bluuebunny/crossref_metadata_2025 huggingface dataset:
(R) salsolinol N‐methyltransferase activity increases in parkinsonian lymphocytes
Authors: Naoi Makoto , Maruyama Wakako , Nakao Naoki , Ibi Tohru , Sahashi Ko , Benedetti Margherita Strolin
Published: January 2005

Recently, an endogenous catechol isoquinoline, 1(R),2(N)‐;6,7‐dihydroxy‐1,2,3,4‐tetrahydroisoquinoline [N‐methyl(R)salsolinol], was proved to be a neurotoxin specific for dopamine neurons by in vivo and in vitro experiments. This N‐methyl(R)salsolinol was found to increase significantly in the cerebrospinal fluid of untreated parkinsonian patients, suggesting its possible involvement in the pathogenesis of Parkinson's disease. To clarify the mechanism of the increase, the activity of enzymes related to the metabolism of the neurotoxin was examined in lymphocytes prepared from parkinsonian patients and controls. In patients with Parkinson's disease, the activity of a neutral N‐methyltransferase, measured by using (R)salsolinol as a substrate, was found to increase significantly (100.2 ± 81.8 pmol/min/mg of protein) in comparison with that in controls (18.9 ± 15.0 pmol/min/mg of protein). The distribution of the activity was bimodal in the parkinsonian patients, whereas it was singular in controls. The activity of other related enzymes, an alkaline N‐methyltransferase and N‐methyl(R)salsolinol oxidase, in parkinsonian lymphocytes was the same as in controls. Increase of the neutral N‐methyltransferase may be an endogenous factor in the pathogenesis of Parkinson's disease.
Increased Aβ42(43) from cell lines expressing presenilin 1 mutations
Authors: Mehta Nitin D. , Refolo Lawrence M. , Eckman Chris , Sanders Sunny , Yager Debra , Perez‐Tur Jordi , Younkin Steve , Duff Karen , Hardy John , Hutton Mike
Published: January 2005

Mutations in the presenilin 1 (PS1) gene on chromosome 14 are a major cause of autosomal dominant, early‐onset Alzheimer's disease. Here, we show that transfecting cells with several mutant, but not wild‐type, PS1 cDNAs alters the processing of the amyloid precursor protein (APP) such that more Aβ42(43) is produced, confirming and extending several recent reports. The most effective mutation in this regard was the exon 9 splice‐out mutation (δ9). The correlation between the size of the effect on APP processing and the age of onset of disease assessed in families with the mutations was not informative, and the possible reasons for this are discussed.
Eye movement abnormalities correlate with genotype in autosomal dominant cerebellar ataxia type I
Authors: Rivaud‐Pechoux Sophie , Dürr Alexandra , Gaymard Bertrand , Cancel Géaraldine , Ploner Christoph J. , Agid Yves , Brice Alexis , Pierrot‐Deseilligny Charles
Published: January 2005

We compared horizontal eye movements (visually guided saccades, antisaccades, and smooth pursuit) in control subjects (n = 14) and patients with three forms of autosomal dominant cerebellar ataxias type I: spinocerebellar ataxias 1 and 2 (SCA1, n = 11; SCA2, n = 10) and SCA3/Machado‐Joseph disease (MJD) (n = 16). In SCA1, saccade amplitude was significantly increased, resulting in hypermetria. The smooth pursuit gain was decreased. In SCA2, saccade velocity was markedly decreased. The percentage of errors in antisaccades was greatly increased and was significantly correlated with age at disease onset. In addition, a correlation between smooth pursuit gain and the number of trinucleotide repeats was found. In SCA3, gaze‐evoked nystagmus was often present as was saccade hypometria and smooth pursuit gain was markedly decreased. Three major criteria, saccade amplitude, saccade velocity, and presence of gaze‐evoked nystagmus, permitted the correct assignment of 90% of the SCA1, 90% of the SCA2, and 93% of the patients with SCA3 to their genetically confirmed patient group and, therefore, may help orient diagnose of SCA1, SCA2, and SCA3 at early clinical stages of the diseases.
Molecular mapping of alzheimer‐type dementia in Down's syndrome
Authors: Prasher V. P. , Farrer Matthew J. , Kessling Anna M. , Fisher Elizabeth M. C. , West R. J. , Barber P. C. , Butler A. C.
Published: January 2005

Previous research has hypothesized an association between Alzheimer's disease and the amyloid precursor protein (APP) gene found on chromosome 21. We report the case of a 78‐year‐old woman with Down's syndrome with partial trisomy 21 [46,XX,rec(21)dup q, inv(21) (p12q22.1)]. No evidence of Alzheimer's disease was found on neuropsychological, magnetic resonance imaging, and neuropathological assessment. The gene sequence for APP was present in only two copies. This case further supports the hypothesis that Alzheimer's disease is associated with trisomy for proximal chromosome 21q, including the APP gene.
In vivo PET Imaging in rat of dopamine terminals reveals functional neural transplants
Authors: Brownell Anna‐Liisa , Livni Eli , Galpern Wendy , Isacson Ole
Published: January 2005

