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1.
PLoS Negl Trop Dis ; 14(7): e0008361, 2020 07.
Article in English | MEDLINE | ID: mdl-32667912

ABSTRACT

Human T-cell leukemia virus type 1 (HTLV-1) causes incurable adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have increased levels of HTLV-1-infected cells compared with asymptomatic HTLV-1 carriers. However, the roles of cellular genes in HTLV-1-infected CD4+ T cells await discovery. We performed microarray analysis of CD4+ T cells from HAM/TSP patients and found that the ABL1 is an important gene in HAM/TSP. ABL1 is a known survival factor for T- and B-lymphocytes and is part of the fused gene (BCR-ABL) known to be responsible for chronic myelogenous leukemia (CML). ABL1 tyrosine kinase inhibitors (TKIs), including imatinib, nilotinib, and dasatinib, are used clinically for treating CML. To evaluate whether ABL1 is indeed important for HAM/TSP, we investigated the effect of TKIs on HTLV-1-infected cells. We developed a propidium monoazide-HTLV-1 viability quantitative PCR assay, which distinguishes DNA from live cells and dead cells. Using this method, we were able to measure the HTLV-1 proviral load (PVL) in live cells alone when peripheral blood mononuclear cells (PBMCs) from HAM/TSP cases were treated with TKIs. Treating the PBMCs with nilotinib or dasatinib induced significant reductions in PVL (21.0% and 17.5%, respectively) in live cells. Furthermore, ABL1 siRNA transfection reduced cell viability in HTLV-1-infected cell lines, but not in uninfected cell lines. A retrospective survey based on our clinical records found a rare case of HAM/TSP who also suffered from CML. The patient showed an 84.2% PVL reduction after CML treatment with imatinib. We conclude that inhibiting the ABL1 tyrosine kinase specifically reduced the PVL in PBMCs from patients with HAM/TSP, suggesting that ABL1 is an important gene for the survival of HTLV-1-infected cells and that TKIs may be potential therapeutic agents for HAM/TSP.


Subject(s)
HTLV-I Infections/complications , Human T-lymphotropic virus 1/physiology , Leukocytes, Mononuclear/virology , Paraparesis, Tropical Spastic/enzymology , Spinal Cord Diseases/enzymology , Adult , Aged , DNA, Viral/genetics , Female , HTLV-I Infections/virology , Humans , Male , Middle Aged , Paraparesis, Tropical Spastic/drug therapy , Paraparesis, Tropical Spastic/etiology , Paraparesis, Tropical Spastic/genetics , Protein Kinase Inhibitors/administration & dosage , Proto-Oncogene Proteins c-abl/antagonists & inhibitors , Proto-Oncogene Proteins c-abl/genetics , Proto-Oncogene Proteins c-abl/metabolism , Proviruses/genetics , Proviruses/physiology , Retrospective Studies , Spinal Cord Diseases/drug therapy , Spinal Cord Diseases/etiology , Spinal Cord Diseases/genetics , Viral Load
2.
Oxid Med Cell Longev ; 2020: 4909103, 2020.
Article in English | MEDLINE | ID: mdl-31998438

