bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine A2A Antagonist: A novel antiparkinsonian agent that does not provoke dyskinesia in Parkinsonian monkeys
Authors: Kanda Tomoyuki , Jackson Michael J. , Smith Lance A. , Pearce Ronald K. B. , Nakamura Joji , Kase Hiroshi , Kuwana Yoshihisa , Jenner Peter 
Published: January 2005

AbstractTreatment of Parkinson's disease with L‐dopa therapy leads to long‐term complications, including loss of drug efficacy and the onset of dyskinesia. Adenosine A2A receptors in striatum are selectively localized to GABAergic output neurons of the striato‐pallidal pathway and may avoid such problems. The novel adenosine A2A receptor antagonist KW‐6002 has been examined for antiparkinsonian activity in MPTP‐treated primates. Oral administration of KW‐6002 reversed motor disability in MPTP‐treated common marmosets in a dose‐dependent manner. However, KW‐6002 only modestly increased overall locomotor activity and did not cause abnormal movement, such as stereotypy. The ability of KW‐6002 to reverse motor disability was maintained on repeated daily administration for 21 days, and no tolerance was observed. KW‐6002 induced little or no dyskinesia in MPTP‐treated primates previously primed to exhibit dyskinesia by prior exposure to L‐dopa. These results suggest that selective adenosine A2A receptor antagonists represent a new class of antiparkinsonian agents that improve disability without producing hyperactivity and without inducing dyskinesia.
Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their recovery, in rats with moderate nigrostriatal lesions
Authors: Murer M. Gustavo , Dziewczapolski Gustavo , Menalled Liliana B. , García M. Carmen , Agid Yves , Gershanik Oscar , Raisman‐Vozari Rita 
Published: January 2005

AbstractOrally administered levodopa remains the most effective symptomatic treatment for Parkinson's disease (PD). The introduction of levodopa therapy is often delayed, however, because of the fear that it might be toxic for the remaining dopaminergic neurons and, thus, accelerate the deterioration of patients. However, in vivo evidence of levodopa toxicity is scarce. We have evaluated the effects of a 6‐month oral levodoapa treatment on several dopaminergic markers, in rats with moderate or severe 6‐hydroxydopamine‐induced lesions of mesencephalic dopamine neurons and sham‐lesioned animals. Counts of tyrosine hydroxylase (TH)‐immunoreactive neurons in the substantia nigra and ventral tegmental area showed no significant difference between levodopa‐treated and vehicle‐treated rats. In addition, for rats of the sham‐lesioned and severely lesioned groups, immunoradiolabeling for TH, the dopamine transporter (DAT), and the vesicular monoamine transporter (VMAT2) at the striatal level was not significantly defferent between rats treated with levodopa or vehicle. It was unexpected that quantification of immunoautoradiograms showed a partial recovery of all three dopaminergic markers (TH, DAT, and VMAT2) in the denervated territories of the striatum of moderately lesioned rats receiving levodopa. Furthermore, the density of TH‐positive fibers observed in moderately lesioned rats was higher in those treated chronically with levodopa than in those receiving vehicle. Last, that chronic levodopa administration reversed the up‐regulation of D2 dopamine receptors seen in severely lesioned rats provided evidence that levodopa reached a biologically active concentration at the basal ganglia. Our results demonstrate that a pharmacologically effective 6‐month oral levodopa treatment is not toxic for remaining dopamine neurons in a rat model of PD but instead promotes the recovery of striatal innervation in rats with partial lesions.
Pathogenesis of cortical myoclonus studied by magnetoencephalography
Authors: Mima Tatsuya , Nagamine Takashi , Ikeda Akio , Yazawa Shogo , Kimura Jun , Shibasaki Hiroshi 
Published: January 2005

AbstractMyoclonus‐associated cortical activities were studied by simultaneous recording of a magnetoencephalogram and an electroencephalogram in 6 patients with cortical myoclonus due to various causes. Cortical activities were averaged, with respect to the precise onset of the myoclonic jerk, to evaluate the myoclonus‐associated cortical magnetic fields. The estimated generator of their earliest peak was localized at the contralateral precentral gyrus in all patients. As judged from the direction of the electrical current, surface positive activity preceding the electromyographic discharge was detected in 3 patients with cortical reflex myoclonus and in 1 patients with possible corticobasal degeneration. In contrast, in the remaining 2 patients (Lennox‐Gastaut syndrome and Alzheimer's disease), magnetic fields time‐locked to the myoclonic jerk were associated with surface negative activity at the precentral cortex. The present study, applying for the first time an off‐line jerk‐locked back‐averaging analysis to magnetoencephalography, demonstrated the important role of the precentral cortex in generating spontaneous myoclonus. It is most likely that the differing polarity of the electromagnetic activity reflects the differing activation pattern within the cortical laminar structure in the precentral area, underlying the generation of various types of myoclonus.
Association between centromeric deletions of the SMN gene and sporadic adult‐onset lower motor neuron disease
Authors: Moulard Bruno , Salachas Francois , Chassande Bénédicte , Briolotti Valerie , Meininger Vincent , Malafosse Alain , Camu William 
Published: January 2005