Positron emission tomography (PET) and carbon‐11‐labeled 2B‐carbomethoxy‐3B‐(4‐fluorophenyl)tropane (11C‐CFT or 11‐WIN 35,428) were used as molecular markers for striatal presynaptic dopamine (DA) transporters in a unilateral Parkinson's disease rat neurotransplantation model. In the lesioned striatum, the binding ratio measured by the DA presynaptic marker was reduced to 15% to 35% of the intact side (or unoperated control). After grafting with non‐DA cells (from dorsal mesencephalon), the DA binding ratio remained reduced to levels observed before transplantation and rats showed no behavioral recovery. In contrast, after DA neuronal transplantation, behavioral recovery occurred only after the 11C‐CFT binding ratio had increased to 75% to 85% of the intact side. This study provides direct in vivo evidence for the dopaminergic molecular basis of functional recovery in the lesioned nigrostriatal system after neural transplantation.
Primary position upbeat nystagmus due to unilateral medial medullary infarction
Authors: Hirose Genjiro , Ogasawara Tomoko , Shirakawa Tomoyasu , Kawada Jyunya , Kataoka Satoshi , Yoshioka Akira , Halmagyi G. Michael
Published: January 2005

We report on a patient who developed primary position upbeat nystagmus (ppUBN) due to a unilateral medial medullary infarction. On oculography, the slow phases of the nystagmus sometimes had an exponentially decreasing velocity waveform, indicating that the nystagmus was due to impairment of the vertical position‐to‐velocity neural integrator. On magnetic resonance imaging, the lesion was caudal to the vestibular nuclei and to the most rostral of the perihypoglossal nuclei, the nucleus intercalatus, a structure that was also involved in a previously reported case of ppUBN due to a unilateral medullary lesion. On the basis of these imaging and oculographic observations, we propose that a unilateral lesion of the nucleus intercalatus is sufficient to cause ppUBN and that the nucleus intercalatus is a part of the vertical position‐to‐velocity neural integrator in the human ocular–motor system.
Purified IgG from seropositive and seronegative patients with myasthenia gravis reversibly blocks currents through nicotinic acetylcholine receptor channels
Authors: Bufler Johannes , Pitz Roland , Czep Micheal , Wick Manfred , Franke Christian
Published: January 2005

The mechanism of block of nicotinic acetylcholine receptor (nAChR) channels by purified antibodies from patients with myasthenia gravis (MG) was investigated by using an ultrafast system for solution exchange at outside‐out patches. IgG of MG patients and controls was purified by using protein A–Sepharose columns. Probes from 9 seropositive MG patients and 3 seronegative MG patients were tested. As a preparation, cultured mouse myotubes expressing the embryonic‐type nAChR channels were used. Twenty‐millisecond pulses of 1.0 mM ACh were applied repetitively to outside‐out patches. Outside‐out patches were preexposed with IgG in concentrations between 0.1 and 200 mg/L during application of ACh pulses. The peak current amplitude was reduced to values between 6% and 71% of control for the 9 seropositive and 3 seronegative MG patients. The block was concentration dependent and fully reversible after washout of antibodies. Incubation with IgG from different control patients did not reduce the peak current amplitude. In addition, our findings with purified IgG from seronegative MG patients support the idea of the immunopathogenesis of this disorder and may allow the development of a diagnostic test for seronegative MG patients.
The role of type III collagen in spontaneous cervical arterial dissections
Authors: van Den Berg J. S. P. , Limburg M. , Kappelle L. J. , Pals G. , Arwert F. , Westerveld A.
Published: January 2005

A case‐control study was carried out to investigate whether type III collagen deficiency plays a role in the pathogenesis of spontaneous cervical arterial dissections. In 16 patients with spontaneous cervical arterial dissections and in 41 healthy controls, protein analysis of type III collagen (ratio of type III/type I collagen) was performed. Futhermore, single‐stranded conformation polymorphism/heteroduplex analysis was used to investigate the type III collagen gene in the 16 patients with spontaneous cervical dissections to detect mutations. The ratios of type III/type I collagen in the controls ranged from 5.5 to 19.8% (median, 10%). The ratios of type III/type I collagen in the patients with spontaneous cervical arterial dissections ranged from 3.2 to 17.9% (median, 9.3%). Two patients had a low ratio of type III/type I collagen (<5.5%). No abnormalities suggesting a mutation in the gene of type III collagen were demonstrated in any of the 16 patients. Our findings are in keeping with the hypothesis that a reduced production of type III collagen may contribute to the formation of spontaneous cervical arterial dissections in some patients. The absence of a responsible mutation indicates that the coding sequence of the type III collagen gene is not involved.
Absence of transcallosal inhibition following focal mangnetic stimulation in preschool children
Authors: Heinen Florian , Glocker Franz‐Xaver , Fietzek Urban , Meyer Bernd‐Ulrich , Lücking Carl‐Hermann , Korinthenberg Rudolf
Published: January 2005

Focal transcranial magnetic stimulation of the hand‐associated motor cortex was used to study normal healthy preschool children (n = 7; mean age, 4.6 years) and adults (n = 7; mean age, 29.4 years) under the conditions of standardized tonic voluntary contraction of small hand muscles. Callosally mediated inhibitory as well as corticospinally mediated inhibitory and excitatory motor effects were investigated. Although children had no detectable transcallosal inhibition, their corticospinally mediated postexcitatory silent period was present (mean, 140.8 ± 30.2 msec). It was significantly shorter then in adults (mean, 192.5 ± 32.0 msec). The motor thresholds of the cortically elicited muscle responses, measured as the lowest stimulus intensity, were significantly higher in children (mean, 89 ± 5%) than in adults (mean, 46 ± 6%). The corticomuscular latency of transcranially elicited motor responses revealed no difference between children and adults. These observations may reflect maturation processes in the motor system. Maturation of at least some direct corticospinal fibers occurs early in life and is followed by that of intracortical excitatory and inhibitory connections. The maturation of functionally competent callosal connections appears to occur after the age of 5 years.
Cyclooxygenase‐2 is induced globally in infarcted human brain
Authors: Sairanen Tiina , Ristimäki Ari , Karjalainen‐Lindsberg Marja‐Liisa , Paetau Anders , Kaste Markku , Lindsberg Perttu J.
Published: January 2005

