5 young healthy individuals. Sequential estimation analysis indicated that 50 fibers from one biopsy are sufficient to characterize the C:Fi of the tibialis anterior for a group of subjects. Thus, when analyzing the capillarization of the tibialis anterior, the requirements of only one biopsy sample and 50 fibers means a great reduction in time for analysis and in the invasiveness of the procedure. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 546–548, 2002
Electrocardiographic findings in mdx mice: A cardiac phenotype of Duchenne muscular dystrophy
Authors: Chu Victor , Otero Jose M. , Lopez Orlando , Sullivan Matthew F. , Morgan James P. , Amende Ivo , Hampton Thomas G. 
Published: October 2002

AbstractThe mdx mouse is a model of Duchenne muscular dystrophy (DMD). As many DMD patients die of cardiac failure, we investigated whether mdx mice exhibited clinically relevant cardiac phenotypes. We applied a recently developed method for noninvasively recording electrocardiograms (ECGs) to study male mdx mice (n = 15) and control mice (n = 15). The mdx mice had significant tachycardia and decreased heart rate variability, consistent with observations in DMD patients. Heart rate was nearly 15% faster in mdx mice than control mice (P < 0.05). The rate‐corrected QT interval duration and PR interval were shorter in mdx compared to control mice (P < 0.05). The muscarinic antagonist atropine significantly increased heart rate and decreased PR interval in C57 mice. In contrast, atropine significantly decreased heart rate and increased PR interval in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. Baseline ECGs and contrary responses to muscarinic blockade by atropine in mice deficient in neuronal nitric oxide synthase (nNOS) suggest that the autonomic dysfunction in mdx mice may be independent of decreased myocardial nNOS. These electrocardiographic findings in dystrophin‐deficient mice may provide new bases for diagnosing, understanding, and treating DMD patients. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 513–519, 2002
Randomized, controlled trial of intravenous immunoglobulin in myasthenia gravis
Authors: Wolfe Gil I. , Barohn Richard J. , Foster Barbara M. , Jackson Carlayne E. , Kissel John T. , Day John W. , Thornton Charles A. , Nations Sharon P. , Bryan Wilson W. , Amato Anthony A. , Freimer Miriam L. , Parry Gareth J. 
Published: October 2002

AbstractWe initiated a randomized, double‐blinded, placebo‐controlled trial of intravenous immunoglobulin (IVIG) treatment in myasthenia gravis (MG). Patients received IVIG 2 gm/kg at induction and 1 gm/kg after 3 weeks vs. 5% albumin placebo. The primary efficacy measurement was the change in the quantitative MG Score (QMG) at day 42. Fifteen patients were enrolled (6 to IVIG; 9 to placebo) before the study was terminated because of insufficient IVIG inventories. At day 42, there was no significant difference in primary or secondary outcome measurements between the two groups. In a subsequent 6‐week open‐label study of IVIG, positive trends were observed. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 549–552, 2002
Axonal neuropathy in chronic peripheral arterial occlusive disease
Authors: Weber Frank , Ziegler Andrea 
Published: October 2002

AbstractChronic peripheral arterial occlusive disease of the lower limbs may cause tissue damage. Type and extent of peripheral nerve involvement is controversial. We examined 25 patients with peripheral arterial occlusive disease in various grades of severity and 37 age‐matched healthy controls using conventional angiography and motor and sensory nerve conduction tests. Subjects with confounding factors for peripheral neuropathies were excluded. We found prolongation of distal motor latencies, decrease of motor and sensory nerve conduction velocities, and reduction in amplitude of the compound muscle action potential. Amplitudes of the compound muscle action potentials were lower in patients with pain at rest than in patients with intermittent claudication and decreased with increasing neurological disability score. Sural nerve conduction velocity, peroneal nerve F‐wave chronodispersion, and tibial nerve F‐wave persistence were the most frequent abnormal findings. Therefore we concluded that chronic peripheral arterial occlusive disease causes axonal degeneration, resulting in axonal polyneuropathy. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 471–476, 2002
Altered regional brain glucose metabolism in Duchenne muscular dystrophy: A pet study
Authors: Lee Joon Soo , Pfund Zoltán , Juhász Csaba , Behen Michael E. , Muzik Otto , Chugani Diane C. , Nigro Michael A. , Chugani Harry T. 
Published: October 2002

