bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol consumption and the incidence of Parkinson's disease
Authors: Hernán Miguel A. , Chen Honglei , Schwarzschild Michael A. , Ascherio Alberto 
Published: July 2003

AbstractCigarette smoking and caffeine consumption are associated with a decreased incidence of Parkinson's disease (PD). This inverse association may result from neuroprotective effects of cigarette smoke and caffeine, or from a disinclination of future PD patients to engage in habituating behaviors. We investigated the association between consumption of alcoholic beverages, another potentially habituating behavior, and risk of PD in two large prospective cohorts Nurses' Health Study, and Health Professionals' Follow‐up Study. We detected 415 new cases of PD during follow‐up. Compared with nondrinkers at baseline, the relative rate (95% confidence interval) was 1.0 (0.8–1.3) for drinkers of less than 5gm/day, 1.0 (0.8–1.4) for 5 to less than 15gm/day, 1.1 (0.8–1.6) for 15 to less than 30gm/day, and 0.7 (0.5–1.2) for 30gm/day or more (p for trend = 0.45). Consumption of wine or liquor was not associated with the incidence of PD. Compared with those who consumed beer less than once per month, the relative rate (95% confidence interval) was 0.7 (0.5–0.9) for one to three drinks of beer per month, and 0.7 (0.5, 0.9) for one or more drinks of beer per week. The risk of PD was similar in individuals who usually consume moderate amounts of alcohol and in abstainers. Ann Neurol 2003
Neuronal overexpression of cyclooxygenase‐2 increases cerebral infarction
Authors: Doré Sylvain , Otsuka Takashi , Mito Toshiaki , Sugo Nubuo , Hand Tracey , Wu Liejun , Hurn Patricia D. , Traystman Richard J. , Andreasson Katrin 
Published: July 2003

AbstractIncreases in COX‐2 enzymatic activity and prostaglandin production have been associated with neuronal injury in both acute and age‐related degenerative neurological diseases. In this study, we tested the effects of increased COX‐2 activity in a model of transient focal ischemia using a transgenic mouse model in which human COX‐2 is constitutively expressed selectively in neurons of the striatum, cerebral cortex, and hippocampus. These COX‐2 transgenic mice harbor elevated levels of PGE2 that are 10‐fold higher than nontransgenic levels. A significant increase in infarct volume was observed after middle cerebral artery occlusion with 4 days of reperfusion in COX‐2 transgenic mice as compared with nontransgenic littermates. Pretreatment of nontransgenic mice with the selective COX‐2 inhibitor SC58236 resulted in a significant reduction of infarct volume in nontransgenic mice, consistent with previous pharmacological studies. However, transgenic COX‐2 mice treated with SC58236 did not show a significant reduction. This suggests that chronic increases in COX‐2 expression and enzymatic activity, which can occur in aging and in pathological states characterized by oxidative stress and chronic inflammatory processes, can lead to downstream cellular changes that have a negative impact on neuronal survival in cerebrovascular disease. Ann Neurol 2003
How much phenotypic variation can be attributed to parkin genotype?
Authors: Lohmann Ebba , Periquet Magali , Bonifati Vincenzo , Wood Nick W. , De Michele Giuseppe , Bonnet Anne‐Marie , Fraix Valérie , Broussolle Emmanuel , Horstink Martin W. I. M. , Vidailhet Marie , Verpillat Patrice , Gasser Thomas , Nicholl David , Teive Hélio , Raskin Salmo , Rascol Olivier , Destée Alain , Ruberg Merle , Gasparini Francesca , Meco Giuseppe , Agid Yves , Durr Alexandra , Brice Alexis ,   The French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease
Published: July 2003

AbstractTo establish phenotype–genotype correlations in early‐onset parkinsonism, we have compared the phenotype of a large series of 146 patients with and 250 patients without parkin mutations. Although no single sign distinguished the groups, patients with mutations had significantly earlier and more symmetrical onset, dystonia more often at onset and hyperreflexia, slower progression of the disease, and a tendency toward a greater response to levodopa despite lower doses. After forward stepwise multiple logistic regression analysis, dystonia at onset and brisk reflexes were not longer significantly different but were correlated with age at onset rather than the presence of the parkin mutation. Age at onset in carriers of parkin mutations varied as did the rate of progression of the disease: the younger the age at onset the slower the evolution. The genotype influenced the phenotype: carriers of at least one missense mutation had a higher United Parkinson's Disease Rating Scale motor score than those carrying two truncating mutations. The localization of the mutations was also important because missense mutations in functional domains of parkin resulted in earlier onset. Patients with a single heterozygous mutation had significantly later and more asymmetrical onset and more frequent levodopa‐induced fluctuations and dystonia than patients with two mutations. Ann Neurol 2003
Minocycline and doxycycline are not beneficial in a model of Huntington's disease
Authors: Smith Donna L. , Woodman Benjamin , Mahal Amarbirpal , Sathasivam Kirupa , Ghazi‐Noori Shabnam , Lowden Philip A. S. , Bates Gillian P. , Hockly Emma 
Published: July 2003