AbstractThe telomeric copy (t) of the survival motor neuron (SMN) gene is homozygously deleted in more than 90% of patients with infantile motor neuron disease (MND). In the general population, no homozygous SMNt deletion has been found, whereas 5% of centromeric SMN (SMNc) deletions can be observed. Although SMNt deletions appear causal for infantile and at least some adult‐onset spinal muscular atrophy (SMA) (type IV), the respective role of SMN deletions remains unclear in adult‐onset MNDs. We studied SMN gene in three different groups of patients with adult‐onset MNDs. In sporadic amyotrophic lateral sclerosis (ALS; n = 177) ands familial ALS (n = 66), no SMNt deletion had been found, and the frequency of SMNc deletions was not increased. Converesly, among the 14 patients with sporadic pure lower MND (LMND), we found 2 patients with homozygous SMNt deletions (14%) and 5 patients with homozygous SMNc deletions (36%). These data suggest that (1) SMNt deletions do not account for the major part, if any, of adult‐onset LMND cases; and (2) SMNc deletions act as a susceptibility factor for LMNDs in adults. The clinical and gentic heterogeneity of LMND cases, including SMA type IV, are yet to be unexplained. Further studies on large groups of adult‐onset LMND patients are warranted to refine its nosology.
Hereditary form of parkinsonism—dementia
Authors: Muenter Manfred D. , Forno Lysia S. , Hornykiewicz Oleh , Kish Stephen J. , Maraganore Demetrius M. , Caselli Richard J. , Okazaki Haruo , Howard Frank M. , Snow Barry J. , Calne Donald B. 
Published: January 2005

AbstractIn four generations of a family, 13 members were afflicted with an autosomal dominant disorder characterized by young age at onset, early weight loss, and rapidly progressive dopa‐responsive parkinsonism, followed later by dementia and, in some, by hypotension. Intellectual dysfunction began with subjective memory loss and objective visuospatial dysfunction and was followed later by decline of frontal lobe cognitive and memory functions. Neuropathological examination in 4 autopsied cases showed neuronal loss in the substantia nigra and locus ceruleus and widespread Lewy bodies, many of them in the cerebral cortex; those in the hypothalamus and locus ceruleus were often of bizarre shapes. Other findings were vacuolation of the temporal cortex, unusual neuronal loss and gliosis in the hippocampus (CA 2/3), and neuronal loss in the nucleus basalis. There were no neuritic plaques, neurofibrillary tangles, or amyloid deposits. Positron emission tomography in 3 patients showed decreased striatal uptake of fluorodopa. Neurochemical analysis of an autopsied brain showed a pronounced decrease in choline acetyltransferase activity in the frontal and temporal cortices and hippocampus and a severe depletion of striatal dopamine with a pattern not typical of classic Parkinson's disease.
Beneficial effects of L‐serine and glycine in the management of seizures in 3‐phosphoglycerate dehydrogenase deficiency
Authors: de Koning Tom J. , Duran Marinus , Dorland Lambertus , Gooskens Rob , van Schaftingen Emile , Jaeken Jaak , Blau Nenad , Berger Ruud , Poll‐The Bwee Tien 
Published: January 2005

Abstract3‐Phosphoglycerate dehydrogenase (3‐PGDH) deficiency is an inborn error of serine biosynthesis. Patients are affected with congenital microcephaly, psychomotor retardation, and intractable seizures. The effects of oral treatment with amino acids were investigated in 2 siblings. L‐Serine up to 500 mg/kg/day was not sufficient for seizure control. Addition of glycine 200 mg/kg/day resulted in complete disappearance of seizures. Electroencephalographic abnormalities gradually resolved after 6 months. We conclude that 3‐PGDH can be treated effectively by a combination of L‐serine and glycine.
Familial spinocerebellar ataxia with cerebellar atrophy, peripheral neuropathy, and elevated level of serum creatine kinase, γ‐globulin, and α‐fetoprotein
Authors: Watanabe Mitsunori , Sugai Yoshiro , Concannon Patrick , Koenig Michel , Schmitt MichèLe , Sato Madoka , Shizuka Masami , Mizushima Kazuyuki , Ikeda Yoshio , Tomidokoro Yasushi , Okamoto Koichi , Shoji Mikio 
Published: January 2005

