bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal molecular mimicry in immune‐mediated neurologic disease
Authors: Levin Michael C. , Krichavsky Marc , Berk Jeff , Foley Shanon , Rosenfeld Myrna , Dalmau Josep , Chang Greg , Posner Jerome B. , Jacobson Steven 
Published: January 2005

AbstractMolecular mimicry is implicated in the pathogenesis of autoimmune diseases such as diabetes mellitus, rheumatoid arthritis, and multiple sclerosis (MS). Cellular and antibody‐mediated immune responses to shared viral‐host antigens have been associated with the development of disease in these patients. Patients infected with human T‐lymphotropic virus type I (HTLV‐I) develop HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), an immunemediated disorder of the central nervous system (CNS) that resembles some forms of MS. Damage to neuronal processes in the CNS of HAM/TSP patients is associated with an activated cellular and antibody‐mediated immune response. In this study, IgG isolated from HAM/TSP patients was immunoreactive with uninfected neurons and this reactivity was HTLV‐I specific. HAM/TSP IgG stained uninfected neurons in human CNS and cell lines but not nonneuronal cells. Neuronal western blots showed IgG reactivity with a single 33‐kd band in all HAM/TSP patients tested. By contrast, no neuron‐specific IgG reactivity could be demonstrated from HTLV‐I seronegative controls and, more important, from HTLV‐I seropositive, neurologically asymptomatic individuals. Both immunocytochemical staining and western blot reactivity were abolished by preincubating HAM/TSP IgG with HTLV‐I protein lysate but not by control proteins. Staining of CNS tissue by a monoclonal antibody to HTLV‐I tax (an immunodominant HTLV‐I antigen) mimicked HAM/TSP IgG immunoreactivity. There was no staining by control antibodies. Absorption of HAM/TSP IgG with recombinant HTLV‐I tax protein or preincubation of CNS tissue with the monoclonal antibody to HTLV‐I tax abrogated the immunocytochemical and western blot reactivity of HAM/TSP IgG. Furthermore, in situ human IgG localized to neurons in HAM/TSP brain but not in normal brain. These data indicate that HAM/TSP patients develop an antibody response that targets uninfected neurons, yet reactivity is blocked by HTLV‐I, suggesting viral‐specific autoimmune reactivity to the CNS, the damaged target organ in HAM/TSP.
Interictal cortical excitability in migraine: A study using transcranial magnetic stimulation of motor and visual cortices
Authors: Áfra Judit , Mascia Addolorata , Phy Pascale Gérard , de Noordhout Alain Maertens , Schoenen Jean 
Published: January 2005

AbstractWe performed transcranial magnetic stimulations of the motor and visual cortices in healthy controls (n = 27) and in patients suffering from migraine without (n = 33) or with (n = 25) aura between attacks. By using a 13‐cm circular coil placed over the vertex and recordings of the first dorsal interosseus muscle, we measured thresholds (at rest and during contraction), amplitudes of motor evoked potentials and cortical silent periods. Paired stimulations with short (1–20 msec) interstimulus intervals were performed to assess intracortical inhibition. The visual cortex was stimulated with the same coil placed over the occipital scalp (7 cm above the inion) and the prevalence and threshold of phosphene production was determined. In patients with migraine with aura, motor thresholds during isometric contraction were significantly higher, whereas the prevalence of stimulation‐induced phosphene production was lower compared with healthy controls. These changes were not correlated with attack frequency or disease duration. No differences were found between subject groups in thresholds at rest, motor evoked potential amplitudes, cortical silent periods, or response curves after paired stimuli. These results are in favor of cortical hypoexcitability rather than hyperexcitability in patients with migraine with aura between attacks.
Distinct pH homeostatic features in lymphoblasts from Alzheimer's disease patients
Authors: Ibarreta Dolores , Urcelay Elena , Parrilla Roberto , Ayuso Matilde S. 
Published: January 2005

AbstractEpstein‐Barr–transformed lymphocytes from Alzheimer's disease patients showed the following distinct features in controlling the intracellular pH compared with cells from normal age‐matched controls: (1)The αIgM‐induced intracellular acidification was more pronounced in Alzheimer's disease than control cells and this effect appears to be associated with a loss of effectiveness of a Ca2+/ calmodulin‐dependent mechanism in controlling the activity of the Na+/H+ exchanger; and (2) the intracellular H+‐buffering capacity and the rate of proton efflux in response to an acid load were both decreased in Alzheimer's disease cells. It is concluded that the amplitude of the intracellular pH changes under acidloading conditions will always be greater in Alzheimer's disease than in control cells.
Deficient transport of dehydroascorbic acid in the glucose transporter protein syndrome
Authors: Klepper Jörg , Vera Juan Carlos , de Vivo Darryl C. 
Published: January 2005