ABSTRACT

Direct peritoneal resuscitation with pyruvate (Pyr-PDS) has emerged as an interesting candidate to alleviate injury in diverse organs, while the potential mechanism has yet to be fully elucidated. To explore the effect of autophagy in the spinal cord ischemia-reperfusion (SCIR) injury and the underlying mechanism, we established a model of SCIR in vivo and in vitro. In vivo, male SD rats underwent aortic occlusion for 60 min and then followed by intraperitoneally infused with 20 mL of pyruvate or normal saline for 30 min, and the spinal cords were removed for analysis after 48 h of reperfusion. The functional and morphological results showed that Pyr-PDS alleviated SCIR injury; meanwhile, the expression of autophagy-related genes and transmission electron microscopy displayed autophagy was activated by SCIR injury, and Pyr-PDS treatment could further upregulate the degree of autophagy which plays a protective part in the SCIR injury, while there is no significant difference after treatment with saline. In addition, SCIR injury inhibited expression of PHD2, which results to activate its downstream HIF-1α/BNIP3 pathway to promote autophagy. In the Pyr-PDS, the results revealed PHD2 was further inhibited compared to the SCIR group, which could further activate the HIF-1α/BNIP3 signaling pathway. Additionally, oxygen-glucose deprivation and reoxygenation were applied to SH-SY5Y cells to mimic anoxic conditions in vitro, and the expression of autophagy-related genes, PHD2, and its downstream HIF-1α/BNIP3 pathway showed the same trend as the results in vivo. Besides, IOX2, a specific inhibitor of PHD2 was also treated to SH-SY5Y cells during reoxygenation, in which the result is as same as the pyruvate group. Then, we observed the expression of autophagy-related genes and the HIF-1α signal pathway in the process of reoxygenation; the results showed that as the reoxygenation goes, the expression of the HIF-1α signal pathway and degree of autophagy came to decrease gradually, while treated with pyruvate could maintain autophagy high and stable through keeping PHD2 at a lower level during reoxygenation, and the latter was observed downregulated during reoxygenation process from 0 to 24 hours in a time-effect way. The above results indicated that direct peritoneal resuscitation with pyruvate showed effective protection to ischemia-reperfusion of the spinal cord through activating autophagy via acting on PHD2 and its downstream HIF-1α/BNIP3 pathway.


Subject(s)
Autophagic Cell Death/drug effects , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Pyruvic Acid/pharmacology , Reperfusion Injury , Signal Transduction/drug effects , Spinal Cord Diseases , Animals , Disease Models, Animal , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Injections, Intraperitoneal , Membrane Proteins/metabolism , Mitochondrial Proteins/metabolism , Rats , Reperfusion Injury/enzymology , Reperfusion Injury/pathology , Reperfusion Injury/prevention & control , Resuscitation , Spinal Cord Diseases/enzymology , Spinal Cord Diseases/pathology , Spinal Cord Diseases/prevention & control
3.
J Vet Med Sci ; 79(2): 375-379, 2017 Feb 28.
Article in English | MEDLINE | ID: mdl-27941298

ABSTRACT

Canine degenerative myelopathy (DM) is an adult-onset, progressive neurodegenerative disease that occurs in multiple dog breeds. A DM-associated mutation of the canine superoxide dismutase 1 (SOD1) gene, designated as c.118G>A (p.E40K), has been implicated as one of pathogenetic determinants of the disease in many breeds, but it remains to be determined whether the c.118G>A mutation is responsible for development or progression of DM in Collies. Previously, a Rough Collie was diagnosed clinically and histopathologically as having DM in Japan, suggesting the possibility that the Collie breed may be predisposed to DM due to the high frequency of c.118G>A in Japan. In this study, accumulation and aggregate formation of SOD1 protein were retrospectively demonstrated in the spinal cord of the DM-affected dog by immunohistochemical analysis. Furthermore, a molecular epidemiological survey revealed a high carrier rate (27.6%) and mutant allele frequency (0.138) of c.118G>A in a population of Collies in Japan, suggesting that the Collie breed may be predisposed to DM associated with c.118G>A, and the prevention of DM in Collies in Japan should be addressed through epidemiological and genetic testing strategies.


Subject(s)
Dog Diseases/genetics , Neurodegenerative Diseases/veterinary , Spinal Cord Diseases/veterinary , Superoxide Dismutase-1/genetics , Animals , Dog Diseases/enzymology , Dog Diseases/pathology , Dogs , Genetic Predisposition to Disease , Immunohistochemistry/veterinary , Japan , Male , Neurodegenerative Diseases/enzymology , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/pathology , Point Mutation , Retrospective Studies , Species Specificity , Spinal Cord Diseases/enzymology , Spinal Cord Diseases/genetics , Spinal Cord Diseases/pathology
4.
J Neurol Sci ; 318(1-2): 55-64, 2012 Jul 15.
Article in English | MEDLINE | ID: mdl-22542607