AbstractHere, we report a familial spinocerebellar ataxia (FSCA), which has clinical features similar to Friedreich's ataxia, an ataxia with isolated vitamin E deficiency, and ataxia telangiectasia. However, the serum levels of creatine kinase, γ‐globulin, and α‐fetoprotein were elevated, and biochemical and genetic analyses ruled out diagnosis of these three ataxias as well as other FSCAs. Thus, this family is thought to have a new type of FSCA.
Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease
Authors: Reiman Eric M. , Uecker Anne , Caselli Richard J. , Lewis Stephen , Bandy Daniel , De Leon Mony J. , De Santi Susan , Convit Antonio , Osborne David , Weaver Amy , Thibodeau Stephen N. 
Published: January 2005

AbstractBrain imaging techniques have the potential to characterize neurobiological changes that precede the onset of cognitive impairment in persons at risk for Alzheimer's disease. As previously described, positron emission tomography (PET) was used to compare 11 cognitively normal persons 50 to 62 years of age who were homozygous for the ε4 allele of apolipoprotein E and 22 persons without the ε4 allele with a reported family history of Alzheimer's dementia who were matched for sex, age, and level of education. The ε4 homozygotes had significantly reduced glucose metabolism in the same brain regions as patients with Alzheimer's dementia; the largest reduction was in the posterior cingulate cortex. As described here, magnetic resonance imaging (MRI) was used to compare hippocampal volumes in the same subject groups. The ε4 homozygotes showed nonsignificant trends for smaller left and right hippocampal volumes; overall, smaller hippocampal volumes were associated with reduced performance on a long‐term memory test. Whereas PET measurements of cerebral glucose metabolism begin to decrease before the onset of memory decline, MRI measurements of hippocampal volume begin to decrease in conjunction with memory decline in cognitively normal persons at risk for Alzheimer's disease.
Functional brain networks in DYT1 dystonia
Authors: Eidelberg David , Moeller James R. , Antonini Angelo , Kazumata Ken , Nakamura Toshitaka , Dhawan Vijay , Spetsieris Phoebe , DeLeon Deborah , Bressman Susan B. , Fahn Stanley 
Published: January 2005

AbstractEarly‐onset idiopathic torsion dystonia (ITD) is an autosomal dominant hyperkinetic movement disorder with incomplete penetrance, associated with a 3 base‐pair deletion in the DYT1 gene on chromosome 9q34. To determine the metabolic substrates of brain dysfunction in DYT1 dystonia, we scanned 7 nonmanifesting and 10 affected DYT1 carriers and 14 normal volunteers with [18F]fluorodeoxyglucose and positron emission tomography. We found that DYT1 dystonia is mediated by the expression of two independent regional metabolic covariance patterns. The first pattern, identified in an analysis of nonmanifesting gene carriers was designated movement free (MF). This abnormal pattern was characterized by increased metabolic activity in the lentiform nuclei, cerebellum, and supplementary motor areas. The MF pattern was present in DYT1 carriers with and without clinical manifestations and persisted in DYT1 dystonia patients in whom involuntary movements were suppressed by sleep. The second pattern, identified in an analysis of affected gene carriers with sustained contractions at rest, was designated movement related (MR). This pattern was characterized by increased metabolic activity in the midbrain, cerebellum, and thalamus. The expression of the MR pattern was increased in waking DYT1 patients with sustained dystonia, compared with DYT1 carriers who were unaffected or who had dystonia only on action, as well as normal controls. MR subject scores declined significantly with sleep in affected DYT1 patients but not in normal controls. These findings indicate the penetrance of the DYT1 gene is considerably greater than previously assumed. ITD is mediated through the interaction of functional brain networks relating separately to gene status and to abnormal movement.
Acquired idiopathic generalized anhidrosis with isolated sudomotor neuropathy
Authors: Miyazoe Seiji , Matsuo Hidenori , Ohnishi Akio , Tajima Fumihiro , Fujishita Satoshi , Ichinose Katsuhiro , Shibuya Noritoshi 
Published: January 2005

