bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical genetic analysis of Parkinson's disease in the contursi kindred
Authors: Golbe Lawrence I. , Lazzarini Alice M. , Duvoisin Roger C. , Iorio Giuseppe Di , Sanges Giuseppe , Bonavita Vincenzo , la Sala Salvatore 
Published: January 2005

AbstractWe performed a clinical genetic analysis of a kindred originating in the town of Contursi in Salerno province, Italy, in which 60 individuals in 5 generations are known to have had Parkinson's disease (PD). Two previously reported autopsy cases showed typical PD with Lewy bodies. The inheritance pattern is apparenly autosomally dominant with a segregation ratio of 40.1% for kindred members aged 50 years and older. The mean age at PD onset is 45.6 years (standard deviation, 13.48; range, 20–85) with a mean course to death of 9.2 years (standard deviation, 4.87; range, 2–20). Otherwise, clinical characteristics of PD in the kindred, including variance in onset age and incidence of tremor and levodopa responsiveness, are similar to those of PD in the community. The presence of tremor tended to be concordant in affected parent‐child pairs, but there was no parent‐child correlation for age at onset or intrasibship clustering of tremor or onset age. A suggestin of anticipation disappeared after adjustment for age‐relted ascertainment bias. The findings show that a presumably single mutation can prodcue a heterogeneous PD phenotype, even among siblings. This is consistent with the hypothesis that PD in the community may in fact be caused by sch a mutation, but one producing a lower penetrance and older age at onset than those in this kindred.
Interferon beta‐1b inhibits gelatinase secretion and in vitro migration of human T cells: A possible mechanism for treatment efficacy in multiple sclerosis
Authors: Leppert David , Waubant Emmanuelle , Bürk Martin R. , Oksenberg Jorge R. , Hauser Stephen L. 
Published: January 2005

AbstractTreatment with interferon beta‐1b has substantial clinical benefit in the demyelinating disease multiple sclerosis, yet the mechanism of action in the disease remains largely unknown. Gelatinase A (matrix metalloproteinase‐2, 72‐kd gelatinase) and B (matrix metalloproteinase‐9, 92‐kd gelatinase) are matrix metalloproteinases capable of enzymatic digestion of subendothelial basement membrane constituents. In human T cells, interleukin‐2 induces gelatinase secretion and enhances gelatinase‐dependent migration across an artificial basement membrane‐like layer in vitro. Pretreatment of T cells with interferon beta‐lb for 48 hours decreased interleukin‐2‐induced gelatinase production and secretion as determined by zymography. In parallel to the downregulation of gelatinase secretion, pretreatment with interferon beta‐lb inhibited T‐cell migration across the basement membrane in vitro by up to 90%, but had only a minor impact on cell locomotion per se. For both gelatinase secretion and T‐cell migration, the inhibitory effect mediated by exposure to interferon beta‐1b was dose dependent. Fluorescence‐activated cell sorter analysis also showed that interferon beta‐1b downregulates the interleukin‐2 receptor α‐chain and lowered the affinity of interleukin‐2 to the cell surface by 30%, which may represent an additional mechanism for the observed effects of interferon beta‐1b. The dramatic effects of interferon beta‐1b on gelatinase expression and migration raise the possibility that its beneficial effects in multiple sclerosis may result from interference with the capacity of activated T cells to traverse the basement membrane and migrate to the central nervous system.
The Clinical phenotype of two missense mutations in the presenilin I gene in Japanese patients
Authors: Ikeda Masaki , Sharma Vikram , Mark Sumi S. , Rogaeva Ekaterina A. , Poorkaj Parvoneh , Sherrington Robin , Nee Linda , Tsuda Takehide , Oda Nobuhito , Watanabe Mitsunori , Aoki Masashi , Shoji Mikio , Abe Koji , Itoymia Yasuto , Hirai Shurisaku , Schellenberg Gerard D. , Bird Thomas D. , George‐Hyslop P. H. St 
Published: January 2005