AbstractThe glucose transporter protein syndrome (GTPS) is caused by defective transport of glucose across the blood–brain barrier via the glucose transporter GLUT1, resulting in hypoglycorrhachia, infantile seizures, and developmental delay. Recent reports indicated that GLUT1 is a multifunctional transporter. We investigated the transport of vitamin C in its oxidized form (dehydroascorbic acid) via GLUT1 into erythrocytes of 2 patients with GTPS. In both patients, uptake of oxidized vitamin C was 61% of the mothers' values. Our findings are consistent with recent observations that vitamin C is transported in its oxidized form via GLUT1. We speculate that impaired transport of this substrate and perhaps other substrates in GTPS might contribute to the pathophysiology of this condition.
Genetic association of two chromosome 14 genes (presenilin 1 and α1‐Antichymotrypsin) with Alzheimer's disease
Authors: Wang Xiaoyan , DeKosky Steven T. , Wisniewski Stephen , Aston Christopher E. , Kamboh M. Ilyas 
Published: January 2005

AbstractWe have investigated the association of two candidate genes on chromosome 14, presenilin 1 (PS1) and α1‐antichymotrypsin (ACT), with the risk of sporadic Alzheimer's disease (AD) by using 427 AD cases and 250 controls. The frequency of the ACT*A allele was significantly higher in cases than controls (0.550 vs 0.466). The stratification of the ACT data by PS1 genotypes showed that the risk associated with the ACT*A allele was confined to PS1*1 carriers only. The two‐site haplotype data for PS1 and ACT showed that the A1 haplotype, carrying the ACT*A and PS1*1 alleles, was more frequent in cases then controls (0.310 vs 0.251), whereas the frequency of the T2 haplotype, carrying the ACT*T and PS1*2 alleles, was lower in cases than controls (0.177 vs 0.237). These data indicate a possible synergistic effect of these two loci on the risk of AD.
Matrix metalloproteinases contribute to the blood—brain barrier disruption during bacterial meningitis
Authors: Paul Robert , Lorenzl Stefan , Koedel Uwe , Sporer Bernd , Vogel Ulrich , Frosch Matthias , Pfister Hans‐Walter 
Published: January 2005

AbstractIn this study, we investigated the involvement of matrix metalloproteinases (MMPs) in the pathophysiology of bacterial meningitis. By using an enzyme immunoassay, high concentrations of MMP‐9 were detected in the cerebrospinal fluid (CSF) of adult patients with bacterial meningitis but not in controls, and in patients with Guilain‐Barré syndrome. Moreover, we observed significantly elevated concentrations of the tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in the CSF of patients with bacterial meningitis, compared with controls. In a rat model of meningococcal meningitis, intracisternal injection of heat‐killed meningococci caused a disruption of the blood–;brain barrier (BBB), and increase in intracranial pressure, and CSF pleocytosis paralleled by the occurrence of MMP‐9 activity in the CSF 6 hours after meningococcal challenge. The MMP inhibitor batimastat (BB‐94) significantly reduced the BBB disruption and the increase in intracranial pressure irrespective of the time of batmastat administration (15 minutes before and 3 hours after meningococcal challenge) but failed to significantly reduce CSF white blood cell counts. In conclusion, our results suggest that MMPs are involved in the alterations of BBB permeability during experimental meningococcal meningitis.
Dopa‐responsive dystonia: A clinical and molecular genetic study
Authors: Bandmann O. , Valente E. M. , Holmans P. , Surtees R. A. H. , Walters J. H. , Wevers R. A. , Marsden C. D. , Wood N. W. 
Published: January 2005

AbstractWe have studied the GTP‐cyclohydrolase 1 (GCH‐1) gene in 30 patients with the diagnosis of clinically definite (n = 20) or possible (n = 10) dopa‐responsive dystonia (DRD) as well as in a child with atypical phenylketonuria due to complete GCH‐1 deficiency. A large number of new heterozygote mutations (seven point mutations, two splice site mutations and one deletion) as well as a new homozygote mutations in the child with atypical phenylketonuria were detecte. In addition, two previously described mutations wer found in two other cases. We further extended our investigation of GCH‐1 to the 5′ and 3′ regulatory regions and report the first detection of point mutations in the 5′ untranslated region. Demethylation of CpG islands does not appear to be an important causative factor for the GCH‐1 mutations in DRD. In addition, we have extended the clinical phenotype of genetically proven DRD to focal dystonia, dystonia with relapsing and remitting course, and DRD with onset in the first week of life. None of our DRD patients without a mutation in GCH‐1 had the 3‐bp deletion recently detected in DYT1, the causative gene for idiopathic torsion dystonia with linkage to 9q34.
Mechanism of selective motor neuronal death after exposure of spinal cord to glutamate: Involvement of glutamate‐induced nitric oxide in motor neuron toxicity and nonmotor neuron protection
Authors: Urushitani Makoto , Shimohama Shun , Kihara Takeshi , Sawada Hideyuki , Akaike Akinori , Ibi Masakazu , Inoue Ryotaku , Kitamura Yoshihisa , Taniguchi Takashi , Kimura Jun 
Published: January 2005

