bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke
Authors: Chen Jieli , Zhang Zheng Gang , Li Yi , Wang Ying , Wang Lei , Jiang Hao , Zhang Chenling , Lu Mei , Katakowski Mark , Feldkamp Carolyn S. , Chopp Michael 
Published: May 2003

AbstractWe demonstrate that the 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors atorvastatin and simvastatin enhance functional outcome and induce brain plasticity when administered after stroke to rats. With atorvastatin treatment initiated 1 day after stroke, animals exhibited significant increases in vascular endothelial growth factor, cyclic guanosine monophosphate, angiogenesis, endogenous cell proliferation and neurogenesis, and an increase in the synaptic protein, synaptophysin. Atorvastatin‐induced angiogenesis in a tube formation assay was reduced by an antibody against the vascular endothelial growth factor receptor 2 (FIK‐1) and by the nitric oxide synthase inhibitor, N‐mono‐methyl‐L‐arginine (L‐NAME). Atorvastatin also induced phosphorylation of Akt and Erk in cultured primary cortical neurons. These data indicate that atorvastatin induced brain plasticity and has neurorestorative activity after experimental stroke. Ann Neurol 2003
The spectrum of autoimmune autonomic neuropathies
Authors: Klein Caroline M. , Vernino Steven , Lennon Vanda A. , Sandroni Paola , Fealey Robert D. , Benrud‐Larson Lisa , Sletten David , Low Phillip A. 
Published: May 2003

AbstractWe analyzed the clinical characteristics of 18 patients (13 female, 5 male) who had autoimmune autonomic neuropathy (AAN) and ganglionic acetylcholine receptor (AChR) autoantibodies. Mean age was 61.4 years (standard deviation, 12.0 years). Ten patients had subacute symptom onset, six with an antecedent event. Eight patients had chronic AAN, characterized by insidious symptom onset, without antecedent event, and gradual progression. A majority of patients with high antibody values (>1.00 nmol/L) had a combination of sicca complex (marked dry eyes and dry mouth), abnormal pupillary light response, upper gastrointestinal symptoms, and neurogenic bladder. Chronic AAN segregated into two subgroups. One subgroup (N = 4) had low antibody titer (0.09 ± 0.01 nmol/L) and a paucity of cholinergic symptoms. It was indistinguishable from pure autonomic failure. The other subgroup (N = 4) had high antibody titer (11.6 ± 2.08 nmol/L), sicca complex, abnormal pupils, and neurogenic bladder; three had severe upper gastrointestinal dysfunction. Higher antibody titers correlated with greater autonomic dysfunction and more frequent cholinergic dysautonomia. These observations expand the clinical spectrum of AAN to include chronic cases, some being indistinguishable from pure autonomic failure, and support the concept that ganglionic AChR antibodies are important diagnostically and pathophysiologically in acquired dysautonomia.Ann Neurol 2003;53:752–758
Asymmetric flaccid paralysis: A neuromuscular presentation of West Nile virus infection
Authors: Li Jun , Loeb Jeffrey A. , Shy Michael E. , Shah Aashit K. , Tselis Alex C. , Kupski William J. , Lewis Richard A. 
Published: May 2003

AbstractThe neuromuscular aspects of West Nile virus (WNV) infection have not been characterized in detail. We have studied a group of six patients with proven WNV infection. All cases presented with acute, severe, asymmetric, or monolimb weakness, with minimal or no sensory disturbance after a mild flu‐like prodrome. Four cases also had facial weakness. Three of our cases had no encephalitic signs or symptoms despite cerebrospinal fluid pleocytosis. Electrophysiological studies showed severe denervation in paralyzed limb muscles, suggesting either motor neuron or multiple ventral nerve root damage. This localization is supported further by the finding of abnormal signal intensity confined to the anterior horns on a lumbar spine magnetic resonance imaging. Muscle biopsies from three patients showed scattered necrotic fibers, implicating mild direct or indirect muscle damage from the WNV infection. In summary, we describe a group of patients with acute segmental flaccid paralysis with minimal or no encephalitic or sensory signs. We have localized the abnormality to either the spinal motor neurons or their ventral nerve roots. It will be important for physicians to consider WNV infection in patients with acute asymmetric paralysis with or without encephalitic symptoms. Ann Neurol 2003;53:703–710
Altered hippocampal muscarinic receptors in acetylcholinesterase‐deficient mice
Authors: Volpicelli‐Daley Laura A. , Duysen Ellen G. , Lockridge Oksana , Levey Allan I. 
Published: May 2003

