bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endocytic disturbances distinguish among subtypes of alzheimer's disease and related disorders
Authors: Cataldo Anne , Rebeck G. William , Ghetti Bernadino , Hulette Christine , Lippa Carol , Van Broeckhoven Christine , Van Duijn Cornelia , Cras Patrick , Bogdanovic Nenad , Bird Thomas , Peterhoff Corrinne , Nixon Ralph 
Published: November 2004

AbstractThe endocytic pathway is important in amyloid precursor protein (APP) processing and β‐amyloid formation. Our studies have shown that endocytic pathway activation is a prominent and early feature of neurons in vulnerable regions of the brain in sporadic Alzheimer's disease. We report that endocytic pathway abnormalities are present not only in neurons, but in cerebral endothelia in Alzheimer's disease caused by certain APP mutations. The presence or absence of endocytic abnormalities distinguish subtypes of familial Alzheimer's disease linked to APP mutations from presenilin mutations, supporting the notion that different cellular pathways are involved in the altered processing of APP leading to increased β‐amyloid generation in certain of these different Alzheimer's disease subtypes.
Nonprogressive autosomal recessive ataxia maps to chromosome 9q34‐9qter in a large consanguineous lebanese family
Authors: Delague Valérie , Bareil Corinne , Bouvagnet Patrice , Salem Nabiha , Chouery Eliane , Loiselet Jacques , Mégarbané André , Claustres Mireille 
Published: November 2004

AbstractCongenital ataxias are a heterogeneous group of predominantly nonprogressive disorders characterized by hypotonia, developmental delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum. We performed a genome‐wide screen on a large inbred Lebanese family presenting a nonprogressive autosomal recessive congenital cerebellar ataxia associated with short stature (MIM 213200), already described by Mégarbané and colleagues.1 The disease locus was assigned to a 12.1 cM interval on chromosome 9q34‐9qter between D9S67 and D9S312. Differential diagnosis with other hereditary ataxias linked to the same region is discussed.
Central and peripheral nervous system infection, immunity, and inflammation in the nonhuman primate model of lyme borreliosis
Authors: Pachner Andrew R. , Cadavid Diego , Shu Gale , Dail Donna , Pachner Sarah , Hodzic Emir , Barthold Stephen W. 
Published: November 2004

AbstractThe relationship between chronic infection, antispirochetal immunity, and inflammation is unknown in Lyme neuroborreliosis. In the nonhuman primate (NHP) model of Lyme neuroborreliosis, we measured spirochetal density in the nervous system and other tissues by polymerase chain reaction and correlated these values to anti‐B. burgdorferi antibody in the serum and cerebrospinal fluid, and to inflammation in tissues. Despite substantial presence of B. burgdorferi, the causative agent of Lyme borreliosis, in the central nervous system, only minor inflammation was present there, though skeletal and cardiac muscle, which contained similar levels of spirochete, were highly inflamed. Anti‐B. burgdorferi antibody was present in the cerebrospinal fluid but was not selectively concentrated. All infected animals developed anti‐B. burgdorferi antibody in the serum, but increased amplitude of antibody was not predictive of higher levels of infection. These data demonstrate that Lyme neuroborreliosis is a persistent infection, that spirochetal presence is a necessary but not sufficient condition for inflammation, and that antibody measured in serum may not predict the severity of infection.
European/Canadian multicenter, double‐blind, randomized, placebo‐controlled study of the effects of glatiramer acetate on magnetic resonance imaging–measured disease activity and burden in patients with relapsing multiple sclerosis
Authors: Comi Giancarlo , Filippi Massimo , Wolinsky Jerry S. ,   European/Canadian Glatiramer Acetate Study Group
Published: November 2004