AbstractThe basis for cognitive impairment in Duchenne muscular dystrophy (DMD) is not well understood but may be related to abnormal expression of dystrophin in brain. The aim of this study was to determine whether regional brain glucose metabolism is altered in children with DMD and whether such metabolic disturbances are localized to regions shown to be normally rich in dystrophin expression. Ten boys (mean age, 11.8 years) with DMD and 17 normal adults as a control group (mean age, 27.6 years) underwent 2‐deoxy‐2[18F]fluoro‐D‐glucose positron emission tomography (PET) and neuropsychological evaluation. The PET data were analyzed by statistical parametric mapping (SPM). The SPM analysis showed five clusters of decreased glucose metabolism in children with DMD, including the

medial temporal structures and cerebellum bilaterally and the sensorimotor and lateral temporal cortex on the right side. At the voxel level, significant glucose hypometabolism was found in the right postcentral and middle temporal gyri, uncus, and VIIIB cerebellar lobule, as well as in the left hippocampal gyrus and cerebellar lobule. The neuropsychological profile of the DMD group revealed borderline nonverbal intellectual functioning, impaired manual dexterity bilaterally, borderline cognitive functioning, and internalizing behavioral difficulties. Our findings demonstrate region‐specific hypometabolism, as well as cognitive and behavioral deficits in DMD children. As the regions showing hypometabolism on PET include those normally rich in dystrophin expression, it will be important to determine whether the hypometabolic regions also show cytoarchitectural abnormalities related to the lack of dystrophin. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26:506‐512, 2002
Timing of neurodegeneration and beta‐amyloid (Aβ) peptide deposition in the brain of aging kokanee salmon
Authors: Maldonado Tammy A. , Jones Richard E. , Norris David O. 
Published: October 2002

AbstractBrains of kokanee salmon (Oncorhynchus nerka kennerlyi) in one of four reproductive stages (sexually immature, maturing, sexually mature, and spawning) were stained with cresyl violet and silver stain to visualize neurodegeneration. These reproductive stages correlate with increasing somatic aging of kokanee salmon, which die after spawning. Twenty‐four regions of each brain were examined. Brains of sexually immature fish exhibited low levels of neurodegeneration, whereas neurodegeneration was more marked in maturing fish and greatest in spawning fish. Neurodegeneration was present in specific regions of the telencephalon, diencephalon, mesencephalon, and rhombencephalon. Pyknotic neurons were observed in all regions previously reported to be immunopositive for Aβ. Regions that did not exhibit neurodegeneration during aging included the magnocellular vestibular nucleus, the nucleus lateralis tuberis of the hypothalamus, and Purkinje cells of the cerebellum, all of which also lack Aβ; perhaps these regions are neuroprotected. In 14 of 16 brain areas for which data were available on both the increase in Aβ deposition and pyknosis, neurodegeneration preceded or appeared more or less simultaneously with Aβ production, whereas in only two regions did Aβ deposition precede neurodegeneration. This information supports the hypothesis that Aβ deposition is a downstream product of neurodegeneration in most brain regions. Other conclusions are that the degree of neurodegeneration varies among brain regions, neurodegeneration begins in maturing fish and peaks in spawning fish, the timing of neurodegeneration varies among brain regions, and some regions do not exhibit accelerated neurodegeneration during aging. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 21–35, 2002
Aging fetal and juvenile skeletons from Roman Period Egypt using basiocciput osteometrics
Authors: Tocheri Matthew W. , Molto J. Eldon 
Published: October 2002

AbstractThis paper tests the use of basiocciput osteometrics against those of femoral diaphyseal length and dental development for aging fetal and juvenile skeletal remains. The study sample consists of 39 fetal and juvenile skeletons recovered from Kellis 2, a Roman Period cemetery in Dakhleh, Egypt. The results add to the corpus of data supporting the reliability of this method for use in both bioarchaeological and forensic contexts. Copyright © 2002 John Wiley & Sons, Ltd.
For richer or for poorer: Marriage as an antipoverty strategy
Authors: Thomas Adam , Sawhill Isabel 
Published: October 2002

AbstractThis study examines the effects of changes in family structure on children's economic well‐being.
An initial shift‐share analysis indicates that, had the proportion of children living in
female‐headed families remained constant since 1970, the 1998 child poverty rate would have been 4.4
percentage points lower than its actual 1998 level of 18.3 percent. The March 1999 Current Population Survey is
then used to conduct a second analysis in which marriages are simulated between single mothers and demographically
similar, unrelated males. The microsimulation analysis addresses some of the shortcomings of the
shift‐share approach by making it possible to account for the possibility of a shortage of marriageable
men, to control for unobservable differences between married men and women and their unmarried counterparts, and
to measure directly the effects of increases in marriage on the economic well‐being of children. Results
from the microsimulation analysis suggest that, had the proportion of children living in female‐headed
families remained constant since 1970, the child poverty rate would have been 3.4 percentage points lower than its
actual 1998 level. Among children whose mother participated in a simulated marriage, the poverty rate would have
fallen by almost two‐thirds. © 2002 by the Association for Public Policy Analysis and Management.
Stakeholder partnerships as collaborative policymaking: Evaluation criteria applied to watershed management in California and Washington
Authors: Leach William D. , Pelkey Neil W. , Sabatier Paul A. 
Published: October 2002