AbstractA primary therapeutic strategy for Alzheimer's disease includes acetylcholinesterase (AChE) inhibitors with the goal of enhancing cholinergic transmission. Stimulation of muscarinic acetylcholine receptors (mAChRs) by elevated levels of ACh plays a role in the effects of AChE inhibitors on cognition and behavior. However, AChE inhibitors only demonstrate modest symptomatic improvements. Chronic treatment with these drugs may cause mAChR downregulation and consequently limit the treatment efficacy. AChE knockout (−/−) mice were utilized in this study as a model for investigating the effects of selective, complete, and chronic diminished AChE activity on mAChR expression and function. In AChE −/− mice, the M1, M2, and M4 mAChRs showed strikingly 50 to 80% decreased expression in brain regions associated with memory. In addition, mAChRs showed decreased presynaptic, cell surface, and dendritic distributions and increased localization to intracellular puncta. Furthermore, mAChR agonist–induced activation of extracellular signal–regulated kinase, a signaling pathway associated with synaptic plasticity and amyloidogenesis, is diminished in the hippocampus and cortex of AChE −/− mice. Therefore, chronic diminished ACh metabolism produces profound effects on mAChR expression and function. The alterations of mAChRs in AChE −/− mice suggest that mAChR downregulation may contribute to the limited efficacy of AChE inhibitors in Alzheimer's disease treatment. Ann Neurol 2003;53:788–796
Effect of ultrasound on thrombolysis of middle cerebral artery occlusion
Authors: Eggers Jürgen , Koch Björn , Meyer Karsten , König Inke , Seidel Günter 
Published: May 2003

AbstractWe studied the effect of transcranial 2MHz Doppler ultrasound (US) on the recanalization and outcome of stroke patients suffering from acute middle cerebral artery occlusion. All patients underwent intravenous recombinant tissue‐type plasminogen activator thrombolysis. Eleven patients were randomly selected for continuous US monitoring (C‐US) over 1 hour; 14 patients were selected for the control group. The C‐US group showed a higher grade of recanalization after 1 hour but also a higher number of intraparenchymal bleedings. Overall, a favorable functional outcome occurred more frequently in the C‐US group (Barthel index, p = 0.037) after 3 months. Ann Neurol 2003;53:797–800
Mitochondrial dysfunction in autistic patients with 15q inverted duplication
Authors: Filipek Pauline A. , Juranek Jenifer , Smith Moyra , Mays Lee Z. , Ramos Erica R. , Bocian Maureen , Masser‐Frye Diane , Laulhere Tracy M. , Modahl Charlotte , Spence M. Anne , Gargus J. Jay 
Published: May 2003

AbstractTwo autistic children with a chromosome 15q11‐q13 inverted duplication are presented. Both had uneventful perinatal courses, normal electroencephalogram and magnetic resonance imaging scans, moderate motor delay, lethargy, severe hypotonia, and modest lactic acidosis. Both had muscle mitochondrial enzyme assays that showed a pronounced mitochondrial hyperproliferation and a partial respiratory chain block most parsimoniously placed at the level of complex III, suggesting candidate gene loci for autism within the critical region may affect pathways influencing mitochondrial function. Ann Neurol 2003;53:801–804
Regular exercise is beneficial to a mouse model of amyotrophic lateral sclerosis
Authors: Kirkinezos Ilias G. , Hernandez Dayami , Bradley Walter G. , Moraes Carlos T. 
Published: May 2003

AbstractWe tested whether a regular exercise regimen was associated with a change in the life span of G93A‐SOD1 transgenic mice, a model of familial ALS. Regular treadmill running for 10 weeks led to a significant increase in the life span of G93A‐SOD1 mice. The effect was stronger in male mice, whereas there was only a trend between exercised and sedentary female G93A‐SOD1 mice. The data suggest that regular exercise has a beneficial effect on the progression of ALS. Ann Neurol 2003;53:804–807
Apolipoprotein C‐II deficiency presenting as a lipid encephalopathy in infancy
Authors: Wilson Callum J. , Oliva Claudio Priore , Maggi Franco , Catapano Alberico L. , Calandra Sebastiano 
Published: May 2003

