bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure
Authors: Guilarte Tomás R. , Toscano Christopher D. , McGlothan Jennifer L. , Weaver Shelley A. 
Published: January 2003

AbstractLong‐term deficits in cognitive function are the principal effects of lead (Pb2+) exposure in children and can be modeled in experimental animals. Current therapeutic approaches in the treatment of childhood Pb2+ intoxication are not effective in reversing learning deficits once they have occurred. We report that environmental enrichment reverses long‐term deficits in spatial learning produced by developmental Pb2+ exposure in rats. Enhanced learning performance of Pb2+‐exposed animals reared in an enriched environment was associated with recovery of deficits in N‐methyl‐D‐aspartate receptor subunit 1 (NR1) mRNA and induction of brain‐derived neurotrophic factor (BDNF) mRNA in the hippocampus. The effect of environmental enrichment on NR1 and BDNF gene expression was specific to Pb2+‐exposed animals and was present in the absence of changes in the NR2B subunit of the N‐methyl‐D‐aspartate receptor, GluR1, αCamKII, or PSD‐95 gene expression measured in the same animals. Our findings demonstrate that the learning impairments and NR1 subunit mRNA deficits resulting from developmental Pb2+ exposure are reversible if the animals are provided with an enriched environment even after the exposure has occurred. We propose environmental enrichment as a basis for the treatment of childhood Pb2+ intoxication.
Treatment of refractory myasthenia: “Rebooting” with high‐dose cyclophosphamide
Authors: Drachman Daniel B. , Jones Richard J. , Brodsky Robert A. 
Published: January 2003

AbstractPatients with myasthenia gravis (MG) who do not respond to conventional immunotherapeutic agents, or cannot tolerate their side effects, are considered “refractory.” Ablation of the immune system followed by bone marrow transplant has been shown to cure experimental MG in rats. It is now known that immunoablative treatment with high‐dose cyclophosphamide does not damage hematopoietic “stem cells,” permitting repopulation of the immune system without bone marrow transplant. Recent evidence indicates that this treatment can induce durable remissions in autoimmune diseases. We treated three myasthenic patients, for whom treatment with thymectomy, plasmapheresis, and conventional immunotherapeutic agents failed, by using high‐dose cyclophosphamide (50mg/kg/day intravenously for 4 days) followed by granulocyte colony stimulating factor. All three patients tolerated the treatment well and have had marked improvement in myasthenic weakness, permitting reduction of immunosuppressive medication to minimal levels. Acetylcholine receptor (AChR) antibody levels decreased in two AChR antibody–positive patients, and anti–MuSK antibody levels decreased in one “AChR antibody–negative” patient. The patients have been followed for up to 3.5 years, with no recurrence of symptoms. High‐dose cyclophosphamide treatment appears to be an effective and safe treatment for selected patients with refractory MG. Further follow‐up of these and additional patients will be needed to determine whether the benefit is durable.
FK506 is neuroprotective in a model of antiretroviral toxic neuropathy
Authors: Keswani Sanjay C. , Chander Bani , Hasan Chiler , Griffin John W. , McArthur Justin C. , Hoke Ahmet 
Published: January 2003

AbstractAntiretroviral toxic neuropathy is the most common neurological complication of human immunodeficiency virus infection. This painful neuropathy not only affects the quality of life of human immunodeficiency virus–infected patients but also severely limits viral suppression strategies. We have developed an in vitro model of this toxic neuropathy to better understand the mechanism of neurotoxicity and to test potential neuroprotective compounds. We show that among the dideoxynucleosides, ddC appears to be the most neurotoxic, followed by ddI and then d4T. This reflects their potency in causing neuropathy. AZT, which does not cause a peripheral neuropathy in patients, does not cause significant neurotoxicity in our model. Furthermore, in this model, we show that the immunophilin ligand FK506 but not cyclosporin A prevents the development of neurotoxicity by ddC, as judged by amelioration of ddC‐induced “neuritic pruning,” neuronal mitochondrial depolarization, and neuronal necrotic death. This finding suggests a calcineurin‐independent mechanism of neuroprotection. As calcineurin inhibition underlies the immunosuppressive properties of these clinically used immunophilin ligands, this holds promise for the neuroprotective efficacy of nonimmunosuppressive analogs of FK506 in the prevention or treatment of antiretroviral toxic neuropathy. Ann Neurol 2003;53:000–000
Head cooling with mild systemic hypothermia in anesthetized piglets is neuroprotective
Authors: Tooley James R. , Satas Saulius , Porter Helen , Silver Ian A. , Thoresen Marianne 
Published: January 2003