AbstractHuntington's Disease (HD) is an inherited neurological disorder causing movement impairment, personality changes, dementia, and premature death, for which there is currently no effective therapy. The modified tetracycline antibiotic, minocycline, has been reported to ameliorate the disease phenotype in the R6/2 mouse model of HD. Because the tetracyclines have also been reported to inhibit aggregation in other amyloid disorders, we have investigated their ability to inhibit huntingtin aggregation and further explored their efficacy in preclinical mouse trials. We show that tetracyclines are potent inhibitors of huntingtin aggregation in a hippocampal slice culture model of HD at an effective concentration of 30μM. However, despite achieving tissue levels approaching this concentration by oral treatment of R6/2 mice with minocycline, we observed no clear difference in their behavioral abnormalities, or in aggregate load postmortem. In the light of these new data, we would advise that caution be exercised in proceeding into human clinical trials of minocycline. Ann Neurol 2003
Quantification of myelinated endings and mechanoreceptors in human digital skin
Authors: Nolano Maria , Provitera Vincenzo , Crisci Claudio , Stancanelli Annamaria , Wendelschafer‐Crabb Gwen , Kennedy William Robert , Santoro Lucio 
Published: July 2003

AbstractWe used immunohistochemistry and confocal microscopy applied to fingertip punch biopsy to study glabrous skin innervation in 14 healthy subjects. In addition to epidermal nerve fibers, we quantified mechanoreceptors and their myelinated afferents. Using digital images and dedicated software, we calculated caliber, internodal and nodal length, and G‐ratio of the last four internodes of the myelinated endings. In our skin samples, we found a mean density of 59.0 ± 29.3 myelinated endings per square millimeter with a mean diameter of 3.3 ± 0.5μm and an internodal length of 79.1 ± 13.8μm. These findings indicate that Aβ fibers undergo drastic changes in their course from the nerve trunk to the target organ, with repeated branching and consequent tapering and shortening of internodal length. Our work demonstrates that skin biopsy can give information on the status of large myelinated endings as well as unmyelinated sensory and autonomic nerves. Since distal endings are primarily involved in distal axonopathy, skin biopsy can be more suitable than sural nerve biopsy to detect early abnormalities. In addition to diagnostic applications, this technique allows clarification of the mode of termination of Aβ fibers and their relationship with mechanoreceptors, leading to relevant electrophysiological speculations. Ann Neurol 2003
Toward a molecular neuropsychiatry of neurodegenerative diseases
Authors: Cummings Jeffrey L. 
Published: July 2003

AbstractQuantitative neuropsychiatry has provided increasingly precise descriptions of behavioral phenotypes associated with neurodegenerative disorders. Degenerative diseases of the brain are disturbances of protein metabolism, with failure of protein degredation by the ubiquitin‐proteosome system, production of neurotoxic peptide oligomers, and accumulation of intracellular protein deposits. Abnormalities of amyloid beta peptide, alpha‐synuclein protein, and hyperphosphorylated tau protein account for more than 90% of degenerative dementias. Functionally related neuroanatomical systems have shared metabolic characteristics and common vulnerabilities to protein dysmetabolism, providing the basis for phenotypes that reflect the underlying proteotype. Patients with alpha‐synuclein disorders are particularly prone to hallucinations, delusions, and rapid eye movement sleep behavior disorder. Patients with tauopathies manifest disproportionate disinhibition and apathy, and may exhibit compulsions. Alzheimer's disease is a triple proteinopathy with abnormalities of A‐beta, tau, and alpha‐synculein leading to a complex behavioral phenotype. This molecular approach to neuropsychiatry may assist in understanding the mechanisms of degenerative diseases, provide insight into the pathophysiology of neuropsychiatric symptoms, and contribute to monitoring disease‐modifying therapies. Ann Neurol 2003
Olfactory biopsies demonstrate a defect in neuronal development in Rett's syndrome
Authors: Ronnett Gabriele V. , Leopold Donald , Cai Xiaohe , Hoffbuhr Kristen C. , Moses Linda , Hoffman Eric P. , Naidu Sakkubai 
Published: July 2003