Cyclooxygenase (COX) catalyzes synthesis of prostanoids after liberation of arachidonic acid, an important biochemical sequela of cerebral ischemia that aggravates brain injury. We investigated expression of inducible COX‐2 in infarcted human brains (symptom duration, 15 hours to 18 days) and found that COX‐2 protein was present in both neuronal and glial cells throughout the brain in accord with infarct topography and duration. These results emphasize the global yet temporally regulated nature of COX‐2 induction during focal ischemia in humans, clearly different from the circumscribed acute expression reported in experimental animal models. We speculate that early induction of COX‐2 may fuel tissue damage through prostanoids and free radicals, and delayed induction in remote brain areas may promote reconstitutive processes in the face of tissue scarring and remodeling of the surviving neural networks.
Descriptive epidemiology of Creutzfeldt‐Jakob disease in six european countries, 1993–1995
Authors: Will R. G. , Alperovitch A. , Poser S. , Pocchiari M. , Hofman A. , Mitrova E. , de Silva R. , D'Alessandro M. , Delasnerie‐Laupretre N. , Zerr I. , van Duijn C. ,   EU collaborative Study Group for CJD
Published: January 2005

After the occurrence of bovine spongiform encephalopathy (BSE), there has been concern that transmission of BSE to the human population might result in a change in the epidemiological characteristics of Creutzfeldt‐Jakob disease (CJD). A collaborative study of CJD in the European Union was performed from 1993 to 1995, to compare data from national registries for CJD in France, Germany, Italy, The Netherlands, Slovakia, and the United Kingdom. Five hundred seventyfive patients with definite or probable CJD died in the study period with an overall annual morality rate of 0.71 cases per million. The incidence rates for CJD were similar in all participating countries despite variations in postmortem rates, and age‐specific incidence rates were also relatively consistent, with the exception of an increased incidence of CJD in patients younger than 39 years of age in the United Kingdom. In relation to etiological subtypes of CJD, 87% of cases were sporadic, 8% genetic, and 5% iatrogenic. Genetic forms of CJD comprised 80% of all cases in Slovakia, and iatrogenic forms of CJD occurred most frequently in France and the United Kingdom. The statistical data reported here do not provide evidence of a causal link between BSE and CJD in Europe as a whole. However, the study has established baseline epidemiological parameters for CJD in participating European countries, which may be important in the assessment of any future change in the characteristics of CJD as a result of the epidemic of BSE.
N‐glycolylneuraminic acid–containing GM1 is a new molecule for serum antibody in Guillain‐Barré syndrome
Authors: Odaka Masaaki , Yuki Nobuhiro , Yoshino Hiide , Kasama Takeshi , Handa Shizuo , Irie Fumitoshi , Hirabayashi Yoshio , Suzuki Akemi , Hirata Koichi
Published: January 2005

To clarify the pathogenesis of Guillain‐Barré syndrome (GBS) after parenteral injections of bovine brain gangliosides, we searched for new molecules in bovine brain gangliosides recognized by sera from GBS patients. Gangliosides fractionated in a Q‐Sepharose column were used as the antigens, and the binding of serum IgG or IgM was examined by thin‐layer chromatography/immunostaining. Fourteen of 175 serum samples from the patients reacted with the monosialoganglioside fraction 2. In the neutral solvent system, a band in this fraction migrated with N‐acetylneuraminic acid‐containing GM1 [GM1(NeuAc)], whereas in the alkaline solvent system it migrated slower. This suggested that the band was N‐glycolylneuraminic acid‐containing GM1 [GM1(NeuGc)]. In both solvent systems, its mobility was almost the same as that of authentic GM1(NeuGc) from mouse liver. Secondary ion mass spectrometry showed that the ganglioside's structure was consistent with that of GM1(NeuGc). IgG anti‐GM1(NeuGc) antibodies in sera from the GBS patients were significantly absorbed by GM1(NeuAc), indicative that the anti‐GM1(NeuGc) antibodies cross‐react with GM1(NeuAc). N‐Glycolylneuraminic acid‐containing gangliosides are so highly immunogenic in humans that the injection of GM1(NeuGc) could induce the production of IgG anti‐GM1(NeuGc) antibody, which cross‐reacts with GM1(NeuAc).
Incidence of exacerbations in the first 90 days of treatment with recombinant human interferon β‐1b in patients with relapsing‐remitting multiple sclerosis
Authors: Khan Omar A. , Hebel J. Richard
Published: January 2005

Interferon β‐1b (IFNβ1B) is effective in reducing the frequency of exacerbations in patients with relapsing‐remitting multiple sclerosis (RRMS). Recently, a study suggested that treatment with IFNβ‐1b may place MS patients at risk of exacerbations by increasing interfreon‐β (IFNγ) sereting cells in the blood early after onset of treatment. We conducted a retrospective study in 192 RRMS patients treated with IFNβ‐1b. We did not observe an increase in the frequency of exacerbations early after the onset of treatment and suggest that the IFNγ‐secreting cell surge linked to the onset of treatment with IFNβ‐1b may not be clinically significant.
Autosomal dominant myopathy with congenital joint contractures, ophthalmoplegia, and rimmed vacuoles
Authors: Darin N. , Kyllerman M. , Wahlström J. , Martinsson T. , Oldfors A.
Published: January 2005