AbstractHypothermia is potentially therapeutic in the management of neonatal hypoxic‐ischemic brain injury. However, not all studies have shown a neuroprotective effect. It is suggested that the stress of unsedated hypothermia may interfere with neuroprotection. We propose that selective head cooling (SHC) combined with mild total‐body hypothermia during anesthesia enhances local neuroprotection while minimizing the occurrence of systemic side effects and stress associated with unsedated whole‐body cooling. Our objective was to determine whether SHC combined with mild total‐body hypothermia while anesthetized for a period of 24 hours reduces cerebral damage in our piglet survival model of global hypoxia‐ischemia. Eighteen anesthetized piglets received a 45‐minute global hypoxic‐ischemic insult. The pigs were randomized either to remain normothermic or to receive SHC. We found that the severity of the hypoxic‐ischemic insult was similar in the SHC versus the normothermic group, and that the mean neurology scores at 30 and 48 hours and neuropathology scores were significantly better in the SHC group versus the normothermic group. We conclude that selective head cooling combined with mild systemic hypothermia and anesthesia is neuroprotective when started immediately after the insult in our piglet model of hypoxic‐ischemic encephalopathy. Ann Neurol 2003;53:000–000
Human lateral geniculate nucleus and visual cortex respond to screen flicker
Authors: Krolak‐Salmon Pierre , Hénaff Marie‐Anne , Tallon‐Baudry Catherine , Yvert Blaise , Guénot Marc , Vighetto Alain , Mauguière François , Bertrand Olivier 
Published: January 2003

AbstractThe first electrophysiological study of the human lateral geniculate nucleus (LGN), optic radiation, striate, and extrastriate visual areas is presented in the context of presurgical evaluation of three epileptic patients (Patients 1, 2, and 3). Visual‐evoked potentials to pattern reversal and face presentation were recorded with depth intracranial electrodes implanted stereotactically. For Patient 1, electrode anatomical registration, structural magnetic resonance imaging, and electrophysiological responses confirmed the location of two contacts in the geniculate body and one in the optic radiation. The first responses peaked approximately 40 milliseconds in the LGN in Patient 1 and 60 milliseconds in the V1/V2 complex in Patients 2 and 3. Moreover, steady state visual‐evoked potentials evoked by the unperceived but commonly experienced video‐screen flicker were recorded in the LGN, optic radiation, and V1/V2 visual areas. This study provides topographic and temporal propagation characteristics of steady state visual‐evoked potentials along human visual pathways. We discuss the possible relationship between the oscillating signal recorded in subcortical and cortical areas and the electroencephalogram abnormalities observed in patients suffering from photosensitive epilepsy, particularly video‐game epilepsy. The consequences of high temporal frequency visual stimuli delivered by ubiquitous video screens on epilepsy, headaches, and eyestrain must be considered.
New perspectives on developing acute stroke therapy
Authors: Fisher Marc , Ratan Rajiv 
Published: January 2003

AbstractThe development of additional acute stroke therapies to complement and supplement intravenous recombinant tissue‐type plasminogen activator within the first 3 hours after stroke onset remains an important and pressing need. Much has been learned about the presumed target of acute stroke therapy, the ischemic penumbra, and clinically available imaging modalities such as magnetic resonance imaging and computed tomography hold great promise for at least partially identifying this region of potentially salvageable ischemic tissue. Understanding the biology of ischemia‐related cell injury has also evolved rapidly. New treatment approaches to improve outcome after focal brain ischemia will likely be derived by looking at naturally occurring adaptive mechanisms such as those related to ischemic preconditioning and hibernation. Many clinical trials previously performed with a variety of neuroprotective and thrombolytic drugs provide many lessons that will help to guide future acute stroke therapy trials and enhance the likelihood of success in future trials. Combining knowledge from these three areas provides optimism that additional acute stroke therapies can be developed to maximize beneficial functional outcome in the greatest proportion of acute stroke patients possible.
Plasma and cerebrospinal fluid α1‐antichymotrypsin levels in Alzheimer's disease: Correlation with cognitive impairment
Authors: DeKosky Steven T. , Ikonomovic Milos D. , Wang Xiaoyan , Farlow Martin , Wisniewski Stephen , Lopez Oscar L. , Becker James T. , Saxton Judith , Klunk William E. , Sweet Robert , Kaufer Daniel I. , Kamboh M. Ilyas 
Published: January 2003