AbstractIn this study, we analyzed the mechanism of selective motor neuronal death, a characteristic of amyotrophic lateral sclerosis, using embryonic rat spinal cord culture. When dissociated cultures were exposed to low‐level glutamate (Glu) coadministered with the Glu transporter inhibitor L‐trans‐pyrrolidine‐2,4‐decarboxylate (PDC) for 24 hours, motor neurons were selectively injured through N‐methyl‐D‐asparate (NMDA) and α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)/kainate receptors. Nitric oxide synthase (NOS) inhibitors attenuated this toxicity, and long‐acting nitric oxide (NO) donors damaged motor neurons selectively. Nonmotor neurons survived after exposure to low‐dose Glu/PDC, but Glu‐induced toxicity was potentiated by coadministration of an NO‐dependent guanylyl cyclase inhibitor. In addition, 8‐bromo‐cyclic GMP, a soluble cyclic GMP analogue, rescued nonmotor neurons, but not motor neurons, exposed to high‐dose Glu/PDC. Twenty‐four hours' incubation with PDC elevated the number of neuronal NOS‐immunoreactive neurons by about twofold compared with controls, and a double‐staining, study, using the motor neuron marker SMI32, revealed that most of them were nonmotor neurons. These findings suggest that selective motor neuronal death caused by chornic low‐level exposure to Glu is mediated by the formation of NO in nonmotor neurons, which inversely protects nonmotor neurons through the guanylyl cyclase‐cyclic GMP casade. Induction of neuronal NOS in nonmotor neurons might enhance both the toxicity of motor neurons and the protection of nonmotor neurons, which could explain the pathology of amyotrophic lateral sclerosis.
Matrilineal inheritance of complex I dysfunction in a multigenerational Parkinson's disease family
Authors: Swerdlow Russell H. , Parks Janice K. , Davis John N. , Cassarino David S. , Trimmer Patricia A. , Currie Lillian J. , Dougherty John , Bridges W. Scott , Bennett James P. , Wooten G. Frederick , Parker W. Davis 
Published: January 2005

AbstractRecent data suggesting complex I dysfunction in Parkinson's disease (PD) arises from mitochondrial DNA (mtDNA) mutation does not conclusively answer whether the responsible genetic lesion is inherited (primary) or somatic (secondary). To address this question, we identified a family in which multiple members over three generations are affected with PD through exclusively maternal lines. Cytoplasmic hybrids (cybrids) were created for 15 family members over two generations by trnsferring each individual's mtDNA to mtDNA‐depleted human neuroblastoma cells. Eight of the 15 cybrid lines contained mtDNA obtained from maternally descended family members and seven contained mtDNA from paternally descended family members. After 6 weeks of culture, cybrid cell lines were assayed for complex I activity and oxidative stress, and mitochondrial morphology was analyzed by electron microscopy. Compared with the cybrid lines containing mtDNA from paternal descendants, cybrid lines containing mtDNA from maternal descendants had lower complex I activity, increased reactive oxygen species production, increased radical scavenging enzyme activities, and more abnormal mitochondrial morphologic features. These findings were present in cybrid lines containing mtDNA from maternal descendants with PD as well as in currently asymptomatic young maternal descendants, and support a precedent for inherited mtDNA mutation in some persons with PD.
Remodeling of neuronal circuitries in human temporal lobe epilepsy: Increased expression of highly polysialylated neural cell adhesion molecule in the hippocampus and the entorhinal cortex
Authors: Mikkonen Mia , Soininen Hilkka , Kälviäinen Reetta , Tapiola Tero , Ylinen Aarne , Vapalahti Matti , Paljärvi Leo , Pitkänen Asla 
Published: January 2005