AbstractWe report the clinical and neuropathologic phenotypes associated with two different missense mutations in the presenilin 1 (PS‐1) gene in Japanese patients with early‐onset familial Alzheimer's disease (FAD). In the Ah4/JPN1 pedigree a missense mutation (C→T) was found at nucleotide 1102, which is predicted to cause an alanine‐to‐valine missense substitution at codon 260. In this family, the disease had a mean age of onset of 40.3 years and an indolent course (range, 8–19 years). Neuropathologic studies in 3 members of this pedigree showed widespread senile plaques, neurofibrillary tangles, and neuronal loss, as well as abundant perivascular subpial amyloid deposits in the Virchow‐Robin spaces and the presence of Pick‐like intraneuronal inclusions in the dentate gyrus. In the second pedigree, transmitting a C→T nucleotide substitution at position 1027, leading to the missense mutation of alanine to valine at codon 285, the disease had a later onset (mean, 51 years) but a more rapid course. Comparison of the disease phenotypes associated with other missense mutations in exon 9 of PS‐1 reveals no clinical or pathological phenotype, which uniquely distinguishes Alzheimer's disease associated with PS‐1 mutations from other forms of early‐onset FAD, implying that direct mutation screening is required to identify these cases.
Clinical and pathological features in hydrocarbon‐induced Parkinsonism
Authors: Pezzoli G. , Strada O. , Silani V. , Zecchinelli A. , Perbellini L. , Javoy‐Agid F. , Ghidoni P. , Motti E. D. F. , Masini T. , Scarlato G. , Agid Y. , Hirsch E. C. 
Published: January 2005

AbstractA neuropathological examination was performed on a patient with parkinsonism induced by prolonged exposure to a mixture of aliphatic hydrocarbons, mainly n‐hexane and halogenated compounds. The patient developed a rapid‐course disease that progressed even after with‐drawal from the toxic exposure. Pathological examination and immunohistochemical analysis of the brain revealed severe and widespread dopaminergic neuronal loss, associated with severe gliosis, in the substantia nigra, and almost complete loss of tyrosine hydroxylase immunostaining in the striatum. No Lewy bodies were detected. Neuronal loss was also observed in the periaqueductal gray matter, locus ceruleus, and pedunculopontine nucleus. These changes, combined with the moderate anemia due to marrow suppression, and the mild axonal neuropathy observed in vivo, are suggestive of a hydrocarbon toxic insult.
Familial episodic ataxia: Clinical heterogeneity in four families linked to chromosome 19p
Authors: Baloh Robert W. , Yue Qing , Furman Joseph M. , Nelson Stanley F. 
Published: January 2005

AbstractWe describe the clinical and oculographic findings in 4 families with episodic ataxia and interictal nystagmus (EA‐2) linked to chromosome 19p. Episodes varied from pure ataxia to combinatins of symptoms suggesting involvement of the cerebellum, brainstem, and cortex. Some affected individuals exhibited a progressive ataxia syndrome phenotypically indistiguishable from the dominantly inherited spinocerebellar ataxia (SCA) syndromes. About one‐half of the affected individuals had migraine headaches and several had episodes typical of basilar migraine. Oculographic findings were localizing to the vestibulocerebellum and posterior vermis. Additional genetic and environmental factors must account for the marked clinical heterogeneity in these families with an abnormal gene on chromosome 19p.
Activation mapping in essential tremor with functional magnetic resonance imaging
Authors: Bucher Stefan F. , Seelos Klaus C. , Dodel Richard C. , Reiser Maximilian , Oertel Wolfgang H. 
Published: January 2005

AbstractWe used functional magnetic resonance imaging (FMRI) to study possible cerebral activation patterns associated with unilateral postural tremor in 12 patients with essential tremor (ET), with mimicked postrual tremor in 15 control subjects, and with passive wrist oscillation in both groups. During essential tremor, patients showed mainly contralateral activation of the primary motor and primary sensory areas, the globus pallidus, and the thalamus, but bilateral activation of the nucleus dentatus, the cerebellar hemispheres, and the red nucleus. Only 2 patients presented with activity in the medulla close to the olivary nucleus. Unilateral passive wrist oscillation of ET patients resulted in only unilateral activation of the cerebellum, nuclei dentati, and red nuclei. In contrast to the involuntary tremor condition of ET patients, the mimicked tremor condition of the control subjects was not associated with bilateral activity in the cerebellum, nuclei dentati, or red nuclei. Involuntary tremor of ET patients was associated with a significantly larger extent of activation in the cerebellar hemispheres and the red nucleus (p < 0.003) compared with mimicked tremor in the control group. Our FMRI study indicates that ET is mainly associated with an additional contralateral cerebellar pathway activation and overactivity in the cerebellum, red nucleus, and globus pallidus without significant intrinsic olivary activation.
Which clinical sign of Parkinson's disease best reflects the nigrostriatal lesion?
Authors: Vingerhoets Francois J. G. , Schulzer Michael , Calne Donald B. , Snow Barry J. 
Published: January 2005