Abstractα‐1‐Antichymotrypsin (ACT) is present in neuritic plaques in which it participates in the inflammatory cascade of Alzheimer's disease (AD). Reports of blood ACT levels in AD, and its usefulness as a disease biomarker, have been conflicting. In an effort to clarify this, we measured plasma ACT levels in 516 white subjects including 359 subjects with probable or possible AD, 44 subjects with other late‐life dementias, and 113 nondemented people. Subjects with systemic inflammatory diseases or who were taking antiinflammatory medications were excluded. All patients underwent extensive medical and detailed neuropsychological examinations at the time their blood was drawn. We found that plasma ACT levels were elevated in AD patients compared with the control group (p = 0.01) and were associated with severity of AD dementia; there was a negative association with the Mattis Dementia Rating Scale (a global measure of cognition) and a positive association with the Clinical Dementia Rating Scale (a global functional assessment). These relationships remained significant after controlling for demographic and genetic variables. When AD subjects were stratified into subgroups by dementia severity, matched by age, education, and gender, increased serum ACT correlated with Clinical Dementia Rating Scale (p = 0.0041) or Mattis Dementia Rating Scale (p = 0.0031) scores. ACT measurements in cerebrospinal fluid from an additional 34 AD cases and 16 controls showed elevated levels (p = 0.02) in AD. There was a negative correlation (p = 0.037) between cerebrospinal fluid ACT levels and clinical severity as measured by the Mini‐Mental State Examination. Our results demonstrate that peripheral ACT levels are elevated in AD, but not in dementias other than AD, and they increase with progression of AD dementia. Although not useful as a diagnostic biomarker, ACT may reflect disease severity and may be helpful as a within subject biomarker in interventions (particularly with antiinflammatory agents) directed at slowing or halting progression of disease.
Correlation between extracellular glucose and seizure susceptibility in adult rats
Authors: Schwechter Evan M. , Velís̆ková Jana , Velís̆ek Libor 
Published: January 2003

AbstractIn adult diabetic patients, periods of hyperglycemia may be associated with exacerbation of focal seizures. Our objective was to determine in the adult rats the correlation between seizure susceptibility and extracellular glucose concentration in two models of seizures. Male rats were injected with two doses of streptozocin (40mg/kg IP) on 2 consecutive days to induce diabetic hyperglycemia. Controls either received vehicle or were not injected. After 2 weeks, blood glucose concentration was measured, and the rats were subjected to flurothyl seizure test. Another group of rats received glucose solution (20%, 5ml IP) 30 minutes before testing to induce nondiabetic hyperglycemia. Thresholds for flurothyl‐induced clonic and tonic‐clonic seizures were determined. Finally, in vitro epileptiform activity was induced in the entorhinal cortex‐hippocampal slices from naive rats by perfusing with magnesium‐free medium with various glucose concentrations. In additional slices, paired‐pulse paradigm was determined in the perforant path. Susceptibility to clonic and tonic‐clonic flurothyl‐induced seizures positively correlated with blood glucose concentrations as the increased glucose concentration was associated with proconvulsant effects. Similarly, in the in vitro experiments, epileptiform activity was promoted by increased and suppressed by decreased glucose concentrations. Data indicate that, in the adult rats, high glucose concentrations are associated with proconvulsant effects.
Motor cortex excitability in Alzheimer's disease: A transcranial magnetic stimulation study
Authors: Ferreri Florinda , Pauri Flavia , Pasqualetti Patrizio , Fini Rita , Dal Forno Gloria , Rossini Paolo Maria 
Published: January 2003

AbstractMotor deficits affect patients with Alzheimer's disease only at later stages. Recent studies demonstrate that the primary motor cortex is affected by neuronal degeneration accompanied by the formation of amyloid plaques and neurofibrillary tangles. It is conceivable that neuronal loss is compensated by reorganization of the neural circuitries occurring along the natural course of the disease, thereby maintaining motor performances in daily living. Cortical motor output to upper limbs was tested via motor‐evoked potentials from forearm and hand muscles elicited by transcranial magnetic stimulation of motor cortex in 16 patients with mild Alzheimer's disease without motor deficits. Motor cortex excitability was increased, and the center of gravity of motor cortical output, as represented by excitable scalp sites, showed a frontal and medial shift, without correlated changes in the site of maximal excitability (hot‐spot). This may indicate functional reorganization, possibly after the neuronal loss in motor areas. Hyperexcitability might be caused by a dysregulation of the intracortical GABAergic inhibitory circuitries and selective alteration of glutamatergic neurotransmission. Such findings suggest that motor cortex hyperexcitability and reorganization allows prolonged preservation of motor function during the clinical course of Alzheimer's disease.
Cardiac energetics correlates to myocardial hypertrophy in Friedreich's ataxia
Authors: Bunse Michael , Bit‐Avragim Nana , Riefflin Axel , Perrot Andreas , Schmidt Oliver , Kreuz Friedmar R. , Dietz Rainer , Jung Wulf‐Ingo , Osterziel Karl Josef 
Published: January 2003