ABSTRACT

Canine degenerative myelopathy (DM) is an adult-onset, fatal neurodegenerative disease with many similarities to an upper-motor-neuron-onset form of human amyotrophic lateral sclerosis (ALS), that results from mutations in the superoxide dismutase (SOD1) gene. DM occurs in many dog breeds, including the Pembroke Welsh Corgi and Boxer. The initial upper motor neuron degeneration produces spastic paraparesis and affected dogs develop general proprioceptive ataxia in the pelvic limbs. Dog owners usually elect euthanasia when their dog becomes paraplegic. When euthanasia is delayed, lower motor neuron signs including ascending tetraparesis, flaccid paralysis and widespread muscle atrophy emerge. For this study, muscle and peripheral nerve specimens were evaluated at varying disease stages from DM-affected Pembroke Welsh Corgis and Boxers that were homozygous for the SOD1 mutation and had spinal cord histopathology consistent with DM. Comparisons were made with age- and breed-matched control dogs. Here we provide evidence that Pembroke Welsh Corgis and Boxers with chronic DM develop muscle atrophy consistent with denervation, peripheral nerve pathology consistent with an axonopathy, and to a lesser degree demyelination. Canine DM has been proposed as a potential spontaneous animal disease model of human ALS. The results of this study provide further support that canine DM recapitulates one form of the corresponding human disorder and should serve as a valuable animal model to develop therapeutic strategies.


Subject(s)
Disease Progression , Dog Diseases/genetics , Heredodegenerative Disorders, Nervous System/genetics , Mutation, Missense/genetics , Peripheral Nervous System Diseases/genetics , Spinal Cord Diseases/genetics , Superoxide Dismutase/genetics , Animals , Disease Models, Animal , Dog Diseases/enzymology , Dogs , Genetic Predisposition to Disease/genetics , Heredodegenerative Disorders, Nervous System/enzymology , Heredodegenerative Disorders, Nervous System/pathology , Homozygote , Peripheral Nervous System Diseases/enzymology , Peripheral Nervous System Diseases/pathology , Spinal Cord Diseases/enzymology , Spinal Cord Diseases/pathology , Superoxide Dismutase/deficiency , Superoxide Dismutase-1
5.
Cell Mol Neurobiol ; 30(1): 123-35, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19693665

ABSTRACT

In the Wobbler mouse, a mutation in the Vps54 gene is accompanied by motoneuron degeneration and astrogliosis in the cervical spinal cord. Previous work has shown that these abnormalities are greatly attenuated by progesterone treatment of clinically afflicted Wobblers. However, whether progesterone is effective at all disease stages has not yet been tested. The present work used genotyped (wr/wr) Wobbler mice at three periods of the disease: early progressive (1-2 months), established (5-8 months) or late stages (12 months) and age-matched wildtype controls (NFR/NFR), half of which were implanted with a progesterone pellet (20 mg) for 18 days. In untreated Wobblers, degenerating vacuolated motoneurons were initially abundant, experienced a slight reduction at the established stage and dramatically diminished during the late period. In motoneurons, the cholinergic marker choline acetyltransferase (ChAT) was reduced at all stages of the Wobbler disease, whereas hyperexpression of the growth-associated protein (GAP43) mRNA preferentially occurred at the early progressive and established stages. Progesterone therapy significantly reduced motoneuron vacuolation, enhanced ChAT immunoreactive perikarya and reduced the hyperexpression of GAP43 during the early progressive and established stages. At all stage periods, untreated Wobblers showed high density of glial fibrillary acidic protein (GFAP)+ astrocytes and decreased number of glutamine synthase (GS) immunostained cells. Progesterone treatment down-regulated GFAP+ astrocytes and up-regulated GS+ cell number. These data reinforced the usefulness of progesterone to improve motoneuron and glial cell abnormalities of Wobbler mice and further showed that therapeutic benefit seems more effective at the early progressive and established periods, rather than on advance stages of spinal cord neurodegeneration.