AbstractAn infant presented with massive hyperchylomicronemia and a severe encephalopathy. MRI showed marked lipid deposition throughout the brain. Despite the normalization of the biochemistry, there was little clinical improvement, and at 18 months of age she has severe developmental delay, a strikingly abnormal MRI. Apolipoprotein C‐II, the lipoprotein on chylomicrons responsible for the activation of lipoprotein lipase, was not detectable in blood. Analysis of the APO C‐II gene revealed a novel homozygous point mutation, 1118C→A. Subsequently, another sibling has been born with the same homozygous mutation and similar biochemistry but, perhaps because of early treatment, a normal neurological outcome. Ann Neurol 2003;53:807–810
Healthy‐side dominance of cortical neuromagnetic responses in sudden hearing loss
Authors: Po‐Hung Li Lieber , Shiao An‐Suey , Lin Yung‐Yang , Chen Li‐Fen , Niddam David M. , Chang Shyue‐Yih , Lien Chiang‐Feng , Chou Nan‐San , Ho Low‐Tone , Hsieh Jen‐Chuen 
Published: May 2003

AbstractPrevious brain imaging and mapping studies have reported findings indicating functional reorganization in the central auditory pathways of patients with profound unilateral hearing loss. This study reports for the first time to our knowledge, using a whole‐head neuromagnetometer with monaural stimulation of both intact and affected ears, a pattern of healthy‐side dominance for cortical neuromagnetic responses in adult patients in the early stage of idiopathic sudden sensorineural hearing loss, and a pattern of contralateral dominance is verified in controls. Ann Neurol 2003;53:810–815
Antiepileptic drugs as a possible neuroprotective strategy in brain ischemia
Authors: Calabresi Paolo , Cupini Letizia M. , Centonze Diego , Pisani Francesco , Bernardi Giorgio 
Published: May 2003

AbstractSeveral new antiepileptic drugs (AEDs) have been introduced for clinical use recently. These new AEDs, as did the classic AEDs, target multiple cellular sites both pre‐ and postsynaptically. The major common goal of the pharmacological treatment using AEDs is to counteract abnormal brain excitability by either decreasing excitatory transmission or enhancing neuronal inhibition. Interestingly, an excessive release of excitatory amino acids and a reduced neuronal inhibition also occur in brain ischemia. Thus, recently, the use of AEDs as a possible neuroprotective strategy in brain ischemia is receiving increasing attention, and many AEDs have been tested in animal models of stroke, providing encouraging results. Experimental studies utilizing global or focal ischemia in rodents have provided insights into the possible neuroprotective action of the various AEDs. However, the implication of these studies in the treatment of acute stroke in humans is not always direct. In fact, various clinical studies with drugs targeting the same voltage‐ and ligand‐gated channels modulated by most of the AEDs failed to show neuroprotection. The differential mechanisms that underlie the development of focal ischemic injury in experimental animal models versus human stroke require further investigation to open a new therapeutic perspective for neuroprotection that might be applicable in the future. Ann Neurol 2003;53:693–702
N19S, a new SOD1 mutation in sporadic amyotrophic lateral sclerosis: No evidence for disease causation
Authors: Mayeux Véronique , Corcia Philippe , Besson Gérard , Jafari‐Schluep Hélène‐Farnase , Briolotti Valérie , Camu William ,   the French ALS Research Group
Published: May 2003

AbstractIn a group of 331 sporadic amyotrophic lateral sclerosis (ALS) cases, we identified a new Cu/Zn superoxide dismutase single base substitution, N19S, in two patients. In the first case, seven healthy family members of 15 carried the substitution. Controls (n = 268) and familial ALS index cases (n = 180) were screened and one control subject with N19S was identified. Our data show that, despite a possible role of susceptibility factor for ALS, N19S alone cannot be considered as a direct cause for the disease. Ann Neurol 2003;53:815–818
Elevated osteopontin levels in active relapsing‐remitting multiple sclerosis
Authors: Vogt Mario H. J. , Lopatinskaya Luba , Smits Monique , Polman Chris H. , Nagelkerken Lex 
Published: May 2003

AbstractIn the search for proteins that might play a role in the pathogenesis of multiple sclerosis (MS), osteopontin (OPN) has been identified as the most prominent cytokine‐encoding gene expressed within MS lesions. Here, we report significantly increased OPN protein levels in plasma of relapsing‐remitting MS patients. In contrast, OPN protein levels in primary progressive and secondary progressive MS patients were similar to healthy control levels. Interestingly, active relapsing‐remitting patients had higher OPN protein levels than patients without relapses. Ann Neurol 2003;53:819–822
Polyamide‐reinforced ethylene–propylene–diene rubber compatibilized with chlorinated polyethylene
Authors: Liu Xin , Huang Hua , Zhang Yong , Zhang Yinxi 
Published: May 2003