AbstractFriedreich's ataxia is a neurodegenerative disease frequently associated with hypertrophic cardiomyopathy. We have determined mitochondrial ATP, phosphocreatine, and intracellular inorganic phosphate levels by 31P nuclear magnetic resonance spectroscopy in the heart of 11 Friedreich's ataxia patients and 11 healthy controls. For the first time, to our knowledge, we showed a significant correlation between the extent of myocardial energy deficiency and the degree of myocardial hypertrophy. When combining our results with previous works on Friedreich's ataxia, these novel findings suggest that energy metabolism is most likely the cause and hypertrophy the effect in Friedreich's ataxia. Ann Neurol 2003;53:000–000
The MAZ protein is an autoantigen of Hodgkin's disease and paraneoplastic cerebellar dysfunction
Authors: Bataller Luis , Wade Deborly F. , Graus Francesc , Rosenfeld Myrna R. , Dalmau Josep 
Published: January 2003

AbstractProbing a cerebellar expression library with TrAb sera from patients with Hodgkin's disease and paraneoplastic cerebellar degeneration resulted in the isolation of MAZ (myc‐associated zinc‐finger protein). Eleven of 19 TrAb sera and 16 of 131 controls reacted with MAZ, indicating a significant, although not specific, association between Tr and MAZ immunities (p < 0.001). Interestingly, 9 of 16 positive control patients also had cerebellar dysfunction. Purified MAZ antibodies reacted with Purkinje cells. In neuronal cells, MAZ interacts with DCC (Deleted in Colorectal Cancer product), the receptor for netrin‐1, a neuronal survival factor. These findings suggest epitope spreading between the Tr antigen and the MAZ–DCC complex and offer a possible model of immune‐mediated cerebellar disease. Ann Neurol 2003;53:000–000
Is the mitochondrial complex I ND5 gene a hot‐spot for MELAS causing mutations?
Authors: Liolitsa Danae , Rahman Shamina , Benton Sarah , Carr Lucinda J. , Hanna Michael G. 
Published: January 2003

AbstractWe identified two novel heteroplasmic mitochondrial DNA point mutations in the gene encoding the ND5 subunit of complex I: a 12770A→G transition identified in a patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes) and a 13045A→C transversion in a patient with a MELAS/Leber's hereditary optic neuropathy/Leigh's overlap syndrome. Biochemical analysis of muscle homogenates showed normal or very mildly reduced complex I activity. Histochemistry was normal. Our observations add to the evidence that mitochondrial ND5 protein coding gene mutations frequently associate with the MELAS phenotype, and it highlights the role of complex I dysfunction in MELAS. Ann Neurol 2003
A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique tau pathology
Authors: Kobayashi Tomonori , Ota Satoru , Tanaka Kuniaki , Ito Yuji , Hasegawa Masato , Umeda Yuri , Motoi Yumiko , Takanashi Masashi , Yasuhara Masahiro , Anno Midori , Mizuno Yoshikuni , Mori Hideo 
Published: January 2003

AbstractWe report a novel mutation of tau (L266V missense mutation in exon 9) which may cause a type of familial frontotemporal dementia. The brain of a patient showed Pick body–like inclusions and unique tau‐positive, argyrophilic astrocytes with stout filaments and naked, round, or irregular argyrophilic inclusions with deposits of both three‐repeat and four‐repeat tau. Recombinant tau with a L266V mutation showed a reduced ability to promote microtubule assembly, which may be the primary effect of the mutation. Ann Neurol 2003;53:000–000
Meningioma presenting with Cushing's syndrome: An unusual clinical presentation
Authors: Pecori Giraldi Francesca , Terreni Maria Rosa , Andreotti Claudia , Losa Marco , Lanzi Roberto , Pontiroli Antonio E. , Cavagnini Francesco 
Published: January 2003