Subject(s)
Motor Neurons/drug effects , Motor Neurons/pathology , Neuroglia/drug effects , Neuroglia/pathology , Progesterone/pharmacology , Spinal Cord Diseases/pathology , Spinal Cord/pathology , Animals , Anterior Horn Cells/drug effects , Anterior Horn Cells/enzymology , Anterior Horn Cells/pathology , Astrocytes/drug effects , Astrocytes/metabolism , Astrocytes/pathology , Cell Count , Choline O-Acetyltransferase/metabolism , Disease Models, Animal , Female , GAP-43 Protein/genetics , GAP-43 Protein/metabolism , Gene Expression Regulation/drug effects , Genotype , Glial Fibrillary Acidic Protein/metabolism , Glutamate-Ammonia Ligase/metabolism , Image Processing, Computer-Assisted , Male , Mice , Mice, Neurologic Mutants , Motor Neurons/enzymology , Neuroglia/enzymology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Spinal Cord/drug effects , Spinal Cord/metabolism , Spinal Cord Diseases/enzymology
6.
Thyroid ; 19(12): 1401-6, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19916870

ABSTRACT

BACKGROUND: We have shown substantial expression of type 3 deiodinase (D3, a major enzyme involved in the inactivation of thyroid hormone) in infiltrating leukocytes in several models of inflammation. Recently, thyroid hormone has been shown to improve remyelination in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. As induction of D3 may play an important role in decreasing local bioavailability of thyroid hormone at inflammation sites, we hypothesized that D3 is induced in spinal cord inflammatory lesions in EAE. METHODS: The aim of the study was to evaluate D3 expression in spinal cord inflammatory lesions of EAE Dark Agouti rats and to investigate D3 induction in activated monocytes. RESULTS: Here, we show marked expression of D3 by granulocytes and macrophages in spinal cord inflammatory lesions of EAE rats. We further confirm induction of D3 expression in vitro in monocytes that were activated toward proinflammatory or immunomodulatory phenotypes. CONCLUSIONS: We observed increased D3 expression both in spinal cord inflammatory lesions during EAE and in activated monocytes. Although increased D3 expression theoretically results in decreased triiodothyronine availability, it is unknown at present whether reduced local triiodothyronine concentrations are involved in impaired remyelination as observed during EAE.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/enzymology , Iodide Peroxidase/biosynthesis , Spinal Cord Diseases/enzymology , Animals , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Leukocytes/enzymology , Rats , Spinal Cord Diseases/pathology
7.
J Child Neurol ; 23(9): 1043-8, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18645204

ABSTRACT

Biotinidase deficiency is an autosomal recessively inherited disorder that manifests during childhood with various cutaneous and neurological symptoms particularly seizures, hypotonia, and developmental delay. Spinal cord disease has been reported rarely. We describe a 3-year-old boy with profound biotinidase deficiency who presented with progressive spastic paraparesis and ascending weakness in the absence of the usual characteristic neurological manifestations. Supplementation with biotin resulted in resolution of paraparesis with persistent mild spasticity in the lower limbs. DNA mutation analysis revealed that he was homozygous for a novel missense mutation (C>T1339;H447Y) in the BTD gene. This case indicates that biotinidase deficiency should be included in the differential diagnosis of subacute myelopathy and emphasizes the importance of a prompt diagnosis to prevent irreversible neurological damage.


Subject(s)
Biotin/metabolism , Biotinidase Deficiency/complications , Biotinidase Deficiency/genetics , Genetic Predisposition to Disease/genetics , Spinal Cord Diseases/enzymology , Spinal Cord Diseases/genetics , Biotin/administration & dosage , Biotinidase Deficiency/physiopathology , Child, Preschool , DNA Mutational Analysis , Early Diagnosis , Gene Expression Regulation, Enzymologic/genetics , Genetic Markers/genetics , Genetic Testing , Genotype , Humans , Male , Mutation, Missense/genetics , Paraparesis, Tropical Spastic/enzymology , Paraparesis, Tropical Spastic/genetics , Paraparesis, Tropical Spastic/physiopathology , Spinal Cord/drug effects , Spinal Cord/metabolism , Spinal Cord/physiopathology , Spinal Cord Diseases/physiopathology , Treatment Outcome
8.
Birth Defects Res A Clin Mol Teratol ; 76(2): 86-95, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16463413