AbstractTwo prior double‐blind, placebo‐controlled, randomized trials demonstrated that glatiramer acetate (GA) reduces relapse rates in patients with relapsing remitting multiple sclerosis (RRMS). This study was designed to determine the effect, onset, and durability of any effect of GA on disease activity monitored with magnetic resonance imaging (MRI) in patients with RRMS. Two hundred thirty‐nine eligible patients were randomized to receive either 20 mg GA (n = 119) or placebo (n = 120) by daily subcutaneous injection. Eligibility required one or more relapses in the 2 years before entry and at least one enhancing lesion on a screening MRI. The study was a randomized, double‐blind, placebo‐controlled phase during which all patients studied underwent monthly MRI scans and clinical assessments over 9 months. The primary outcome measure was the total number of enhancing lesions on T1‐weighted images. Secondary outcome measures included the proportion of patients with enhancing lesions, the number of new enhancing lesions and change in their volume; the number of new lesions detected on T2‐weighted images and change in their volume, and the change in volume of hypointense lesions seen on unenhanced T1‐weighted images. Clinical measures of disease activity were also evaluated. The active treatment and placebo groups were comparable at entry for all demographic, clinical, and MRI variables. Treatment with GA showed a significant reduction in the total number of enhancing lesions compared with placebo (−10.8, 95% confidence interval −18.0 to −3.7; p = 0.003). Consistent differences favoring treatment with GA were seen for almost all secondary end points examined: number of new enhancing lesions (p < 0.003), monthly change in the volume of enhancing lesions (p = 0.01), and change in volume (p = 0.006) and number of new lesions seen on T2‐weighted images (p < 0.003). The relapse rate was also significantly reduced by 33% for GA‐treated patients (p = 0.012). All effects increased over time. Glatiramer acetate significantly reduced MRI‐measured disease activity and burden. Ann Neurol 2001;49:290–297
Differences in sensory and motor cortical organization following brain injury early in life
Authors: Thickbroom Gary W. , Byrnes Michelle L. , Archer Sarah A. , Nagarajan Lakshmi , Mastaglia Frank L. 
Published: November 2004

AbstractThere have been a number of physiological studies of motor recovery in hemiplegic cerebral palsy which have identified the presence of novel ipsilateral projections from the undamaged hemisphere to the affected hand. However, little is known regarding the afferent projection to sensory cortex and its relationship to the reorganized cortical motor output. We used transcranial magnetic stimulation (TMS) to investigate the corticomotor projection to the affected and unaffected hands in a group of subjects with hemiplegic cerebral palsy, and also performed functional magnetic resonance imaging (fMRI) studies of the patterns of activation in cortical motor and sensory areas following active and passive movement of the hands. Both TMS and fMRI demonstrated a normal contralateral motor and sensory projection between the unaffected hand and the cerebral hemisphere. However, in the case of the affected hand, the TMS results indicated either a purely ipsilateral projection or a bilateral projection in which the ipsilateral pathway had the lower motor threshold, whereas passive movement resulted in fMRI activation in the contralateral hemisphere. These results demonstrate that there is a significant fast‐conducting corticomotor projection to the affected hand from the ipsilateral hemisphere in this group of subjects, but that the predominant afferent projection from the hand is still directed to the affected contralateral hemisphere, resulting in an interhemispheric dissociation between afferent kinesthetic inputs and efferent corticomotor output. The findings indicate that there can be differences in the organization of sensory and motor pathways in cerebral palsy, and suggest that some of the residual motor dysfunction experienced by these subjects could be due to an impairment of sensorimotor integration at cortical level as a result of reorganization in the motor system. Ann Neurol 2001;49:320–327
Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial Parkinsonism associated with mutations in the Parkin gene
Authors: Hilker Ruediger , Klein Christine , Ghaemi Mehran , Kis Bernhard , Strotmann Tim , Ozelius Laurie J. , Lenz Olaf , Vieregge Peter , Herholz Karl , Heiss Wolf‐Dieter , Pramstaller Peter P. 
Published: November 2004