AbstractWe report a patient with a meningioma presenting with Cushing's syndrome, an unprecedented paraneoplastic presentation. Molecular studies, bioassay, and high‐performance liquid chromatography of tumor specimens demonstrated the synthesis and secretion of bioactive corticotropin‐releasing hormone. To our knowledge, this appears to be the first report of a hormone‐secreting meningioma and, further, the first clearly proven case of Cushing's syndrome due to ectopic corticotropin‐releasing hormone secretion without concomitant corticotropin production. Ann Neurol 2003
Specialty polymeric membranes. XIV. Pervaporation of benzene/cyclohexane mixtures through modified polyamide membranes
Authors: Yoshikawa Masakazu , Matsumoto Masafumi , Igarashi Yutaka 
Published: January 2003

AbstractMethyl methacrylate, ethyl methacrylate, propyl methacrylate, and styrene were graft‐polymerized onto the amorphous polyamide poly(hexamethylene terephthalamide/isophthalamide) (SELAR). Membranes were prepared from the modified SELAR and unmodified SELAR. The membranes were permeated benzene in preference to cyclohexane from benzene/cyclohexane mixtures by pervaporation. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 183–188, 2003
Characterization to the weathering extent of LLDPE/LDPE thin film
Authors: Zhao B. Y. , Yi X. W. , Li R. Y. , Zhu P. F. , Hu K. A. 
Published: January 2003

AbstractA kind of LLDPE (linear low density polyethylene)/LDPE (low density polyethylene) thin film for farm applications was subjected to accelerated and natural weathering. Carbonyl group, melting point, tensile elastic modulus, and high‐temperature shearing modulus of weathered films were investigated as function of weathering time. Two kinds of carbonyl index, I1 and I2, which result from infrared spectroscopy (IR) spectra of the weathered films, were defined to characterize the weathering extent of the LLDPE/LDPE thin film. Based on I1 and I2, a correlation is made between the artificial and natural weathering of the film: 1 h of the artificial weathering is equivalent to about 10.73 h of the natural weathering. The difference between the accelerated weathering and the natural weathering was also discussed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 12–16, 2003
Friedrich Sigmund Merkel and his “Merkel cell”, morphology, development, and physiology: Review and new results
Authors: Halata Zdenek , Grim Milos , Bauman Klaus I. 
Published: January 2003

AbstractMerkel nerve endings are mechanoreceptors in the mammalian skin. They consist of large, pale cells with lobulated nuclei forming synapse‐like contacts with enlarged terminal endings of myelinated nerve fibers. They were first described by F.S. Merkel in 1875. They are found in the skin and in those parts of the mucosa derived from the ectoderm. In mammals (apart from man), the largest accumulation of Merkel nerve endings is found in whiskers. In all vertebrates, Merkel nerve endings are located in the basal layer of the epidermis, apart from birds, where they are located in the dermis. Cytoskeletal filaments consisting of cytokeratins and osmiophilic granules containing a variety of neuropeptides are found in Merkel cells. In anseriform birds, groups of cells resembling Merkel cells, with discoid nerve terminals between cells, form Grandry corpuscles. There has been controversy over the origin of Merkel cells. Results from chick/quail chimeras show that, in birds, Merkel cells are a subpopulation of cells derived from the neural crest, which thus excludes their development from the epidermis. Most recently, also in mammals, conclusive evidence for a neural crest origin of Merkel cells has been obtained. Merkel cells and nerve terminals form mechanoreceptors. Calcium ions enter Merkel cells in response to mechanical stimuli, a process which triggers the release of calcium from intracellular stores resulting in exocytosis of neurotransmitter or neuromodulator. Recent results suggest that there may be glutamatergic transmission between Merkel cell and nerve terminal, which appears to be essential for the characteristic slowly adapting response of these receptors during maintained mechanical stimuli. Thus, we are convinced that Merkel cells with associated nerve terminals function as mechanoreceptor cells. Cells in the skin with a similar appearance as Merkel cells, but without contact to nerve terminals, are probably part of a diffuse neuroendocrine system and do not function as mechanoreceptors. Probably these cells, rather than those acting as mechanoreceptors, are the origin of a highly malignant skin cancer called Merkel cell carcinoma. Anat Rec Part A 271A:225–239, 2003. © 2003 Wiley‐Liss, Inc.