AbstractClinical scales, based on the major signs of Parkinson's disease (PD), are commonly used to assess the effect of symptomatic treatment of PD. With the appearance of therapy aiming to rescue or protect the nigrostriatal neurons in PD, it becomes essential to define which of these signs best reflects the underlying neuronal deficit. Fluorodopa positron emission tomography has been shown to correlate with postmortem nigral cell counts. We correlated the major signs of PD with positron emission tomography results in 35 PD patients. We found that in the “practically defined off” state, (1) Purdue pegboard scores correlated best with the nigrostriatal dopaminergic deficit; (2) of the subscales of the modified Columbia score, the bradykinesia subscale correlated best; (3) rigidity and postural distrubance correlated less highly than bradykinesia, and their inclusion in a multiple regression did not improve the correlation of pegboard or bradykinesia scores alone; and (4) tremor did not correlate with the nigrostriatal dopaminergic deficit. We conclude that pegboard and bradykinesia scores represent the best clinical measures for studying the effect of treatment on the evolution of the nigrostriatal lesion of PD. Inclusion of other clinical signs provides additional information only for the study of functional impairments.
Inclusion body myositis and paraproteinemia: Incidence and immunopathologic correlations
Authors: Dalakas Marinos C. , Illa Isabel , Gallardo Eduard , Juarez Candido 
Published: January 2005

AbstractSerum from 70 patients with sporadic inclusion body myositis (IBM) was subjected to agarose gel immunofixation electrophoresis. The IgG extracted from 9 patients with monoclonal proteins, 3 without, and 2 control subjects and was purified, biotinylated, and applied to muscle biopsy sections for immunocytochemistry and to purified muscle protein fractions for immunoblots. Sixteen of 70 (22.8%) patients with IBM, compared with 2% of agematched controls, had a monoclonal gammopathy characterized as IgGλ in 9 patients, IgGk in 4, IgMk in 2, and IgAλ in 1. The mean age of IBM patients with gammopathy was 60.6 years (range, 35–77 years), compared with 66.1 years (range, 42–80 years) of the IBM patients without gammopathy. The IgG of the patients, more often than that of the control subjects, immunostained myonuclei and recognized various muscle proteins of 35 to 145 kd. We conclude that IBM, regardless of age, is frequently associated with monoclonal gammopathies, which often recognize various muscle components, especially myonuclei, suggesting disturbed immunoregulation.
Collection and normal levels of the amyloid precursor protein in plasma
Authors: Whyte Scott , Wilson Neil , Currie Jon , Maruff Paul , Malone Valencia , ‐Antonacci Ruxsana Shafiq , Tyler Peter , Derry Kathryn L. , Underwood John , Li Qiao‐Xin , Beyreuther Konrad , Masters Colin L. 
Published: January 2005

AbstractThe amyloid precursor protein is contained in plantelet alpha granules and released with degranulation. Methods are described to control for amyloid precursor protein release from platelets during blood collection and processing. In normal subjects (n = 97; age range, 44–84 years), the average plasma level of amyloid precursor protein was 6.5 ± 1.8 ng/ml.
Energy metabolism defects in Huntington's disease and effects of coenzyme Q10
Authors: Koroshetz Walter J. , Jenkins Bruce G. , Rosen Bruce R. , Beal M. Flint 
Published: January 2005

AbstractWe investigated whether the Huntington's desease (HD) gene mutation may produce either primary or secondary effects on energy metalbolism. 31P magnetic resonance spectroscopy demonstrated a significant decrease in the phosphocreatine to inorganic phosphate ratio in resting muscle of 8 patients as compared with 8 control subjects. The cerebrospinal fluid lactate‐pyruvate ratio was significantly increased in 15 patients as compared with 13 control subjects. Lactate concentrations assessed using 1H magnetic resonance spectroscopy are increased in Huntington's disease cerebral cortex. Treatment with coenzyme Q10, an essential cofactor of the electron transport chain, resulted in significant decreases in cortical lactate concentrations in 18 patients, which reversed following withdrawal of therapy. These findings provide evidence for a generalized energy defect in Huntington's disease, and suggest a possible therapy.
Pupil‐involving third‐nerve palsy and carotid stenosis: Rapid recovery following endarterectomy
Authors: Balcer L. J. , Galetta S. L. , Yousem D. M. , Golden M. A. , Asbury A. K. 
Published: January 2005