AbstractVulcanizates of blends of ethylene–propylene–diene rubber and polyamide copolymers were prepared by reactive compatibilization. A reactive route was employed for compatibilizing these blends with the addition of chlorinated polyethylene (CPE). The influence of the compatibilizers, crosslinking agents, blend compositions, and addition modes of the compatibilizers on the mechanical properties of the blends was investigated. The morphologies of the blends were determined with scanning electron microscopy. The addition of CPE was found to reduce the particle size of the dispersed phase remarkably. The stability of the blends with compatibilizers was measured by high‐temperature thermal aging. The mechanical properties were examined by stress–strain measurements and dynamic mechanical thermal measurements; the addition of polyamide copolymers caused significant improvements in the tensile properties of these blends.© 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1727–1736, 2003
Examination of selected synthesis and room‐temperature storage parameters for wood adhesive‐type urea–formaldehyde resins by 13C‐NMR spectroscopy. V
Authors: Kim Moon G. , Young No B. , Lee Sang M. , Nieh World L. 
Published: May 2003

AbstractThe effects of posttreatments of particleboard adhesive‐type urea–formaldehyde resins were studied. The resins were synthesized with formaldehyde/first urea (F/U1) mol ratios of 1.40, 1.60, 1.80, 2.10, and 2.40 and then the second urea was added to give a final formaldehyde/urea ratio of 1.15 in alkaline pH. The resins were posttreated at 60°C for up to 13.5 h and the 2.5‐h heat‐treated resin samples were stored at room temperature for up to 27 days. Resins sampled during the posttreatments were examined by 13C‐NMR and evaluated by bonding particleboards. In the posttreatments, hydroxymethyl groups on the polymeric resin components dissociated to formaldehyde and reacted with the second urea, and methylene and methylene–ether groups were formed from reactions involving the second urea. Methylene–diurea and urea groups bonded to UF polymers were identified. As a result, the viscosity of the resins initially decreased but later increased along with the cloudiness of the resins. Bond‐strength and formaldehyde‐emission values of particleboard varied with posttreatment variables as well as with the F/U1 mol ratios used in the resin syntheses. The results would be useful in optimizing resin synthesis and handling parameters. Various reaction mechanisms were considered. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1896–1917, 2003
Highly filled blends of a vinylic copolymer with plasticized lignin: Thermal and mechanical properties
Authors: Feldman D. , Banu D. , Manley R. St. J. , Zhu H. 
Published: May 2003

AbstractThe objective of this study was the development of new vinyl flooring formulations with increased resistance to attack by fungi and microorganisms, formulated with plasticizers having chemical compositions different from that of common dioctyl phthalate (DOP). Alkyl phthalate plasticizers are considered to be toxicological and ecotoxicological hazards, although this is still under debate. It is suspected that during the service life of poly(vinyl chloride) (PVC) flooring, the attack of fungi and microorganisms leads to the degradation of DOP and the release of some volatile organic compounds. For this reason, in the new flooring formulations, the vinyl chloride/vinyl acetate copolymer (VC–VAc) was partially replaced with lignin, a natural polymer and a major component of wood and vascular plants. Besides its other functions in wood, lignin imparts resistance to microorganisms. An organosolv lignin from Alcell Technologies, Inc. (AL), was used as a partial replacement of PVC. The influence of the new plasticizers, as well as the influence of the partial replacement of VC–VAc with lignin, on the morphology and thermal and mechanical properties of the composites was investigated with scanning electron microscopy, differential scanning calorimetry, and tensile testing. Butyl benzyl phthalate and diethylene glycol dibenzoate were used as plasticizers; both were compatible with PVC and AL. The results indicated that diethylene glycol dibenzoate was the best plasticizer for these blend composites. In these formulations, AL could replace up to 20 parts of the copolymer. At this level of replacement, the key mechanical properties of the new composites compared very favorably with those of the DOP control formulations. The obtained formulation will be tested further for resistance to fungi and microorganisms. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2000–2010, 2003
Synthesis of novel polyimides containing side‐chain azo‐2‐naphthol moieties
Authors: Mallakpour Shadpour , Hajipour Abdol‐Reza , Vahabi Ramin 
Published: May 2003