ABSTRACT

BACKGROUND: The retinoic acid (RA)-catabolizing enzyme Cyp26a1 plays an important role in protecting tailbud tissues from inappropriate exposure to RA. Cyp26a1-null animals exhibit caudal agenesis and spina bifida, imperforate anus, agenesis of the caudal portions of the digestive and urogenital tracts, and malformed lumbosacral skeletal elements. This phenotype closely resembles the most severe form of caudal agenesis in humans. In view of these findings, we investigated a potential involvement of the human CYP26A1 gene in the pathogenesis of caudal regression syndrome (CRS). METHODS: Mutational screening of 49 CRS patients and 132 controls was performed using denaturing high-performance liquid chromatography and sequencing. Differences in the genotype and allele frequency of each SNP were evaluated by chi(2) analysis. The biological significance of the intronic variants was investigated by transfection assays of mutant constructs and by analysis of the splicing patterns with RT-PCR. RESULTS: Mutational screening allowed us to identify 6 SNPs, 4 of which (447 C>G, 1134 G>A, IVS 1+10 G>C, and IVS 4+8 AG>GA) are new. In addition, we describe a novel 2-site haplotype consisting of the 2 intronic SNPs. Both single-locus and haplotype analyses revealed no association with increased risk for CRS. The consequences of the 2 intronic polymorphisms on the mRNA splicing process were also investigated. Moreover, using functional and computational methods we demonstrated that both of these intronic polymorphisms affect the intron splicing efficiency. CONCLUSIONS: Our research did not provide evidence that CYP26A1 has implications for the pathogenesis of human CRS. However, the relationship between CRS risk and the CYP26A1 genotype requires further study with a larger number of genotyped subjects.


Subject(s)
Cytochrome P-450 Enzyme System/genetics , DNA Mutational Analysis , Genetic Testing , Spinal Cord Diseases/genetics , Spinal Cord/abnormalities , Gene Frequency , Genotype , Humans , Magnetic Resonance Imaging , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Retinoic Acid 4-Hydroxylase , Risk Factors , Spinal Cord Diseases/enzymology , Spinal Cord Diseases/physiopathology
9.
Neurobiol Dis ; 18(2): 385-9, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15686967

ABSTRACT

Canavan disease (CD) is a neurodegenerative disorder characterized by the spongy degeneration of the white matter of the brain. Aspartoacylase (ASPA) gene mutation resulting enzyme deficiency is the basic cause of CD. Whether the ASPA defect in CD affects the spinal cord has been investigated using the ASPA gene knockout mouse. Luxol fast blue-hematoxylin and eosin staining in the spinal cord of the knockout mouse showed vacuolation in both white matter and gray matter areas of cervical, thoracic, lumbar, and sacral segments of the spinal cord. However, more vacuoles were seen in the gray matter than the white matter of the spinal cord. ASPA activity in the cervical, thoracic, lumbar, and sacrococcygeal regions of the spinal cord was significantly lower in the knockout mouse compared to the wild type. The enzyme defect in the knockout mouse was also confirmed using the Western blot method. These observations suggest that the ASPA gene defect in the mouse leads to spinal cord pathology, and that these changes may be partly involved in the cause of the physiological/behavioral abnormalities seen in the knockout mouse, if documented also in patients with CD.


Subject(s)
Amidohydrolases/deficiency , Canavan Disease/pathology , Spinal Cord Diseases/pathology , Spinal Cord/pathology , Amidohydrolases/genetics , Animals , Behavior, Animal/physiology , Canavan Disease/enzymology , Canavan Disease/genetics , Disease Models, Animal , Lameness, Animal/enzymology , Lameness, Animal/genetics , Lameness, Animal/pathology , Mice , Mice, Knockout , Mutation/genetics , Nerve Fibers, Myelinated/enzymology , Nerve Fibers, Myelinated/pathology , Neural Pathways/enzymology , Neural Pathways/pathology , Neural Pathways/physiopathology , Neurons/enzymology , Neurons/pathology , Spinal Cord/enzymology , Spinal Cord/physiopathology , Spinal Cord Diseases/enzymology , Spinal Cord Diseases/genetics , Vacuoles/pathology
10.
Brain Res Mol Brain Res ; 115(2): 173-86, 2003 Jul 23.
Article in English | MEDLINE | ID: mdl-12877988