AbstractNeuronal loss and axonal sprouting are the most typical histopathological findings in the hippocampus of patients with drug‐refractory temporal lobe epilepsy (TLE). It is under dispute, however, whether remodeling of neuronal circuits is a continuous process or whether it occurs only during epileptogenesis. Also, little is known about the plasticity outside of the hippocampus. We investigated the immunoreactivity of the highly polysialylated neural cell adhesion molecule (PSA‐NCAM) in the surgically removed hippocampus and the entorhinal cortex of patients with drug‐refractory TLE (n = 25) and autopsy controls (n = 7). Previous studies have shown that the expression of PSA‐NCAM is associated with the induction of synaptic plasticity, neurite outgrowth, neuronal migration, and events requiring remodeling or repair of tissue. In patients with TLE, the optical density (OD) of punctate PSA‐NCAM immunoreactivity was increased both in the inner and outer molecular layers of the dentate gyrus, compared with controls. The intensity of PSA‐NCAM immunoreactivity in the inner molecular layer correlated with the duration of epilepsy, severity of hippocampal neuronal loss, density of mossy fiber sprouting, and astrogliosis. In TLE patients with only mild neuronal loss in the hippocampus, the density of infragranular immunopositive neurons was increased twofold compared with controls, whereas in TLE patients with severe neuronal loss, the infragranular PSA‐NCAM–positive cells were not present. In the hilus, the somata and tortuous dendrites of some surviving neurons were intensely stained in TLE. PSA‐NCAM immunoreactivity was also increased in CA1 and in layer II of the rostral entorhinal cortex, where immunopositive neurons were surrounded by PSA‐NCAM‐positive fibers and puncta. Our data provide evidence that synaptic reorganization is an active process in human drug‐refractory TLE. Moreover, remodeling is not limited to the dentate gyrus, but also occurs in the CA1 subfield and the entorhinal cortex.
Reduction in HTLV‐I proviral load and spontaneous lymphoproliferation in HTLV‐I–associated myelopathy/tropical spastic paraparesis patients treated with humanized anti‐tac
Authors: Lehky Tanya J. , Levin Michael C. , Kubota Ryuji , Bamford Richard N. , Flerlage Alfred N. , Soldan Samantha S. , Leist Thomas P. , Xavier Andrew , White Jeffrey D. , Brown Margaret , Fleisher Thomas A. , Top Lois E. , Light Susan , McFarland Henry F. , Waldmann Thomas A. , Jacobson Steven 
Published: January 2005

AbstractHuman T‐lymphotropic virus type I (HTLV‐I)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disease that results from an interaction of retroviral infection and immune activation. In this study, five doses (1 mg/kg) of humanized anti‐Tac antibody were administered to 9 HAM/TSP patients at weeks 0,2,6,10, and 14. Preliminary immunological studies on HAM/TSP patients treated with humanized anti‐Tac indicate that there is a selective down‐regulation of activated T cells and a decrease in the HTLV‐I viral load in peripheral blood lymphocytes, most likely through the selective removal of HTLV‐I–infected, activated CD4+ lymphocytes.
Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis
Authors: Sadatipour B. Tayyebeh , Greer Judith M. , Pender Michael P. 
Published: January 2005

AbstractPlasma samples from 70 patients with multiple sclerosis (MS), 41 patients with other neurological diseases (OND), and 38 healthy subjects were examined for antibodies against gangliosides GM1, GM3, GD1a, GD1b, and GD3 using enzyme‐linked immunosorbent assays. The percentages of subjects with increased anti‐GM3 responses were significantly higher in the primary progressive MS (56.3%) and secondary progressive MS (42.9%) groups than in the relapsing‐remitting MS (2.9%), healthy subject (2.6%), and OND (14.6%) groups. Elevated antiganglioside antibodies may be secondary to axonal damage or may be a cause of axonal damage and accumulating disability in progressive MS. In either case, they may serve as a marker of axonal damage in MS.
Conformational aspects of polypeptides. XVIII. Conformational studies of oligopeptides derived from L‐alanine
Authors: Goodman Murray , Langsam Michael , Rosen Ira G. 
Published: December 2004