AbstractRett's Syndrome (RTT) is a neurodevelopmental disorder resulting from mutation in the mecp2 gene that encodes methyl CpG binding protein 2, a transcriptional repressor. Because this disease primarily affects neurons, tissue is not available during active disease. We used the olfactory system as a model to investigate abnormalities in neuronal development in RTT, because olfactory receptor neurons (ORNs) are replaced throughout life by ongoing postnatal neurogenesis. Thus, even in the adult, the olfactory epithelium contains neurons at various developmental stages. We obtained biopsies of nasal epithelium containing ORNs from RTT patients and age‐matched controls to study the status of the neuronal population using antibodies to stage‐specific developmental markers. There were no postprocedure complications. Compared with age‐matched controls, there were far fewer mature ORNs, as defined by olfactory marker protein expression, and significantly greater numbers of immature neuron‐specific tubulin–positive ORNs present. In RTT biopsies, olfactory marker protein–positive neurons displayed abnormal structure. These results suggest that dysfunction of MeCP2 results in decreased survival of mature ORNs with a compensatory increase in neurogenesis, or a failure of immature neurons to mature. Our study indicates that olfactory biopsies provide a method to study neuronal developmental diseases in adults and children. Ann Neurol 2003
Anticonvulsant properties of acetone, a brain ketone elevated by the ketogenic diet
Authors: Likhodii Sergei S. , Serbanescu Irina , Cortez Miguel A. , Murphy Patricia , Snead O. Carter , Burnham W. McIntyre 
Published: July 2003

AbstractThe ketogenic diet (KD), a treatment for drug‐resistant epilepsy, elevates brain acetone. Acetone has been shown to suppress experimental seizures. Whether elevation of acetone is the basis of the anticonvulsant effects of the KD and whether acetone, like the KD, antagonizes many different types of seizures, however, is unknown. This study investigated the spectrum of the anticonvulsant effects of acetone in animal seizure models. Rats were injected with acetone intraperitoneally. Dose–response effects were measured in four different models: (1) the maximal electroshock test, which models human tonic‐clonic seizures; (2) the subcutaneous pentylenetetrazole test, which models human typical absence seizures; (3) the amygdala kindling test, which models human complex partial seizures with secondary generalization; and (4) the AY‐9944 test, which models chronic atypical absence seizures, a component of the Lennox–Gastaut syndrome. Acetone suppressed seizures in all of the models, with the following ED50's (expressed in mmol/kg): maximal electroshock, 6.6; pentylenetetrazole, 9.7; generalized kindled seizures, 13.1; focal kindled seizures, 26.5; AY‐9944, 4.0. Acetone appears to have a broad spectrum of anticonvulsant effects. These effects parallel the effects of the KD. Elevation of brain acetone therefore may account for the efficacy of the KD in intractable epilepsy. Ann Neurol 2003
Apolipoprotein Eε4 modifies Alzheimer's disease onset in an E280A PS1 kindred
Authors: Pastor Pau , Roe Catherine M. , Villegas Andrés , Bedoya Gabriel , Chakraverty Sumi , García Gloria , Tirado Victoria , Norton Joanne , Ríos Silvia , Martínez Maribel , Kosik Kenneth S. , Lopera Francisco , Goate Alison M. 
Published: July 2003

AbstractWe previously have identified a large kindred from Colombia in which Alzheimer's disease (AD) is caused by the E280A presenilin 1 (PS1) mutation. The objective of this study was to examine whether environmental and genetic factors are responsible for variation in the phenotypic expression of the E280A PS1 mutation. We genotyped coding and promoter polymorphisms of the APOE gene in carriers of the E280A PS1 mutation. Kaplan–Meier product‐limit and Cox proportional hazard models were used in the statistical analyses. DNA was available from 114 carriers of the E280A PS1 mutation, including 52 subjects with AD. APOE ε4 allele carriers were more likely to develop AD at an earlier age than subjects without the ε4 allele (hazard ratio, 2.07; 95% confidence interval, 1.07–3.99; p = 0.030). Subjects with low education were more likely to develop AD later than those with higher education (hazard ratio, 0.476; 95% confidence interval, 0.26–0.87). Low educational level was associated with rural residence (p < 0.001). Promoter APOE variants did not influence either the onset or the duration of the disease. This study is the first to our knowledge to demonstrate that genetic and environmental factors influence age of onset in a kindred with a familial AD mutation. Ann Neurol 2003
Benign hereditary chorea: Clinical, genetic, and pathological findings
Authors: Kleiner‐Fisman Galit , Rogaeva Ekaterina , Halliday William , Houle Sylvain , Kawarai Toshitaka , Sato Christine , Medeiros Helena , St. George‐Hyslop Peter H. , Lang Anthony E. 
Published: July 2003