We describe a new myopathy in a large family with 19 affected cases. Inheritance was autosomal dominant. Characteristic clinical features were congenital joint contractures, which normalized during early childhood, external ophthalmoplegia, and proximal muscle weakness. Muscle atrophy was most prominent in the pectoralis and quadriceps muscles. The clinical course was nonprogressive in childhood, but most adult cases experienced deterioration of muscle function, starting from 30 to 50 years of age. The major histopathological change of skeletal muscle in childhood was focal disorganization of myofilaments. In adults with progressive muscle weakness, the muscle biopsies showed dystrophic changes and rimmed vacuoles with cytoplasmic and intranuclear inclusions of 15‐ to 21‐nm filaments. These findings suggests that this new disease should be classified as a variant of hereditary inclusion body myopathy.
Time course of corticospinal excitability in reaction time and self‐paced movements
Authors: Chen Robert , Yaseen Zaneb , Cohen Leonardo G. , Hallett Mark
Published: January 2005

We used transcranial magnetic stimulation (TMS) to study the time course of corticospinal excitability before and after brisk thumb abduction movements, either in a simple reaction time (RT) paradigm or self‐paced. Premovement increase in corticospinal excitability began about 20 msec earlier for self‐paced compared with simple RT movements. For both simple RT and self‐paced movements after electromyographic (EMG) offset, there was a first period of increased excitability from 0 to 100 msec, followed by a second period from 100 to 160 msec. Corticospinal excitability was decreased from about 500 to 1,000 msec after EMG offset for both types of movements. Our results show that motor preparation that begins 1.5 to 2 seconds before self‐paced movement is not associated with increased corticospinal excitability. The first phase of increased corticospinal excitability after EMG offset may be due to activity of motor cortex neuron subthreshold for activating spinal motor neurons, and the second phase may reflect a subthreshold second agonist burst. The period of decreased corticospinal excitability after movement corresponds to the onset of event‐related synchronization (ERS) of electroencephalographic signals in the 20‐Hz band, and supports the hypothesis that ERS may be related to an inactive, idling state of the motor cortex.
Predictive factors for prolonged survival in acquired immunodeficiency syndrome—associated progressive multifocal leukoencephalopathy
Authors: Berger Joseph R. , Levy Robert M. , Flomenhoft Deborah , Dobbs Michael
Published: January 2005

Progressive multifocal leukoencephalopathy (PML) complicating the acquired immunodeficiency syndrome (AIDS) is typically inexorably progressive with death usually occurring within 6 months of symptom onset. Occasional patients have been observed to survive longer than 1 year, often with remission of clinical features. In this study, we identify predictive factors for prolonged survival in patients with biopsy proven, AIDS‐associated PML, by comparing 7 patients with survival exceeding 12 months from symptom onset with 45 patients with shorter survivals. PML was the presenting manifestation of AIDS in 5 (71.4%) of 7 long‐term survivors compared with 8 (17.8%) of 45 short‐term survivors. CD4 T‐lymphocyte counts were substantially higher in the long‐term survivors, with 3 (42.9%) of 7 having counts exceeding 300 cells/mm3 in comparison with only 1 (4.3%) of 23 short‐term survivors. Contrast enhancement on radiographic imaging was observed in 3 (50%) of 6 long‐term survivors in comparison with 4 (8.9%) of 45 short‐term survivors. Neurological recovery and radiographic improvement were not observed in any short‐term survivors but were seen in 5 (71.4%) long‐term survivors. There was no association between treatment modalities and survival. Predictors of long‐term survival in AIDS patients with PML include PML as the heralding manifestation of AIDS, high CD4 T‐lymphocyte count at disease onset, lesion enhacement on computed tomographic scan or magnetic resonance imaging, and evidence of recovery of neurological function.
Acute inflammatory demyelinating polyradiculopathy in children: Clinical and electrodiagnostic studies
Authors: Delanoe Catherine , Sebire Guillaume , Landrieu Pierre , Huault Gilbert , Metral Stéphane
Published: January 2005

Clinical and electrophysiological features in 43 children with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) were retrospectively studied. More than one‐third of these children were less than 3 years old. Some distinctive clinical features specific to adults or to children were identified. Initial symptoms such as ataxia and severe limb or back pain were more frequent in children. By using the criteria suggested here, according to our neurophysiological findings, the diagnosis of AIDP could be proposed as early of the first days of illness in 90% of the children and is confirmed during the second week. The neurophysiological evolution was very similar in children and adults except that recovery occurred sooner in children. Prognosis was better in childhood (complete recovery in all but 2 patients with minor disabilities).
Dominant negative effect of GTP cyclohydrolase I mutations in dopa‐responsive hereditary progressive dystonia
Authors: Hirano Makito , Yanagihara Takehiko , Ueno Satoshi
Published: January 2005