AbstractPublic policymaking and implementation in the United States are increasingly handled through local,
consensus‐seeking partnerships involving most affected stakeholders. This paper formalizes the concept
of a stakeholder partnership, and proposes techniques for using interviews, surveys, and documents to measure
each of six evaluation criteria. Then the criteria are applied to 44 watershed partnerships in California and
Washington. The data suggest that each criterion makes a unique contribution to the overall evaluation, and
together the criteria reflect a range of partnership goals—both short‐term and long‐term,
substantive and instrumental. Success takes time—frequently about 48 months to achieve major milestones,
such as formal agreements and implementation of restoration, education, or monitoring projects. Stakeholders
perceive that their partnerships have been most effective at addressing local problems and at addressing
serious problems—not just uncontroversial issues, as previously hypothesized. On the other hand, they
perceive that partnerships have occasionally aggravated problems involving the economy, regulation, and threats
to property rights. © 2002 by the Association for Public Policy Analysis and Management.
Postmarketing drug dosage changes of 499 FDA‐approved new molecular entities, 1980–1999
Authors: Cross James , Lee Howard , Westelinck Agnes , Nelson Julie , Grudzinskas Charles , Peck Carl 
Published: October 2002

AbstractPurposeRisks and benefits of marketed drugs can be improved by changing their labels to optimize dosage regimens for indicated populations. Such postmarketing label changes may reflect the quality of pre‐marketing development, regulatory review, and postmarketing surveillance. We documented dosage changes of FDA‐approved new molecular entities (NMEs), and investigated trends over time and across therapeutic groups, on the premise that improved drug development methods have yielded fewer postmarketing label changes over time.MethodsWe compiled a list of NMEs approved by FDA from 1 January 1980 to 31 December 1999 using FDA's website, Freedom of Information Act request, and PhRMA (Pharmaceutical Research and Manufacturers of America) database. Original labeled dosages and indicated patient populations were tracked in labels in thePhysician's Desk Reference®. Time and covariate‐adjusted risks for dosage changes by 5‐year epoch and therapeutic groups were estimated by survival analysis.ResultsOf 499 NMEs, 354 (71%) were evaluable. Dosage changes in indicated populations occurred in 73 NMEs (21%). A total of 58 (79%) were safety‐motivated, net dosage decreases. Percentage of NMEs with changes by therapeutic group ranged from 27.3% for neuropharmacologic drugs to 13.6% for miscellaneous drugs. Median time to change following approval fell from 6.5 years (1980–1984) to 2.0 years (1995–1999). Contrary to our premise, 1995–1999 NMEs were 3.15 times more likely to change in comparison to 1980–1984 NMEs (p = 0.008, Cox analysis).ConclusionsDosages of one in five NMEs changed, four in five changes were safety reductions. Increasing frequency of changes, independent of therapeutic group, may reflect intensified postmarketing surveillance and underscores the need to improve pre‐marketing optimization of dosage and indicated population. Copyright © 2002 John Wiley & Sons, Ltd.
Solvent effects in the Grignard reaction with alkynes
Authors: Tuulmets A. , Pällin V. , Tammiku‐Taul J. , Burk P. , Raie K. 
Published: October 2002

AbstractKinetic studies were carried out on the reaction of phenylmagnesium bromide with hex‐1‐yne in diethyl ether, and in binary mixtures of diethyl ether with toluene, chlorobenzene and dichloromethane. The reaction was accelerated by addition of non‐donating solvents. The replacement of a coordinated solvent molecule by the alkyne is necessary for the reaction to proceed, according to density functional theory (DFT) calculations with B3LYP/6–31 + G* method. The non‐donating solvents accelerate the reaction by shifting the replacement equilibrium in favour of the complex formation. An analysis in terms of the Koppel–Palm equation revealed a rate decrease with increase in solvent polarity and polarizability. Copyright © 2002 John Wiley & Sons, Ltd.
Correlation analysis of reactivity in oxidation of substituted benzyl alcohols by tetrabutylammonium tribromide
Authors: Kumar Ashok , Sharma Pradeep K. , Banerji Kalyan K. 
Published: October 2002