AbstractBenign hereditary chorea is an autosomal dominant disorder presenting with childhood‐onset chorea, no dementia, and little or no progression. We present a family with typical clinical features of benign hereditary chorea. Pathological investigation of the brain of an affected family member who died of an unrelated condition showed no significant gross or histological abnormalities. Genetic evaluation showed a novel single nucleotide substitution of intron 2 of the TITF‐1 gene (also referred to as TTF, NKX2.1, and T/ebp) on chromosome 14 which is predicted to have drastic consequences on the maturation processes of TITF‐1. Ann Neurol 2003
Increased Alzheimer pathology in Parkinson's disease related to antimuscarinic drugs
Authors: Perry Elaine K. , Kilford Linda , Lees Andrew J. , Burn David J. , Perry Robert H. 
Published: July 2003

AbstractThe hypothesis that blockade of muscarinic receptors is associated with increased Alzheimer‐type pathology was investigated in Parkinson's disease. Amyloid plaque densities were more than 2.5‐fold higher in cases treated with antimuscarinic medication in the long term compared with untreated or short‐term treated cases (p = 0.005 and 0.00005, respectively). Neurofibrillary tangle densities were also highest in chronic compared with untreated or acute‐treated groups (p = 0.02 and 0.05, respectively). The findings, if replicated, have potential implications for the use of anticholinergic medication in elderly Parkinson's disease patients. Ann Neurol 2003
Frequency and mechanisms of stroke recurrence after cryptogenic stroke
Authors: Bang Oh Young , Lee Phil Hyu , Joo Sung Yeol , Lee Jin Soo , Joo In Soo , Huh Kyoon 
Published: July 2003

AbstractThe purpose of this study was to better understand the frequency and mechanisms of stroke recurrence after the stroke with no determined cause (NC). We prospectively studied consecutive patients with acute cerebral infarcts. We divided the patients into five groups (large artery disease [LAD], cardioembolism [CE], small artery disease [SAD], two or more causes [TMC], and NC) and registered recurrent strokes and prognosis for 1 year. Those in the NC group were compared with other subtypes. A total of 204 patients were included; 56 LAD, 22 CE, 62 SAD, 27 TMC, and 37 NC. During follow‐up, there were 7 deaths and 31 first recurrent strokes. Patients of the NC group showed a significantly higher rate (30%) of recurrent stroke than those of other subtypes (LAD 16%; CE 14%; SAD 2%), and it was associated with the existence of mild stenosis (≤50%) on relevant artery or the stenosis of greater than 50% on nonrelevant artery. Occlusive lesions other than significant stenosis of relevant artery may play an important role in the development of stroke recurrence in patients of the NC group. Therefore, from the therapeutic and prognostic point of view, the detection of such occlusive lesions in patients with cryptogenic stroke may be needed.Ann Neurol 2003
Tibial muscular dystrophy in a Belgian family
Authors: Van den Bergh Peter Y. K. , Bouquiaux Olivier , Verellen Christine , Marchand Sylvie , Richard Isabelle , Hackman P. , Udd Bjarne 
Published: July 2003

AbstractWe report a Belgian family with autosomal dominant, late‐onset, distal myopathy with selective foot extensor muscle involvement of the lower legs. Linkage to the tibial muscular dystrophy (TMD) locus 2q31 was not evident at first because of incomplete disease penetrance in a 50‐year‐old asymptomatic family member. An abnormal tibialis anterior muscle biopsy established her subclinical status and linkage of the family to the TMD locus. Mutation analysis showed a disease‐specific, heterozygous point mutation in the last exon, Mex6, of the titin gene. This is the third mutation found in TMD and the second European family with TMD outside the Finnish population, suggesting that titinopathies may occur in various populations. Ann Neurol 2003
Impaired glial glutamate transport in a mouse tuberous sclerosis epilepsy model
Authors: Wong Michael , Ess Kevin C. , Uhlmann Erik J. , Jansen Laura A. , Li Wen , Crino Peter B. , Mennerick Steven , Yamada Kelvin A. , Gutmann David H. 
Published: July 2003