Herediatary progressive dystonia (HPD) is caused by the mutant gene encoding GTP cyclohydrolase I (GCH). The clinical presentation of this disease varies considerably, and many cases appear to be sporadic. We have previously proposed that this clinical variation may be due to differential expression of the mutant and normal GCH mRNA, presumably at the protein level. To provide support for this proposal, we studied a new Japanese family with HPD, in which 2 members were heterozygous for an exon‐skipping mutation. This mutation produced truncated GCH, which shared 180‐amino acid residues at the amino terminus of the normal enzyme (GCH180). An affected heterozygote had a higher mutant/normal mRNA ratio than an unaffected heterozygote, consistent with our previous finding in the HPD family with GCH114. A further study, using coexpression of the mutant with wild‐type GCH in COS‐7 cells, showed that three mutant GCHs inactivated the normal enzyme. GCH114 was most effective in enzyme inactivation, which was followed by GCH180 and a normally occurring mutant GCH209. These results suggested that the dominant negative effect of a mutant GCH on the normal enzyme might be one of the molecular mechanisms determining the heterogeneity of clinical phenotypes of HPD.
Somatotopical organization of striatal activation during finger and toe movement: A 3‐T functional magnetic resonance imaging study
Authors: Lehéricy Stéphane , van de Moortele Pierre‐François , Lobel Elie , Paradis Anne‐Lise , Vidailhet Marie , Frouin Vincent , Neveu Pascal , Agid Yves , Marsault Claude , Le Bihan Denis
Published: January 2005

The present study aimed at determining the distribution and somatotopical organization of striatal activation during performance of simple motor tasks. Ten right‐handed healthy volunteers were studied by using a 3‐T whole‐body magnetic resonance unit and echo planar imaging. The tasks consisted of self‐paced flexion/extension of the right fingers or toes. Motor activation was found mainly in the putamen posterior to the anterior commissure (10 of 10 subjects) and the globus pallidus (6 subjects), whereas the caudate nucleus was activated in only 3 subjects, and in a smaller area. Thus, performance of a simple motor task activated the sensorimotor territory of the basal ganglia. Within the putamen, there was a somatotopical organization of the foot and hand areas similar to that observed in nonhuman primates. These data suggest that functional magnetic resonance imaging can be used to study normal function of the basal ganglia and should therefore also allow investigation of patients with movement disorders.
A subgroup of multiple sclerosis patients with anticardiolipin antibodies and unusual clinical manifestations: Do they represent a new nosological entity?
Authors: Karussis Dimitrios , Leker Ronen R. , Ashekenazi Avi , Abramsky Oded
Published: January 2005

The presence of antibodies to cardiolipin (ACL Abs) has been reported in some patients suffering from multiple sclerosis (MS), especially of the “neuromyelitic” type. In addition, bright T2‐imaging foci (unidentified bright objects) are occasionally detected on brain magnetic resonance imaging (MRI) scans, in patients with antiphospholipid syndrome. From a cohort of 100 patients with a probable or definite diagnosis of MS according to Poser's criteria, we isolated a subgroup of 20 patients (8 males and 12 females) consistently positive for ACL Abs. These patients were followed up neurologically for 1 to 3 years and brain MRI scanning and a complete autoimmune screening were performed. Nineteen (19 of 20) of our patients had the classic neuroimaging features of MS (multiple white‐matter T2 bright foci on the MRI scan). The most common neurological syndrome was chronic, slowly progressing myelopathy (presenting as myelopathy, neuromyelitis optica, or spinocerebellar syndrome; 15 of 20), and optic neuropathy (6 of 20). Headache was a dominant symptom in 8 of 20 patients. Less common symptoms included cognitive and psychiatric disorders and chronic fatigue. The mean levels of ACL Abs were 38.8 ± 28.2 GPL (normal values up to 7.5). Oligoclonal bands in the cerebrospinal fluid were detected in only 3 of 20 patients. Patients were treated with acetylsalycilic acid and occasionally with short courses of steroids. The progression of the chronic myelopathic/spinocerebellar syndrome was slower than expected in MS (only 2 patients deteriorated whereas 4 improved during a mean follow‐up period of 20.8 ± 7.1 months). We conclude that patients with probable or definite diagnosis of MS, and consistently elevated levels of ACL Abs show a slower progression and some atypical (for MS) features, such as persistent headaches and absence of oligoclonal bands in the cerebrospinal fluid. In these patients, other, presumably vascular, mechanisms may be involved in the pathogenesis of the neurological symptoms. Therefore, management should include antiplatelet or even anticoagulant agents.
Presence of 4‐hydroxynonenal in cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis
Authors: Smith R. Glenn , Henry Y. Kay , Mattson Mark P. , Appel Stanley H.
Published: January 2005

A marker of lipid peroxidation 4‐hydroxynonenal (HNE) was elevated in the cerebrospinal fluid (CSF) of a patient with sporadic amyotrophic lateral sclerosis (sALS) compared with that of most patients with other neurological diseases. Such elevations of HNE were sufficient to kill cyclic adenosine monophosphate (cAMP)‐differentiated motor neuron hybrid cells in vitro, and anti‐oxidants prevented this HNE‐dependent cell death. These data suggest that oxidative stress and lipid peroxidation are associated with and may promote motor neuron degeneration in sALS.
Clinical approach to inherited peroxisomal disorders: A series of 27 patients
Authors: Baumgartner M. R. , Poll‐The B. T. , Verhoeven N. M. , Jakobs C. , Espeel M. , Roels F. , Rabier D. , Levade T. , Rolland M. O. , Martinez M. , Wanders R. J. A. , Saudubray J. M.
Published: January 2005