AbstractAn amine‐ester derivative of isoeugenol was prepared in three steps. This amine‐ester was converted to diazonium salt and subsequently was reacted with 2‐naphthol and a novel isoeugenol ester‐azo derivative as a new monomer was obtained in quantitative yield. This monomer was characterized by high‐field 1H‐NMR, IR, and elemental analysis and then was used for the preparation of model compound and polymerization reactions. 4‐Phenyl‐1,2,4‐triazoline‐3,5‐dione was allowed to react with this new monomer. The reaction was very fast and gave only one double adduct by Diels–Alder and ene pathways in excellent yield. The polymerization reactions of novel monomer with bistriazolinediones [bis(p‐3,5‐dioxo‐1,2,4‐triazolin‐4‐ylphenyl)methane and 1,6‐bis(3,5‐dioxo‐1,2,4‐triazolin‐4‐yl)hexane] were carried out in N,N‐dimethylacetamide at room temperature. The reactions were exothermic, fast, and gave novel heterocyclic polyimides by repetitive Diels–Alder‐ene polyaddition reactions. Some structural characterization and physical properties of these novel heterocyclic polyimides are reported. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1942–1951, 2003
Developmental skeletal anomalies
Authors: Morcuende Jose A. , Weinstein Stuart L. 
Published: May 2003

AbstractA genetic and molecular revolution is taking place in medicine today. Led by the Human Genome Project, genetic information and concepts are changing the way diseases are defined, diagnoses are made, and treatment strategies are developed. The profound implications of actually understanding the molecular abnormalities of many clinical problems are affecting virtually all medical and surgical disciplines. The ability to apply knowledge gleaned from the laboratory is our best hope for developing strategies to modify the pathologic effects of genes (by drug therapy), repair genes (gene therapy), and restore lost or affected tissues (tissue engineering). Instead of an empiric trial‐and‐error approach to therapy, it may become feasible to tailor treatment to the specific molecular malfunction. In this review we have chosen to emphasize a few selected musculoskeletal disorders, including skeletal dysplasias, spinal deformities, developmental dislocation of the hip, and idiopathic clubfoot. The logical extension of our understanding of the molecular players in many of these disorders is to establish precisely what the products of the affected genes do during skeletal development, and how mutations disturb these functions to produce the characteristic phenotype. Despite the many hypotheses generated from the work in human genetics, and the knowledge that has been gained from animal models, there remains a relatively poor understanding of how these genes interfere with skeletal development. Unraveling these mysteries and defining them in molecular and cellular terms will be the challenges for the near future. Birth Defects Research (Part C) 69:197–207, 2003. © 2003 Wiley‐Liss, Inc.
Physiology and pathophysiology of the growth plate
Authors: Ballock R. Tracy , O'Keefe Regis J. 
Published: May 2003

AbstractLongitudinal growth of the skeleton is a result of endochondral ossification that occurs at the growth plate. Through a sequential process of cell proliferation, extracellular matrix synthesis, cellular hypertrophy, matrix mineralization, vascular invasion, and eventually apoptosis, the cartilage model is continually replaced by bone as length increases. The regulation of longitudinal growth at the growth plate occurs generally through the intimate interaction of circulating systemic hormones and locally produced peptide growth factors, the net result of which is to trigger changes in gene expression by growth plate chondrocytes. This review highlights recent advances in genetics and cell biology that are illuminating the important regulatory mechanisms governing the structure and biology of the growth plate, and provides selected examples of how studies of human mutations have yielded a wealth of new knowledge regarding the normal biology and pathophysiology of growth plate cartilage. Birth Defects Research (Part C) 69:123–143, 2003. © 2003 Wiley‐Liss, Inc.
Molecular ontogeny of the skeleton
Authors: Eames B. Frank , De La Fuente Luis , Helms Jill A. 
Published: May 2003

AbstractFrom a traditional viewpoint, skeletal elements form by two distinct processes: endochondral ossification, during which a cartilage template is replaced by bone, and intramembranous ossification, whereby mesenchymal cells differentiate directly into osteoblasts. There are inherent difficulties with this historical classification scheme, not the least of which is that bones typically described as endochondral actually form bone through an intramembranous process, and that some membranous bones may have a transient chondrogenic phase. These innate contradictions can be circumvented if molecular and cellular, rather than histogenic, criteria are used to describe the process of skeletal tissue formation. Within the past decade, clinical examinations of human skeletal syndromes have led to the identification and subsequent characterization of regulatory molecules that direct chondrogenesis and osteogenesis in every skeletal element of the body. In this review, we survey these molecules and the tissue interactions that may regulate their expression. What emerges is a new paradigm, by which we can explain and understand the process of normal –and abnormal‐ skeletal development. Birth Defects Research (Part C) 69:93–101, 2003. © 2003 Wiley‐Liss, Inc.