AbstractThe pathogenesis and underlying lesion of acquired idiopathic generalized anhidrosis (AIGA) are apparently heterogeneous. We report a patient with AIGA in whom the eccrine glands were histologically normal. However, electron microscopic examination showed markedly low numbers of nerve terminals and unmyelinated axons associated with the eccrine glands. Our laboratory investigations suggest that degeneration of postganglionic sympathietic cholinergic nerve may be the underlying pathogenetic mechanism of anhidrosis in this patient.
Correlation between cytomegalovirus infection and IgM anti‐MAG/SGPG antibody–associated neuropathy
Authors: Yuki Nobuhiro , Yamamoto Takako , Hirata Koichi 
Published: January 2005

AbstractIgM anti–myelin‐associated glycoprotein (anti‐MAG)/sulfated glucuronyl paragloboside (SGPG) antibody is found in some patients with chronic polyneuropathy (CP). An antigen‐driven process is considered to induce this autoantibody, but the agent has yet to be identified. It has been reported that sera from cytomegalofvirus (CMV)‐infected patients contained anti‐SGPG antibody. To clarify the mechanism of the production of the anti‐MAG/SGPG antibody, we investigated CMV DNA in sera from 26 patients with IgM anti‐MAG/SGPG antibody–positive CP. Twenty‐three (88%) had CMV DNA. The positive frequency was significantly higher than the freqencies in sera from patients with IgM anti‐MAG/SGPG–negative CP, the other disease controls, and the normal control subjects. There were no statistical differences in the frequencies of Epstein‐Barr virus DNA between anti‐MAG/SGPG–positive and anti‐MAG/SGPG–negative CP and between anti‐MAG/SGPG–positive CP and each disease control. Moreover, no herpes simplex virus 1 DNA was detected in the sera from patients with anti‐MAG/SGPG–positive CP. The strong correlation of anti‐MAG/SGPG–positive CP with the presence of serum CMV DNA suggests that CMV infection induces the IgM anti‐MAG/SGPG antibody.
Antibodies against Helicobacter pylori were detected in the cerebrospinal fluid obtained from patients with guillain‐barré syndrome
Authors: Chiba Susumu , Sugiyama Toshiro , Matsumoto Hiroyuki , Hisano Kazunari , Awakawa Teruhito , Hiura Kazumi , Saitoh Masaki , Imai Kohzoh 
Published: January 2005

AbstractWe examined the antibodies against Helicobacter pylori proteins in the cerebrospinal fluid (CSF) of 7 patients with Guillain‐Barré syndrome (GBS). Crude H. pylori antigens, fractionated heat shock protein (HSP), and urease B (UB) from H. pylori antigens were separated by SDS‐PAGE. With Western blot analysis, four of seven CSF samples had several IgG antibodies against H. pylori proteins, including HSP and UB. No cross reactivity against Campylobacter jejuni was observed. These antibodies may be involved in the immune responses of patients with GBS.
D2 receptor binding in dopa‐responsive dystonia
Authors: Künig Gabriella , Leenders Klaus L. , Antonini Angelo , Vontobel Peter , Weindl Adolf , Meinck Hans M. 
Published: January 2005

AbstractWe have studied dopamine D2 receptor binding by [11C]raclopride positron emission tomography in 14 patients with dopa‐responsive dystonia (DRD). Data were compared with 16 levodopa‐treated patients with Parkinson's disease (PD) and 26 healthy controls. The results revealed an elevated [11C]raclopride binding index in the putamen and caudate nucleus of DRD patients compared with controls as well as significant elevation in the caudate nucleus compared with PD patients. The increase of [11C]raclopride binding may be interpreted either as reduced tracer displacement by endogenous dopamine, or as an alteration of the receptor features due to chronic dopamine deficiency. The difference in [11C]raclopride binding in DRD and PD patients in the caudate nucleus suggests that this structure may be of pathophysiological relevance in the presentation of the clinical features of both diseases.
Adult polyglucosan body disease in Ashkenazi Jewish patients carrying the Tyr329 Ser mutation in the glycogen‐branching enzyme gene
Authors: Lossos Alexander , Meiner Zeev , Barash Varda , Soffer Dov , Schlesinger Ilana , Abramsky Oded , Argov Zohar , Shpitzen Shoshi , Meiner Vardiella 
Published: January 2005