To illustrate the clinical and biochemical heterogeneity of peroxisomal disorders, we report our experience with 27 patients seen personally between 1982 and 1997. Twenty patients presented with a phenotype corresponding either to Zellweger syndrome, neonatal adrenoleukodystrophy, or infantile Refsum disease, 3 of whom had a peroxisomal disorder due to a single enzyme defect. One patient had a mild form of rhizomelic chondrodysplasia punctata, 1 had classic Refsum disease. Finally, 5 patients presented with clinical manifestations that were either unusually mild or completely atypical, and initially did not arouse suspicion of a peroxisomal disorder. They showed multiple defects of peroxisomal functions with one or several functions remaining intact, suggesting a peroxisome biogenesis disorder. The defect in peroxisome biogenesis was further characterized by variable expression in different tissues and/or individual cells in 5 patients. Studies restricted to fibroblasts failed to identify abnormalities in this group. We demonstrate that clinical manifestations of peroxisomal disorders may be very mild or completely atypical, and therefore, peroxisomal disorders should be considered in a variety of clinical settings. Furthermore, we suggest performing extensive peroxisomal investigations in every patient suspected of suffering from a peroxisomal disorder, even when the clinical presentation is typical.
Genetic contribution of the tumor necrosis factor region in guillain‐barré syndrome
Authors: Ma J. J. , Nishimura M. , Mine H. , Kuroki S. , Nukina M. , Ohta M. , Saji H. , Obayashi H. , Kawakami H. , Saida T. , Uchiyama T.
Published: January 2005

We studied genetic polymorphisms in the tumor necrosis factor (TNF) region in 81 Japanese patients with Guillain‐Barré syndrome (GBS) and 85 controls. A significantly higher frequency of the 100–base pair (bp) (TNFa2) allele of the TNFa microsatellite marker, which is associated with high TNFα production, existed in Campylobacter jejuni‐positive (Cj+) GBS patients than in controls, suggesting the involvement of a genetic predisposition to high TNFα secretion in the development of c. jejuni‐related GBS.
Seasonal variation of interferon‐γ production in progressive multiple sclerosis
Authors: Balashov Konstantin E. , Olek Michael J. , Smith Derek R. , Khoury Samia J. , Weiner Howard L.
Published: January 2005

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. There is increased interferon (IFN)‐γ secretion in MS patients in vitro, and IFN‐γ administration induces exacerbations of disease suggesting a link between IFN‐γ and disease activity. We observed significantly increased IFN‐γ production in the autumn and winter months compared with the spring and summer months in chronic progressive MS, and this increase was linked to endogenous interleukin (IL)‐12 production. Increased seasonal IFN‐γ was not observed in normal control subjects, and there were no seasonal changes in IL‐10 in progressive MS. These results suggest a potential environmental link between dysregulated IFN‐γ production and MS disease progression and pathogenesis.
The Glu318Gly mutation of the presenilin‐1 gene does not necessarily cause Alzheimer's disease
Authors: Mattila Kari M. , Forsell Charlotte , Pirttila Tuula , Rinne Juha O. , Lehtimaki Terho , Roytta Matias , Lilius Lena , Eerola Anne , George‐Hyslop Peter H. St , Frey Harry , Lannfelt Lars
Published: January 2005

In early‐onset familial Alzheimer's disease pathogenic mutations have been found in the amyloid precur sor protein (APP) gene and in the presenilin (PS)‐1 and PS‐2 genes. We screened for mutations in these genes in 20 patients with familial AD from the Finnish population. In addition, we sampled 41 sporadic AD patients and 59 controls to test for mutations identified in our familial AD cases. We detected an A‐to‐G transition in the PS‐1 gene, resulting in a glutamic acid (G1u)‐to‐ glycine (Gly) substitution at codon 318 in 2 familial and 2 sporadic AD patients. The Glu318Gly mutation has previously been reported to cause AD. We also found the Glu318Gly mutation in 4 healthy aged controls (range, 74–87 years). We thus conclude that the mutation is most likely a rare polymorphism not related to AD.
Muscle fiber immaturity and inactivity reduce myonecrosis in duchenne muscular dystrophy
Authors: Kimura Shigemi , Sugino Shigeto , Ohtani Yoshinobu , Matsukura Makoto , Nishino Ichizo , Ikezawa Makoto , Sakata Ayako , Kondo Yuichi , Yoshioka Kowashi , Huard Johnny , Nonaka Ikuya , Miike Teruhisa
Published: January 2005

We report on the first case of X‐linked recessive myotubular myopathy (MTM1) coinciding with Duchenne muscular dystrophy (DMD). The muscle biopsy specimens of the patient show only the characteristic findings of MTM1, without the findings of DMD. We theorize that this was caused by the muscle fiber immaturity and inactivity.
The endocranial blood vessels of Amblystoma tigrinum
Authors: Roofe Paul Gibbons
Published: January 2005

The arterial blood supply of the brain of Amblystoma is essentially similar to that of other urodeles so far as these have been described and is comparable in most respects with that of Anura. Individual variations in the courses of even the major arteries are surprisingly great, and the courses of the veins are even more erratic.
The mode of termination and temporal course of degeneration of cortical association pathways in the cerebellum of the cat
Authors: Eager Robert P.
Published: January 2005

The Nauta‐Laidlaw silver degeneration technique was used to study the mode of termination and temporal course of degeneration of cerebellar cortical association pathways in the cat. All associational pathways examined appeared to terminate identically in their respective folia of termination. Two specific cerebellar cortical areas were chosen for detailed discussion and illustration. In the vermis lobules (V and VI), fibers pass from one folium to the adjacent caudal two or three folia, and these pathways can be studied conveniently in the sagittal plane. Long connections extend from anterior lobe paravermal cortex (lobule V) to caudal hemispheral folia of the same side, and these terminations could be examined at a site some distance from the lesion.