AbstractA kindred from South Tyrol (northern Italy) with familial, adult‐onset parkinsonism of pseudo‐dominant inheritance and mutations in the parkin gene was recently described. To gain insight into basal ganglia dysfunction in this form of hereditary parkinsonism, positron emission tomography (PET) with 18‐fluorodopa (FDOPA) and 11C‐raclopride (RAC) was performed in 5 affected family members and 5 asymptomatic relatives with proven compound heterozygous or heterozygous parkin mutations. Results were compared to findings in healthy control subjects and patients with typical sporadic, idiopathic Parkinson‘s disease. Similar to findings in the sporadic Parkinson’s disease group, presynaptic striatal FDOPA storage was decreased in patients with compound heterozygous parkin mutations, with the most prominent reduction in the posterior part of the putamen. Along with the presynaptic lowered FDOPA uptake, we found a uniform reduction of the striatal 11C‐raclopride binding index in all affected family members as compared to asymptomatic family members carrying a heterozygous parkin mutation, sporadic Parkinson's disease, and control subjects. Our PET data provide evidence that parkinsonism in this family is associated with presynaptic dopaminergic dysfunction similar to idiopathic Parkinson's disease pathophysiology, along with alterations at the postsynaptic D2 receptor level. In asymptomatic carriers of a single parkin mutation with an apparently normal allele, we found a mild but statistically significant decrease of mean FDOPA uptake compared to control subjects in all striatal regions. These data indicate a preclinical disease process in these subjects. Ann Neurol 2001;49:367–376
The incidence of mitochondrial encephalomyopathies in childhood: Clinical features and morphological, biochemical, and DNA abnormalities
Authors: Darin Niklas , Oldfors Anders , Moslemi Ali‐Reza , Holme Elisabeth , Tulinius Már 
Published: November 2004

AbstractIn this study we present incidence, point prevalence, and mortality figures of mitochondrial encephalomyopathies in a population‐based study of children from western Sweden. Through the screening of registers and review of medical records, we identified 32 patients under 16 years of age from the study population who were diagnosed between January 1, 1984, and December 31, 1998. The incidence of mitochondrial encephalomyopathies in preschool children (<6 years of age) was 1 out of 11,000. The preschool incidence of Leigh's syndrome was 1 out of 32,000, and the preschool incidences of both Alper's syndrome and infantile mitochondrial myopathy with cytochrome C oxidase deficiency were 1 out of 51,000. The point prevalence (January 1, 1999) of mitochondrial encephalomyopathies in children under 16 years of age was 1 out of 21,000. The median survival for patients with infantile onset was until 12 years of age. We identified 4 cases with mitochondrial DNA point mutations, 2 cases with mitochondrial DNA deletions, and 2 cases with nuclear mutations in the SURF1 gene. We conclude that mitochondrial encephalomyopathies are relatively common neurometabolic disorders in childhood. Ann Neurol 2001;49:377–383
Neurological and neuropathologic heterogeneity in two brothers with cobalamin C deficiency
Authors: Powers James M. , Rosenblatt David S. , Schmidt Robert E. , Cross Anne H. , Black Joseph T. , Moser Ann B. , Moser Hugo W. , Morgan Daniel J. 
Published: November 2004

AbstractTwo adult brothers, one documented to have methylmalonic acidemia with homocystinuria, or cobalamin C deficiency, after autopsy, displayed severe but divergent neurological presentations. One exhibited a myelopathy and the other chronic endocrine problems (Schmidt's syndrome) followed by a neuropsychiatric and dementing disorder owing to cerebral perivascular demyelination. The recognition of cobalamin C deficiency has practical implications because it is one of the few inherited diseases of central white matter that is treatable. Ann Neurol 2001;49:396–400
Anticardiolipin antibodies are not a useful screening tool in a nonselected large group of patients with multiple sclerosis
Authors: Sastre‐Garriga Jaume , Reverter Juan Carlos , Font Josep , Tintoré Mar , Espinosa Gerard , Montalban Xavier 
Published: November 2004

AbstractRecent works claiming that primary antiphospholipid syndrome (PAPS) cannot be clinically distinguished from multiple sclerosis (MS) recommend that MS patients be screened for anticardiolipin antibodies (ACA). In this study 296 randomly selected patients with MS and clinically isolated syndromes and 51 healthy controls were analyzed; ACA, anti‐β2‐glycoprotein I, or antiprothrombin was found in 6 patients. No predominance of any kind of clinical manifestations and no cardinal manifestations of PAPS were found in these patients. ACA tests should be performed only when a suspicion of PAPS is raised and atypical clinical presentation for MS is found. Ann Neurol 2001;49:408–411
Primary progressive aphasia
Authors: Mesulam M.‐Marsel 
Published: November 2004