AbstractAdult polyglucosan body disease (APBD) is a late‐onset, slowly progressive disorder of the nervous system caused by glycogen branching enzyme (GBE) deficiency in a subgroup of patients of Ashkenazi Jewish origin. Similar biochemical finding is shared by glycogen storage disease type IV (GSD IV) that, in contrast to APBD, is an early childhood disorder with primarily systemic manifestations. Recently, the GBE cDNA was cloned and several mutations were characterized in different clinical forms of GSD IV. To examine whether mutatins in the GBE gene account for APBD, we studied 7 patients from five Jewish families of Ashkenazi ancestry. The diagnosis was based on the typical clinical and pathological findings, and supported by reduced GBE activity. We found that the clinical and biochemical APBD phenotype in all five families cosegregated with the Tyr329Ser mutation, not detected in 140 controls. As this mutation was previously identified in a nonprogressive form of GSD IV and was shown in expression studies to result in a significant residual GBE activity, present findings explain the late onset and slowly progressive course of APBD in our patients. We conclude that APBD represents an allelic variant of GSD IV, but the reason for the difference in primary tissue involvement must be established.
Neuromuscular blockade by IgG antibodies from patients with Guillain‐Barré syndrome: A macro‐patch‐clamp study
Authors: Buchwald Brigitte , Toyka Klaus V. , Zielasek Jürgen , Weishaupt Andreas , Schweiger Susanna , Dudel Josef 
Published: January 2005

AbstractGuillain‐Barré syndrome (GBS) is often associated with serum antibodies to glycoconjugates such as GM1 and GQ1b. The pathogenic role of these antibodies and other serum factors has not yet been clarified. We have investigated the effect of serum, plasma filtrate, and highly purified IgG and IgM from 10 patients with typical GBS on motor nerve terminals in the mouse hemidiaphragm. Quantal endplate currents were recorded by means of a perfused macro‐patch‐clamp electrode. The plasma filtrate of all GBS patients led to a 5‐ to 20‐fold reduction of evoked quantal release within 7 to 15 minutes of continuous superfusion. In 4 patients, the amplitudes of single quanta were clearly reduced (by 10–66% of control values), indicating an additional postsynaptic action. Blocking effects could be reversed to a variable degree within 15 to 18 minutes after washout. Purified IgG was as effective as native serum, whereas a purified GBS IgM fraction did not block transmission. Sera from convalescent patients and IgM from healthy subjects were without blocking effect. The effects were complement independent and there was no link to the presence (in 6 patients) or absence (in 4 patients) of detectable antibodies to GM1 or GQ1b. In GBS, antibodies to an undetermined antigen depress the presynaptic transmitter release and, in some cases, the activation of postsynaptic channels. We suggest that weakness in the acute stage of GBS may be caused in part by circulating antibodies.
The change in volume of the olfactory and accessory olfactory bulbs of the albino rat during postnatal life
Authors: Smith C. G. 
Published: January 2005

AbstractTransverse sections of the olfactory bulbs were prepared for seventy‐one male and six female albino rats, all of which were of the Experimental Colony strain obtained from The Wiostar Institute. These were selected and grouped according to age so that representative ages throughout the whole of the postnatal life cycle are available.
The cochlear nuclei in the common porpoise, Phocaena phocaena
Authors: Osen Kirsten Kjelsberg , Jansen Jan 
Published: January 2005

AbstractThe structure of the primary cochlear nuclei in three specimens of the common porpoise, Phocaena phocaena, has been studied in transverse and sagittal sections stained for cells (Nissl) and myelin sheaths. A rudimental dorsal cochlear nucleus and a very large ventral cochlear nucleus were found. The large cochlear nerve (nine tenths of the entire VIII nerve) enters the rostral pole of the ventral cochlear nucleus within which it fans out to form ascending and descending fibers. Five subdivisions were distinguished in the ventral nucleus, viz., the anterior part, the posterior part, the dorsolateral part, the dorsomedial part, and the interstitial part.Great similarity exists between the Phocaena and other toothed whales with regard to the structure of the cochlear nuclei. Neither seems any principal difference to exist in this respect between the Phocaena and the landliving mammals, especially when compared with the primates which have likewise a poorly differentiated dorsal nucleus. The five subdivisions of the ventral nucleus of Phocaena presumably are the homologues of the subdivisions distinguished by Fuse ('13) and Lorente de Nó ('33) in the corresponding nucleus of terrestrial mammals. The enormous size of the ventral cochlear nucleus is the only reliable criterion observed that might reasonably be associated with the extraordinary sense of hearing in Cetacea.