Projections of associational pathways displayed a rather strict localization, with terminal areas corresponding in size and location to the area of damaged cortex giving rise to the pathway.

Terminal degeneration was found distributed at Purkinje cell levels and in basal portions of the molecular layer. Some of the degenerated fibers in the molecular layer showed relationships with Purkinje cell dendrites, suggesting that they might be climbing fibers.

Early degenerative changes occurred at two days postoperatively. Maximal fine fiber degeneration occurred at eight days. Fragments of large degenerated fibers were stainable in terminal areas and in folial white matter for as long as 41 days postoperatively.
“Descending” neuronal units in the commissure of the crayfish central nervous system; and their integration of visual, tactile and proprioceptive stimuli
Authors: Wiersma C. A. G. , Mill P. J.
Published: January 2005

The integrative properties of “descending” neuronal units in respect to visual, tactile and proprioceptive stimuli were studied at the commissure level of the crayfish central nervous system and 41 entities were established, bringing the total number of established descending entities at this level to 69. All but three of these are interneurons, over half of which have an entirely homolateral input. Altogether 227 interneurons have so far been established in the crayfish central nervous system, 73 of which extend through more than one of the studied levels. Compared to the thoracic‐abdominal level, interneurons transmitting both anteriorly and posteriorly are very scarce. The properties of high order interneurons are discussed. In addition to those which respond to visual stimuli, or are multimodal, a number react only to mechanorecptive stimulation, and some of this latter type have peripheral sensory fields exclusively posterior to the recording level. A few interneurons, both visual and non‐visual, exibit inhibitory phenomena of various kinds, again mirroring the findings in the mammalian central nervous system. Visual interneurons were shown to respond to specific types of optic stimulation such as movement of objects or changes in light intensity in correspondence with units found in the optic nerves of other decapod crustaceans.
The function of the tectum for attention to auditory stimuli in the cat
Authors: Jane John A. , Masterton R. Bruce , Diamond Irving T.
Published: January 2005

Cats were trained to avoid a shock by moving from one to the other compartment of a double grill box at the onset of a compound signal which consisted of a soft low tone and a bright flashing light. After training on the compound signal unreinforced test trials were given on the tone alone and the light alone. By this procedure the relative potency of sound and light was established for normal cats and cats deprived of various structures in their auditory system. On the basis of this and other subsidiary experiments also reported here, several conclusions seem warranted:

1. In normal cats sound is a prepotent stimulus over light. 2. The prepotency of sound does not depend on the intensities of the competing stimuli. 3. Even with approximately 90% of the second order auditory fibers destroyed, sound is still prepotent over light. 4. Bilateral removal of auditory cortex does not affect the prepotency of sound. 5. Deep bilateral section of the brachia of the inferior colliculus and small bilateral lesions in the apices of the inferior colliculi abolish the prepotency of sound. 6. The loss of the prepotency of sound after midbrain lesions is not the result of a change in absolute threshold for the sound.
The isodendritic core of the brain stem
Authors: Ramón‐Moliner E. , Nauta W. J. H.
Published: January 2005

According to their degree of morphological specialization, the cell populations of the brain stem may be classified into three groups: isodendritic, allodendritic and idiodendritic. The isodendritic neurons, or generalized neurons, are the most frequently encountered. If one discards those isodendritic centers that by common definition are sensory or motor, an isodendritic core is left which displays very little histological variation throughout the whole extent of the brain stem. This core corresponds, with certain restrictions, to the regions that are usually regarded as reticular formation. It constitutes a continuum of overlapping dendritic fields that extends from the spinal cord to the diencephalon. In view of the similarities that exist between the histology of the isodendritic core and the relatively disorganized nervous system of the lower vertebrates, it is postulated that it represents a pool of pluripotential neurons which in the course of phylogeny have remained relatively undifferentiated and in charge of processing afferent signals of very heterogeneous origin. By contrast, the allodendritic and idiodendritic centers can be regarded as relatively specialized centers from the point of view of their dendritic morphology, connections and functions. Attention is paid to the fact that the diffuse characteristics of the isodendritic core do not necessarily entail ill‐defined physiological properties.
Growth alteration in the auditory cortex of visually deprived mice
Authors: Gyllensten Lars , Malmfors Torbjörn , Norrlin Marie‐Louise
Published: January 2005

The diameter of cell nuclei and mean volume of internuclear material per nucleus were determined in the auditory cortex in growing and adult mice. The influence of stay in complete darkness for 2–4 months was investigated.

In growing mice, a decrease in nuclear size and relative volume of internuclear material was observed after two months in the dark from birth. Prolonged stay in the dark caused an increase in nuclear size and internuclear material, and the hypotrophy of the auditory cortex was succeeded by hypertrophy after four months in the dark from birth. In adult mice, reared in darkness for three months from four to seven months of age, similar hypertrophy of the auditory cortex was recorded.

Compared to the findings in the striate cortex of visually deprived mice (in a previous investigation), the initial hypotrophy of the auditory cortex after visual deprivation was less pronounced than the hypotrophy of the auditory cortex after visual cortex. In the latter, no late hypertrophy occurred after prolonged stay in the dark, and hypotrophy was found in the adult, visually deprived mice, and not hypertrophy as in the auditory cortex. The possibility of compensatory auditory training and cortical hypertrophy is discussed.
Behavior of neuro‐epithelial cells during closure of the neural tube
Authors: Langman Jan , Guerrant Richard L. , Freeman Bruce G.
Published: January 2005

Chick embryos ranging in age from 18 to 32 hours were treated with thymidine‐H3 to examine the cell cycle and nuclear migration of the neuro‐epithelial cells during closure of the neural tube.