AbstractOxidation of benzyl alcohol and some ortho‐, meta‐ and para‐monosubstituted benzyl alcohols by tetrabutylammonium tribromide (TBATB) in aqueous acetic acid leads to the formation of corresponding benzaldehydes. The reaction is first order each in TBATB and the alcohol. The oxidation of [1,1‐2H2]benzyl alcohol (PhCD2OH) exhibited a substantial kinetic isotope effect. Addition of tetrabutylammonium chloride or potassium bromide did not affect the rate. Tribromide ion has been postulated as the reactive oxidizing species. The reaction rate increases with increase in the polarity of the solvent. The rates of oxidation of meta‐ and para‐substituted benzyl alcohols showed excellent correlation in terms of Charton's triparametric LDR, equation whereas the oxidation of ortho‐substituted benzyl alcohols correlated best with the LDRS equation. The oxidation of para‐substituted benzyl alcohols is more susceptible to the delocalization effect than is the oxidation of ortho‐ and meta‐substituted compounds, which display a greater dependence on the field effect. The positive value of η suggests the presence of an electron‐deficient reaction centre in the rate‐determining step. The reaction is subject to steric acceleration by the ortho‐substituents. A suitable mechanism is proposed. Copyright © 2002 John Wiley & Sons, Ltd.
Reversible addition–fragmentation chain‐transfer polymerization: Unambiguous end‐group assignment via electrospray ionization mass spectrometry
Authors: Vana Philipp , Albertin Luca , Barner Leonie , Davis Thomas P. , Barner‐Kowollik Christopher 
Published: October 2002

AbstractElectrospray ionization mass spectrometry was performed to identify the structure of polymeric methyl acrylates generated via the cumyl dithiobenzoate (CDB), cumyl p‐fluorodithiobenzoate (CPFDB), and 1‐phenylethyl dithiobenzoate (PEDB) mediated reversible addition–fragmentation chain‐transfer (RAFT) polymerizations. The relatively simple spectra clearly demonstrate the end groups of this living free‐radical polymerization technique. Only polymeric chains carrying one leaving group of the RAFT agent and the dithiobenzoate end group as the active RAFT center were discovered. Multiple‐stage mass spectrometric experiments and oxidation of the dithioester end group confirmed the structure of the generated polymers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 4032–4037, 2002
Long‐term rates of mass wasting in Mesters Vig, northeast Greenland: notes on a re‐survey
Authors: Carver Steve , Mikkelsen Naja , Woodward John 
Published: October 2002

AbstractRe‐surveys of surviving mass‐wasting target lines established by A.L. Washburn in the late 1950s in the Mesters Vig area, northeast Greenland, are used to derive estimates of long‐term mass wasting in the area. Rates of 2.9–8.1 cm.yr−1 are calculated for a 2.5–3° slope and 1.5–30.4 cm.yr−1 for a gelifluction lobe on a 15–23° slope. Compared to Washburn's short‐term measurements for the same sites these long‐term rates suggest a general increase in the rate of mass wasting in the Mesters Vig area over the last 40 years. This increase may be related to a general pattern of climatic amelioration for the east coast of Greenland. Copyright © 2002 John Wiley & Sons, Ltd.
Active‐layer mapping at regional scales: a 13‐year spatial time series for the Kuparuk region, north‐central Alaska
Authors: Shiklomanov N. I. , Nelson F. E. 
Published: October 2002

AbstractResults from extensive, spatially‐oriented field investigations conducted in the Kuparuk River region of north‐central Alaska were used in conjunction with a simple analytical procedure to provide a comprehensive analysis of active‐layer variability under contemporary climate. This approach, based on Stefan's solution to the heat‐conduction problem with phase change, uses air temperature as the forcing function. An edaphic parameter represents the landcover‐specific response of the ground thermal regime to such local factors as lateral variations in soil, vegetation and moisture conditions. Regional estimates of climatic conditions were used within the framework of the spatial active‐layer model to map active‐layer thickness over the Kuparuk region on an annual basis, yielding a 13‐year spatial time series of regional thaw‐depth estimates. Results indicate that high‐resolution active‐layer mapping at regional scales is feasible given moderate amounts of climatic and edaphic information, obtained through extensive active‐layer sampling at locations representative of a number of environmental conditions. The analysis of annual thaw‐depth fields indicates that interannual climatic variability causes significant changes in active‐layer thickness. Copyright © 2002 John Wiley & Sons, Ltd.