AbstractWe report a patient who presented with a painful pupil‐involving third‐nerve palsy. Cerebral angiography revealed a high‐grade stenosis of the ipsilateral internal carotid artery with a 4‐cm intraluminal thrombus. Following emergent carotid endarterectomy, the patient's partial third‐nerve palsy resolved in 1 hour. A pupil‐involving third‐nerve palsy may be an unusual presentation of impending carotid occlusion.
Treatment of ramsay hunt syndrome with acyclovir‐prednisone: Significance of early diagnosis and treatment
Authors: Murakami Shingo , Hato Naohito , Horiuchi Joji , Honda Nobumitsu , Gyo Kiyofumi , Yanagihara Naoaki 
Published: January 2005

AbstractAlthough the antiviral agent acyclovir is currently used for the treatment of Ramsay Hunt syndrome, its effects on facial nerve and hearing recovery remain controversial. We retrospectively analyzed the effects of acyclovir‐prednisone treatment in 80 Ramsay Hunt patients. Of 28 patients for whom treatment was begun within 3 days of the onset of facial paralysis, the recovery from paralysis was complete in 21 (75%). By comparison, of 23 patients for whom treatment was begun more than 7 days after onset, recovery from facial paralysis was complete in only 7 (30%). A significant difference in facial nerve recovery was found between these groups. Early administration of acyclovir‐prednisone was proved to reduce nerve degeneration by nerve excitability testing. Hearing recovery also tended to be better in patients with early treatment. There was no significant difference in facial nerve outcome between intravenous and oral acyclovir treatment.
Imaging of δ‐ and μ‐opioid receptors in temporal lobe epilepsy by positron emission tomography
Authors: Madar Igal , Lesser Ronald P. , Krauss Gregory , Zubieta Jon Kar , Lever John R. , Kinter Chris M. , Ravert Hayden T. , Musachio John L. , Mathews William B. , Dannals Robert F. , Frost J. James 
Published: January 2005

AbstractThe involvement of opioid neurotransmitter systems in seizure mechanisms is well documented. In previous positron emission tomography (PET) studies in patients with unilateral temporal lobe epilepsy, we have found evidence for differential regulation of the opioid‐receptor subtypes. The present study extends our previous observations to δ‐opioid receptors by using the δ‐receptor‐selective antagonist [11C]methylnatrindole ([11C]MeNTI). Paired measurements of δ‐ and μ‐opioid receptor binding and metabolic activity were performed with PET using [11C]MeNTI and [11C]carfentanil ([11C]CFN) and [18F]fluorodeoxyglucose ([18F]FDG), respectively. Binding of [11C]MeNTI and [11C]CFN increased and [18F]FDG uptake decreased in the temporal cortex (TC) ipsilateral to the focus. Decreases in [18F]FDG uptake were more widespread regionally than were increases in opioid receptors. Increases in the δ‐ and μ‐receptor binding showed different regional patterns. Increases in δ‐receptor binding were confined to the middle aspect of the inferior TC, whereas binding of δ receptors increased in the mid‐inferior TC and anterior aspect of the middle and superior TC. The increase in δ receptors suggests their anticonvulsant action, as previously shown for the δ‐receptor subtype, whereas the different regional pattern of receptor alterations suggest the distinct roles of different opioid‐receptor subtypes in seizure phenomena.
Use of desferrioxamine in the treatment of aceruloplasminemia
Authors: Miyajima Hiroaki , Takahashi Yoshitomo , Kamata Tadashi , Shimizu Hideaki , Sakai Naoki , Gitlin Jonathan D. 
Published: January 2005

AbstractAceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism resulting in neurodegeneration of the retina and basal ganglia. We report here on the treatment of a patient who developed progressive extrapyramidal symptoms that included blepharospasm, grimacing, and rigidity associated with increased iron deposition in the brain and visceral organs. Treatment for 10 months with the iron chelator desferrioxamine decreased brain iron stores, prevented progression of the neurological symptoms, and reduced plasma lipid peroxidation. These data suggest that early treatment with this chelator may be useful in such patients to diminish central nervous system iron accumulation and to prevent or ameliorate neurological symptoms associated with neurodegeneration.
Midbrain dopaminergic neuronal degeneration in a transgenic mouse model of familial amyotrophic lateral sclerosis
Authors: Kostic V. , Gurney M. E. , Deng H.‐X. , Siddique T. , Epstein C. J. , Przedborski S. 
Published: January 2005