ABSTRACT

The extracellular signal-regulated kinases (ERK) participate in numerous signaling pathways and are abundantly expressed in the CNS. It has been proposed that ERK activation promotes survival in models of neuronal injury. Inhibition of MEK, the upstream kinase that activates ERK, however, leads to neuroprotection in models of cerebral ischemia and trauma, suggesting that in this context ERK activation contributes to cellular damage. The effect of ischemia and reperfusion on activity and expression of ERK was investigated using a reversible model of rabbit spinal cord ischemia. Active ERK was observed in nai;ve animals, which decreased during 15 to 60 min of ischemia. Upon reperfusion, a robust activation of ERK was observed in animals occluded for 60 min that remained permanently paraplegic. Immunohistochemical analyses revealed increased staining of phosphorylated ERK (pERK) in glial cells and faint nuclear staining in motor neurons of animals occluded for 60 min and reperfused for 18 h. In contrast ERK activity did not increase in animals occluded for 15 min that regained motor function. No evidence of increased pERK immunoreactivity in motor neurons or nuclear translocation was noted in these animals. ERK1 was demonstrated to be identical to a p46 c-Jun/ATF-2 kinase previously shown to be activated by reperfusion after a 60-min occlusion. The results suggest that activation of ERK during reperfusion of ischemic spinal cord participates in the cellular pathways leading to neuronal damage.


Subject(s)
Ischemia/enzymology , JNK Mitogen-Activated Protein Kinases , Mitogen-Activated Protein Kinases/metabolism , Reperfusion/methods , Spinal Cord Diseases/enzymology , Activating Transcription Factor 2 , Animals , Cell Line , Cyclic AMP Response Element-Binding Protein/metabolism , Enzyme Activation , Hippocampus , Immunoblotting , Immunohistochemistry , Ischemia/metabolism , MAP Kinase Kinase 4 , Male , Mice , Mitogen-Activated Protein Kinase Kinases/metabolism , Myelin Basic Protein/metabolism , Phosphorylation , Precipitin Tests , Protein Kinases/metabolism , Rabbits , Subcellular Fractions/metabolism , Time Factors , Transcription Factors/metabolism
12.
J Neurol Sci ; 129 Suppl: 104-6, 1995 May.
Article in English | MEDLINE | ID: mdl-7595597

ABSTRACT

To investigate the mechanisms by which glutamate-induced acetylcholinesterase (AChE) release might play a part in the pathogenesis of excitotoxically triggered motor neurone disease, we measured AChE molecular forms released after glutamate-receptor agonist stimulation of superfused and incubated slices of mouse spinal cord. Kainate and GLU caused a dose-related, calcium-dependent, magnesium-blocked liberation of AChE soluble forms (mainly G4) from both the ventral and dorsal horns, without membrane damage. In the immature slice, glycine potentiated GLU elicited AChE release in the presence of strychnine, suggesting N-methyl-D-aspartate (NMDA) receptor involvement. After the 30th postnatal day, nearly all the release was caused by non-NMDA receptor stimulation. The response might interfere with the negative feedback loop which modulates the overactivation of motor neurones, and might render them more vulnerable to excitotoxic stress.


Subject(s)
Acetylcholinesterase/metabolism , Excitatory Amino Acid Agonists/toxicity , Glutamic Acid/toxicity , Receptors, Glutamate/physiology , Spinal Cord Diseases/chemically induced , Spinal Cord Diseases/enzymology , Animals , Glycine/pharmacology , Glycine Agents/pharmacology , In Vitro Techniques , Kainic Acid/toxicity , Mice , Receptors, Glutamate/drug effects , Strychnine/pharmacology
13.
Acta Physiol Hung ; 65(3): 255-62, 1985.
Article in English | MEDLINE | ID: mdl-4013764