AbstractPrimary progressive aphasia (PPA) is a focal dementia characterized by an isolated and gradual dissolution of language function. The disease starts with word‐finding disturbances (anomia) and frequently proceeds to impair the grammatical structure (syntax) and comprehension (semantics) of language. The speech output in PPA can be fluent or nonfluent. Memory, visual processing, and personality remain relatively well‐preserved until the advanced stages and help to distiguish PPA from frontal lobe dementia and the typical forms of Alzheimer's disease. The term “semantic dementia” was originally introduced to designate a different group of patients with a combination of verbal and visual processing deficits. In practice, however, this diagnosis is also being used in a variant sense to denote a subtype of PPA with fluent speech and impaired comprehension, even in the absence of visual processing deficits. Insofar as the diagnosis of semantic dementia can have these two different meanings, it is important to specify whether it is being used in the original sense or to denote a subtype of PPA. Structural and physiological neuroimaging confirms the selective predilection of PPA for the left hemisphere, especially for its language‐related cortices. A few patients with PPA display the neuropathological markers of Alzheimer's disease, but in an unusual distribution. The majority of the autopsies in PPA have shown either Pick's disease or lobar atrophy without distinctive histopathology. The suggestion has been made that PPA and frontal lobe dementia constitute phenotypical variations of a unitary disease process within the “Pick‐lobar atrophy” spectrum. Recent advances in chromosome 17‐linked dementias justify a rigorous search for tau polymorphisms and tauopathy in sporadic PPA. An informed approach to this syndrome will increase the effectiveness with which clinicians can address the unique challenges associated with the diagnosis and care of PPA. Ann Neurol 2001;49:425–432
Familial dyskinesia and facial myokymia (FDFM): A novel movement disorder
Authors: Fernandez Magali , Raskind Wendy , Wolff John , Matsushita Mark , Yuen Eric , Graf William , Lipe Hillary , Bird Thomas 
Published: November 2004

AbstractWe describe here familial dyskinesia and facial myokymia (FDFM), a novel autosomal dominant disorder characterized by adventitious movements that sometimes appear choreiform and that are associated with perioral and periorbital myokymia. We report a 5‐generation family with 18 affected members (10 males and 8 females) with FDFM. The disorder has an early childhood or adolescent onset. The involuntary movements are paroxysmal at early ages, increase in frequency and severity, and may become constant in the third decade. Thereafter, there is no further deterioration, and there may even be improvement in old age. The adventitious movements are worsened by anxiety but not by voluntary movement, startle, caffeine, or alcohol. The disease is socially disabling, but there is no intellectual impairment or decrease in lifespan. A candidate gene and haplotype analysis was performed in 9 affected and 3 unaffected members from 3 generations of this family using primers for polymorphic loci closely flanking or within genes of interest. We excluded linkage to 11 regions containing genes associated with chorea and myokymia: 1) the Huntington disease gene on chromosome 4p; 2) the paroxysmal dystonic choreoathetosis gene at 2q34; 3) the dentatorubral‐pallidoluysian atrophy gene at 12p13; 4) the choreoathetosis/spasticity disease locus on 1p that lies in a region containing a cluster of potassium (K+) channel genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1 gene and two other voltage‐gated K+ channel genes, KCNA5 and KCNA6; 6) the chorea‐acanthocytosis locus on 9q21; 7) the Huntington‐like syndrome on 20p; 8) the paroxysmal kinesigenic dyskinesia locus on 16p11.2‐q11.2; 9) the benign hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and 11) the chromosome 19 region that contains several ion channels and the CACNA1A gene, a brain‐specific P/Q‐type calcium channel gene associated with ataxia and hemiplegic migraine. Our results provide further evidence of genetic heterogeneity in autosomal dominant movement disorders and suggest that a novel gene underlies this new condition. Ann Neurol 2001;49:486–492
Spectroscopic studies of interaction of chlorobenzylidine with DNA
Authors: Zhong Wenying , Yu Jun‐Sheng , Huang Wenlong , Ni Kunyi , Liang Yingqiu 
Published: November 2004