AbstractThe conformations of oligopeptides derived from L‐alanine and co‐oligomers of L‐alanine with γ‐methyl‐L‐glutamate were studied in several solvents via optical rotation and far‐ultraviolet spectroscopy. Calculated values for optical rotation based on model compounds were compared with experimental values for the oligomers. In trifluoroacetic and dichloroacetic acids, the oligomers and co‐oligomers exhibit rotations in close agreement with predicted values based on model compounds. Thus, in these solvents only nonhelical conformations exist. In trifluoroethanol, the experimental points of molar rotation for the pentamer and larger oligomers no longer follow the predicted values. In addition, the benzyloxycarbonyl and acetyl cononamers show b0 values of about −150, which demonstrates the presence of stable helical forms for these peptides. We also examined the molar extinction coefficients of oligopeptides in the 190 mμ region and determined the values for nonhelical peptide groups. The molar extinction coefficients per amide bond for the benzyloxycarbonyl and acetyl cononamers show extensive hypo‐chromism, once again indicating the presence of stable helices for these compounds in trifluoroethanol.
Asymmetric selection in the copolymerization of N‐carboxy‐L‐ and D‐alanine anhydride
Authors: Tsuruta Teiji , Inoue Shohei , Matsuura Kazuo 
Published: December 2004

AbstractThe copolymerization of N‐carboxy‐L‐ and D‐alanine anhydride with methanol as initiator was carried out. The enantiomer excess in the starting monomer mixture is preferentially incorporated into polymer chains, demonstrating asymmetric selection during the D‐ and L‐copolymerization. The mechanism of asymmetric‐selective polymerization of α‐amino acid NCA is discussed in terms of the stereoregulation by molecular asymmetry of the growing polymer chain.
Far‐infrared spectra of N‐methylacetamide and related compounds and hydrogen‐bond force constants
Authors: Itoh Koichi , Shimanouchi Takehiko 
Published: December 2004

AbstractFar‐infrared spectra of N‐methylacetamide and other monosubstituted amides were measured in the liquid state in the region from 250 to 60 cm.−1. Bands characteristic of the molecules with a peptide bond were found and assigned to the hydrogen‐bond vibration and the CN torsional vibration. Far‐infrared and Raman spectra of crystalline N‐methylacetamide were measured. The normal coordinate treatment for the low‐temperature modification of cystalline N‐methylacetamide was made. A reasonable set of force constants can explain all the spectra and their change due to the modification transition.
Circular dichroism of polynucleotides: A general method applied to dimers
Authors: Johnson W. C. , Tinoco I. 
Published: December 2004

AbstractA method is described which relates the circular dichroism of a polymer to its conformation. The method takes into account near and accidental degeneracies and eliminates the artificial distinction between degenerate and nondegenerate systems. Comparison of this method with perturbation theory indicates that the errors inherent in nondegenerate perturbation theory tend to cancel when a circular dichroism spectrum is calculated. The method is applied to dinucleoside phosphates.
Une Méthode de Dosage des Isomères de Rotation des Dipeptides en Solution par Spectroscopie infrarouge
Authors: Avignon Michel , Van Huong Pham 
Published: December 2004

AbstractAn infrared spectroscopic method of quantitative analysis of dipeptides CH3CONHCHR1CONHR2 in solution is proposed. The application of the method to a series of dipeptides with different side chains shows that the amount of the “bent form” tends to become important when the side chain is large.
Conformation of poly‐L‐tyrosine in aqueous solution
Authors: Patrone Eligio , Conio Giuseppina , Brighetti Sergio 
Published: December 2004

AbstractThe conformational transition of poly‐L‐tyrosine in 0.1M KCl was investigated by ORD and infrared spectroscopy, potentiometric titration, and sedimentation velocity experiments. It is shown that the fully ordered conformer is obtained by slow titration of the random coil with 0.1N HCl at 25°C. The charge‐induced transition, at variance with other poly‐α‐amino acids, is completed in a narrow range of α. An aggregation process was detected both by potentiometric titration and sedimentation velocity. The polyamino acid aggregates around α = 0.7 at 25°C when the conformational transition is almost complete. Infrared spectra, in the region of the amide I band (1650 cm−1) showed that the transition is a random coil → antiparallel β one. Evidence exists that the form is of the intramolecular type. The foregoing interpretations of ORD and CD spectra in terms of the α‐helix conformation are discussed.
The temperature‐dependent swelling of elastin
Authors: Gosline John M. 
Published: December 2004

AbstractIt is suggested that the temperature‐dependent swelling behavior of water‐swollen elastin is due entirely to the interaction of the numerous nonpolar groups in the elastin protein wiht the aqueous swelling solvent (i.e., ahydrophobic interaction). Flory‐Rehner theory for network swelling was used to test this hypothesis. Calculated values for the solvent–polymer interaction parameter, χ1, derived from swelling data indicate that water is a very poor solvent for elastin at all temperatures over the range 0–70° C. Comparison of the calculated χ1 values with theoretical values for the free energy of interaction of nonpolar solutes and water strongly suggests that the swelling behavior of elastin can be attributed quantitatively to hydrophobic interactions. The implications of these results for the structure and elastic mechanism of elastin are discussed.