AbstractExcessive astrocytosis in cortical tubers in tuberous sclerosis complex (TSC) suggests that astrocytes may be important for epileptogenesis in TSC. We previously demonstrated that astrocyte‐specificTsc1gene inactivation in mice (Tsc1cKO mice) results in progressive epilepsy. Here, we report that glutamate transporter expression and function is impaired inTsc1cKO astrocytes.Tsc1cKO mice exhibit decreased GLT‐1 and GLAST protein expression. Electrophysiological assays demonstrate a functional decrease in glutamate transport currents ofTsc1cKO astrocytes in hippocampal slices and astrocyte cultures. These findings suggest thatTsc1inactivation in astrocytes causes dysfunctional glutamate homeostasis, leading to seizure development in TSC. Ann Neurol 2003
No preferential loss of paternal 19q alleles in oligodendroglial tumors
Authors: Hartmann Christian , Mueller Wolf , Lass Ulrike , Stockhammer Florian , von Eckardstein Kajetan , Veelken Julian , Jeuken Judith , Wick Wolfgang , von Deimling Andreas 
Published: July 2003

AbstractRecently, exclusive loss of paternal 19q alleles in six of six oligodendrogliomas has been reported, indicating that parental imprinting plays a role in these tumors. We examined a series of 10 oligodendrogliomas and 3 oligoastrocytomas with allelic losses on 1p and 19q for the parental origin of the lost alleles. Ten cases lost paternal 1p alleles and 3 cases lost maternal alleles. For 19q, six cases had loss of paternal alleles and seven cases of had loss of maternal alleles. These random distributions do not support the hypothesis that parental imprinting accounts for inactivation of the putative oligodendroglioma tumor suppressor genes. Ann Neurol 2003
Myelination of a fetus with Pelizaeus–Merzbacher disease: Immunopathological study
Authors: Shiraishi Kazuhiro , Itoh Masayuki , Sano Kenji , Takashima Sachio , Kubota Takeo 
Published: July 2003

AbstractWe report an autopsied case of a 21‐gestational‐week fetus with duplication of the proteolipid protein (PLP) gene (PLP1). An immunohistochemical study, which can detect the specific expression of PLP, myelin basic protein, myelin‐associated glycoprotein, and platelet‐derived growth factor receptor α subunit in brain tissues, showed that the myelination was almost the same as that of age‐matched controls. This result suggests that the development and migration of the oligodendrocyte is normal in Pelizaeus–Merzbacher disease until midgestation. To our knowledge, this is the first report of the myelination of a fetus with duplication of the PLP1 gene.
β‐amyloid peptides in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease
Authors: Wiltfang Jens , Esselmann Hermann , Smirnov Alexander , Bibl Mirko , Cepek Lukas , Steinacker Petra , Mollenhauer Brit , Buerger Katharina , Hampel Harald , Paul Sabine , Neumann Manuela , Maler Manuel , Zerr Inga , Kornhuber Johannes , Kretzschmar Hans A. , Poser Sigrid , Otto Markus 
Published: July 2003

AbstractDecreased levels of β‐amyloid peptide 1‐42 (Aβ1‐42) in cerebrospinal fluid (CSF) are a characteristic feature of Alzheimer's disease (AD) but recently were also observed in Creutzfeldt–Jakob disease (CJD). We analyzed the CSF of patients with CJD, and AD and nondemented controls using a quantitative urea‐based Aβ sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblot. Like in AD and nondemented controls, we found a highly conserved pattern of carboxyterminally truncated Aβ1‐37/38/39 in addition to Aβ1‐40/42 also in CJD patients. By the introduction of the ratio Aβ1‐39 to Aβ1‐42, CJD and AD can effectively be differentiated. We conclude that the immunoblot shows disease‐specific CSF Aβ peptide patterns in CJD and AD and suppose that measurement of the Aβ peptide pattern seems to be a promising diagnostic tool in the differential diagnosis of dementias. Ann Neurol 2003;54:263–267
Herpesviruses in brains in Alzheimer's and Parkinson's diseases
Authors: Hemling Niina , Röyttä Matias , Rinne Juha , Pöllänen Paju , Broberg Eeva , Tapio Virpi , Vahlberg Tero , Hukkanen Veijo 
Published: July 2003

AbstractWe evaluated the association of HSV‐1, HHV‐6, and VZV with Alzheimer's disease (AD) and Parkinson's disease (PD). Brain specimens for viral DNA polymerase chain reaction represented 34 patients with AD, 40 with PD, and 40 controls. One AD patient (2.9%) was positive for HSV‐1 DNA, 88.2% for HHV‐6 DNA, and 26.5% for VZV DNA; 17.5% of PD patients were HSV‐1 DNA–positive and 75% HHV‐6–positive, whereas 40% had VZV DNA. Twenty‐five percent of the controls were positive for HSV‐1 DNA, 87.5% for HHV‐6, and 27.5% for VZV. HSV‐1, VZV, or HHV‐6 DNA in brains was no additional risk factor for AD.