AbstractFamilial amyotrophic lateral sclerosis has been linked in 15% of families to mutations in the gene encoding for copperzinc superoxide dismutase (Cu/Zn‐SOD), a key enzyme in the cellular defense mechanisms against free radical attack. We used a transgenic mouse model of familial amyotrophic lateral sclerosis (transgenic G1H mice) based on expression of mutant human Cu/Zn‐SOD to examine the influence of the transgene expression on midbrain dopaminergic neurons, cells that contain conspicuous amounts of this enzyme. At the time that 50% of motor neurons of the spinal cord were lost, we observed concurrent reductions in dopamine levels in the caudate‐putamen and the nucleus accumbens of transgenic G1H mice. In addition, numbers of tyrosine hydroxylase‐immunostained neurons were significantly reduced in both the substantia nigra (26%) and the ventral tegmental area (16%) compared to those in their nontransgenic littermates. Similar abnormalities were not observed in the brains of transgenic mice overexpressing wild‐type Cu/Zn‐SOD. These findings indicate that overexpression of the mutated Cu/Zn‐SOD protein caused a significant loss of midbrain dopaminergic neurons in addition to the loss of spinal motor neurons. The potential of the mutated enzyme to induce cell death extending beyond the motor neurons is consistent with the description of substantia nigra degeneration in some patients with familial amyotrophic lateral sclerosis. Furthermore, if mutated Cu/Zn‐SOD is conclusively shown to kill cells by oxidative stress, such an observation would be in keeping with the known sensitivity of dopaminergic neurons to free radical attack.
Immunochemical analysis of dopamine transporter protein in Parkinson's disease
Authors: Miller Gary W. , Staley Julie K. , Heilman Craig J. , Perez Jeffrey T. , Mash Deborah C. , Rye David B. , Levey Allan I. 
Published: January 2005

AbstractThe plasma membrane dopamine transporter (DAT) is considered to be a reliable marker of presynaptic dopaminergic terminal loss. Previous in vivo imaging and postmortem binding studies have detected a loss in striatal DAT binding in Parkinson's diseased (PD) brain; however, these techniques have poor spatial resolution and may suffer from nonspecific binding of some ligands. In this study, we use novel highly specific monoclonal antibodies to distinct epitopes of human DAT to quantify and localize the protein. Western blot analysis revealed marked reductions in DAT immunoreactivity in putamen, caudate, and nucleus accumbens of PD brain compared with control cases, and the reductions were significantly correlated to disease duration. Immunohistochemistry revealed DAT‐immunoreactive fibers and puncta that were dense throughout the striatum of control brains but that were drastically reduced in putamen of PD brains. Caudate from PD brains showed a significant degree of sparing along the border of the ventricle, and the nucleus accumbens was relatively preserved. An unexpected finding was that discrete islands of DAT immunoreactivity were preserved within the matrix of PD putamen. Thus, immunological analysis of DAT protein provides novel and sensitive means for localizing and quantifying DAT protein in PD and other neurological disorders involving dopaminergic systems.
Regional and cellular expression of the dentatorubral‐pallidoluysian atrophy gene in brains of normal and affected individuals
Authors: Nishiyama K. , Nakamura K. , Murayama S. , Yamada M. , Kanazawa I. 
Published: January 2005

AbstractDentatorubral‐pallidoluysian atrophy is an autosomal dominant neurodegenerative disorder characterized by dementia and spinocerebellar degeneration. Recently, part of the gene responsible for this disorder was cloned containing a CAG repeat, and predominant neuronal expression of the gene was proved only through Northern blot analysis in rats. In this study, we investigated the regional and cellular expression of the dentatorubral‐pallidoluysian atrophy gene in the central nervous system of normal and affected humans, as well as in rat brains. In normal control human subjects, the gene messenger RNA was present in all brain regions examined, with the highest levels seen in the cerebellum, hippocampus, substantia nigra, and pontine nuclei. Its expression in the striaum, globus pallidus, and cerebral cortex was intermediate. The gene was expressed predominantly in neurons; a low but significant level of expression was also seen in glial cells. Neurons susceptible to degeneration in dentatorubral‐pallidoluysian atrophy did not selectively express high or low levels of its gene messenger RNA. In brains affected by the disorder, the distribution and levels of gene messenger RNA were comparable to those of the normal controls in all the areas. In the rat brains, gene messenger RNA expression was very similar to that in human brain. It was also expressed predominantly in neurons, while low‐level expression was observed in glial cells. It is apparent from these results that the presence of expanded trinucleotide repeats in dentatorubral‐pallidoluysian atrophy does not result in the absence of its gene messenger RNA expression or in altered patterns or levels of expression.