AbstractElectronic absorbance and fluorescence titrations are used to probe the interaction of chlorobenzylidine with DNA. The binding of chlorobenzylidine to DNA results in hypochromism, a small shift to a longer wavelength in the absorption spectra, and emission quenching in the fluorescence spectra. These spectral characteristics suggest that chlorobenzylidine binds to DNA by an intercalative mode. This conclusion is reinforced by fluorescence polarization measurements. Scatchard plots constructed from fluorescence titration data give a binding constant of 1.3 × 105 M−1 and a binding site size of 10 base pairs. This indicates that chlorobenzylidine has a high affinity with DNA. The intercalative interaction is exothermic with a Van't Hoff enthalpy of −143 kJ/mol. This result is obtained from the temperature dependence of the binding constant. The interaction of chlorobenzylidine with DNA is affected by the pH value of the solution. The binding constant has its maximum at pH 3.0. Upon binding to DNA, the fluorescence from chlorobenzylidine is quenched efficiently by the DNA bases and the fluorescence intensity tends to be constant at high concentrations of DNA when the binding is saturated. The Stern–Volmer quenching constant obtained from the linear quenching plot is 1.6 × 104 M−1 at 25°C. The measurements of the fluorescence lifetime and the dependence of the quenching constant on the temperature indicate that the fluorescence quenching process is static. The fluorescence lifetime of chlorobenzylidine is 1.9 ± 0.4 ns. © 2001 John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 62: 315–323, 2001
Expression of GnTIII in a recombinant anti‐CD20 CHO production cell line: Expression of antibodies with altered glycoforms leads to an increase in ADCC through higher affinity for FCγRIII
Authors: Davies Julian , Jiang LiYing , Pan Li‐Zhen , LaBarre Michael J. , Anderson Darrell , Reff Mitchell 
Published: November 2004

AbstractThe gene encoding the rat glycosylation enzyme β1–4‐N‐acetylglucosaminyltransferase III (GnTIII) was cloned and coexpressed in a recombinant production Chinese hamster ovary (CHO) cell line expressing a chimeric mouse/human anti‐CD20 IgG1 antibody. The new cell lines expressed high levels of antibody and have growth kinetics similar to that of the parent. Relative QPCR showed the cell lines to express varying levels of mRNA. High‐performance liquid chromatography (HPLC) analysis showed the enzyme to have added bisecting N‐acetylglucosamine (GlcNAc) residues in most (48% to 71%) of the N‐linked oligosaccharides isolated from antibody preparations purified from the cell lines. In an ADCC assay the new antibody preparations promoted killing of CD20‐positive target cells at approximately 10‐ to 20‐fold lower concentrations than the parent. This activity was blocked using an anti‐FcγRIII antibody, supporting the role of FcγRIII binding in this increase. In addition, cell binding assays showed the modified antibody bound better to FcγRIII‐expressing cells. The increase in ADCC activity is therefore likely due to an increased affinity of the modified antibody for the FcγRIII receptor. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 288–294, 2001.
Continuous production of (R)‐phenylacetylcarbinol in an enzyme‐membrane reactor using a potent mutant of pyruvate decarboxylase from Zymomonas mobilis
Authors: Goetz Günter , Iwan Peter , Hauer Bernhard , Breuer Michael , Pohl Martina 
Published: November 2004

AbstractThe optimization of a continuous enzymatic reaction yielding (R)‐phenylacetylcarbinol (PAC), an intermediate of the L‐ephedrine synthesis, is presented. We compare the suitability of three pyruvate decarboxylases (PDC), PDC from Saccharomyces cerevisiae, PDC from Zymomonas mobilis, and a potent mutant of the latter, PDCW392M, with respect to their application in the biotransformation using acetaldehyde and benzaldehyde as substrates. Among these, the mutant enzyme was the most active and most stable one. The reaction conditions of the carboligation reaction were investigated by determining initial rate velocities with varying substrate concentrations of both aldehydes. From the resulting data a kinetic model was inferred which fits the experimental data with sufficient reliability to deduce the optimal concentrations of both substrates for the enzymatic process. The results demonstrate that the carboligation is most efficiently performed using a continuous reaction system and feeding both aldehydes in equimolar concentration. Initial studies using a continuously operated enzyme‐membrane reactor gave (R)‐PAC with a space–time yield of 81 g L‐1 · d‐1 using a substrate concentration of 50 mM of both aldehydes. The yield was easily increased by cascadation of enzyme‐membrane reactors. The new strategy allows the synthesis of (R)‐PAC from cheap substrates in an aqueous reaction system. It thereby overcomes the limitation of by‐product formation that severely limits the current fermentative process. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 317–325, 2001.