By plotting the percentage of labeled metaphases against the tune of thymidine‐H3 application, the DNA‐synthetic period was found to last five hours, the postduplication (G2) stage and prophase two and one‐half hours and the preduplication (G1) stage to be brief or non‐existent. The total cell cycle time was calculated to be eight hours. During DNA synthesis the nuclei are located near the basement membrane; subsequently they migrate to the lumen to undergo mitosis, after which they return to the outer zone to start DNA synthesis for the next cell division.

To determine the life span of the neuro‐epithelial cells by a different method, chick embryos were treated with vincristine, a drug known to arrest the mitosis in the metaphase. Fifteen, 26, 34 and 41% of the neuro‐epithelial cells were arrested in the metaphase, one, two, three and four hours after treatment, respectively. Since the “mitotic index” of the neuro‐epithelial cells was 5.2, the duration of the mitosis was calculated to last 25 minutes, and the life span of the neuro‐epithelial cell to be eight hours.

Immediately after closure of the neural tube, a different cell type characterized by a round nucleus, pale nucleoplasm and a dark‐staining nucleolus appeared at the periphery of the tube near the basement membrane. These cells, which originate by division from the neuro‐epithelial cells at the lumen, did not incorporate thymidine‐H3 at any time during further development. They are considered to be primitive neuroblasts and to form the first representatives of the mantle layer.
A comparative study of the reticular formation of the guinea pig
Authors: Petrovicky Pavel
Published: January 2005

The author investigated the reticular formation in the guinea pig, using one sagittal and three frontal series of the brain stem stained according to the method of Nissl. The nuclei of the reticular formation in the guinea pig were identified and mapped.

In the second part of the work the author compared the individual nuclei of the reticular formation in nine representatives of five orders of mammals: primates, carnivores, rodents, insectivores and chiroptera. A table illustrates the occurrence of reticular nuclei in the orders studied.
H3‐Thymidine autoradiographic studies on the cell proliferation and differentiation in the external and the internal granular layers of the mouse cerebellum
Authors: Fujita Setsuya , Shimada Morimi , Nakamura Tuneo
Published: January 2005

Cell proliferation and migration in the external granular layer of the mouse cerebellum were studied with autoradiography after cumulative labeling with H3‐thymidine. The germinative cells in the external granular layer were considered as externally dislocated matrix cells. Their generation time, presynthetic time, duration of DNA synthesis, postsynthetic time and mitotic time were determined in one‐, three‐, seven‐ and ten‐day‐old mice. The entire sequence of the ontogeny of the external granular cell‐system was separated into three consecutive stages; stage 1 or stage of pure external matrix cell proliferation, stage 2 or stage of neuroblast production, and stage 3 or stage of neuroglia differentiation. Production of neuroblasts in the external granular layer at seven and ten days of life and their migration into the internal granular layer were demonstrated by means of autoradiography. Transit times of the neuroblasts migrating across the external mantle layer and the molecular layer of ten‐day‐old mice were estimated at 21 and four hours, respectively. More than 50% of the inner granular cells migrated from the external granular layer later than ten days of life and almost 81 to 92% were produced later than seven days of postnatal life. In conclusion, on the basis of the matrix cell concept, the authors tried to unify observations of previous and present investigators and presented a scheme of pre‐ and postnatal histogenesis of the mouse cerebellum.
Comparative fine structure of vertebrate neuroglia: Teleosts and reptiles
Authors: Kruger Lawrence , Maxwell David S.
Published: January 2005

Electron microscopic examination of aldehyde perfused fish and reptile brains reveals the presence of three distinct varieties of glial elements; ependyma, astrocytes and oligodendrocytes. Ependymal cells line the ventricular cavity, possess cilia and extend long fibrillar processes to the pial surface. Several cytoplasmic organelles and specialized plasma membrane contacts are unique to this glial variety. Astrocytes possess long processes which can be traced as pericapillary and sub‐pial end‐feet. Their cytoplasm contains fine filaments (less than 100 Å) and quantities of glycogen granules. Oligodendrocytes display only occasional long processes and usually have thin cytoplasmic rims, especially when related to myelinated axons. A wide range of nuclear and cytoplasmic matrix densities, numerous free ribosomes and an extensive microtubular system characterize these cells. On the basis of distinctive cytoplasmic organelles it appears possible to establish the homology of lower vertebrate and mammalian glial elements.
Cortical projections from the dorsal lateral geniculate nucleus of cats
Authors: Glickstein Mitchell , King Richard A. , Miller Josef , Berkley Mark
Published: January 2005

Lesions were placed in the dorsal lateral geniculate nucleus of cats (LGN) and cortical degeneration studied with a modified Nauta method. Besides local degeneration attributable to the electrode track, dense projections to Areas 17 and 18 ipsilateral to the lesion were found. Medium or dense degeneration was found on both banks of the suprasylvian fissure ipsilaterally and light degeneration widely distributed in Area 19 and on the suprasylvian and posterior ectosylvian gyri. In addition to commissural degeneration homotopic to the electrode track, degenerating fibers were found in the visual areas of the opposite hemisphere, suggesting the presence of a crossed geniculo‐cortical pathway.