ABSTRACT

Alterations in the dorsal root potential (DRP) which was evoked by stimulation of the common peroneal nerve of the rat, have been studied in the course of transganglionic degenerative atrophy (TDA) of primary sensory terminals in the upper dorsal horn. TDA was induced by perineural application of Vinca alkaloids around the sciatic nerve. In 9 to 30 days after this treatment, latency of DRP increased, whereas its amplitude and duration decreased. In this period, no C fibre response could be elicited. As a possible mechanism underlying the alterations of DRP, the functional consequences of atrophic changes of primary central afferent terminals are being discussed in terms of the close correlation between structure and function and the possible inferences of the electrophysiological reaction to the therapeutic application of Vinca alkaloids in the iontophoretic treatment of chronic intractable pain.


Subject(s)
Spinal Cord Diseases/physiopathology , Spinal Nerve Roots/physiopathology , Acid Phosphatase/metabolism , Animals , Atrophy , Electrophysiology , Histocytochemistry , Male , Nerve Degeneration , Rats , Rats, Inbred Strains , Spinal Cord/enzymology , Spinal Cord Diseases/enzymology , Spinal Cord Diseases/pathology
15.
J Neurol Neurosurg Psychiatry ; 46(11): 1031-6, 1983 Nov.
Article in English | MEDLINE | ID: mdl-6317805

ABSTRACT

Alpha and gamma enolase isoenzymes have been studied in 212 patients with a variety of neurological diseases. The results show that these proteins are sensitive markers of tissue damage which enable a distinction to be made between the involvement of glial and neuronal components.


Subject(s)
Isoenzymes/cerebrospinal fluid , Nervous System Diseases/enzymology , Phosphopyruvate Hydratase/cerebrospinal fluid , Brain Diseases/enzymology , Brain Neoplasms/enzymology , Cerebral Infarction/enzymology , Epilepsy/enzymology , Humans , Multiple Sclerosis/enzymology , Optic Neuritis/enzymology , Peripheral Nervous System Diseases/enzymology , Spinal Cord Diseases/enzymology
16.
J Neural Transm Suppl ; 19: 65-74, 1983.
Article in English | MEDLINE | ID: mdl-6142089

ABSTRACT

Altered metabolism of neuroexcitatory amino acids has been described in patients with a form of olivopontocerebellar atrophy (OPCA) associated with glutamate dehydrogenase (GDH) deficiency. To further investigate the specificity of these results, oral glutamate loading tests were performed in healthy controls, patients with GDH deficient OPCA as well as patients with non-GDH deficient degenerative disorders affecting primarily the function of the cerebellum and/or the basal ganglia. Following oral intake of monosodium glutamate, plasma levels of glutamate, aspartate and taurine increased significantly in controls and similar increases also occurred in patients with non-GDH deficient disorders. However, patients with GDH-deficient OPCA showed much greater elevations in plasma glutamate and aspartate and a rather flat taurine curve.


Subject(s)
Aspartic Acid/blood , Basal Ganglia Diseases/enzymology , Cerebellar Diseases/enzymology , Glutamates/blood , Sodium Glutamate , Spinal Cord Diseases/enzymology , Taurine/blood , Atrophy , Cerebellum/pathology , Friedreich Ataxia/enzymology , Glutamate Dehydrogenase/deficiency , Glutamic Acid , Humans , Nerve Degeneration , Olivary Nucleus/pathology , Parkinson Disease/enzymology , Pons/pathology , Shy-Drager Syndrome/enzymology
17.
Eur Neurol ; 22(1): 65-9, 1983.
Article in English | MEDLINE | ID: mdl-6301843

ABSTRACT

Adenylate kinase activity was measured in 41 samples of cerebrospinal fluid in 34 patients with various neurological disorders or psychiatric symptomatologies. Activities of the enzyme showed to be linked to clinically estimated acuteness or progression of the changes in the central nervous system at the time of specimen collection. The findings suggest the conclusion that determination of adenylate kinase activity in cerebrospinal fluid is a meaningful tool for the evaluation of progression and/or acuteness of central nervous system disorders.


Subject(s)
Adenylate Kinase/cerebrospinal fluid , Nervous System Diseases/enzymology , Phosphotransferases/cerebrospinal fluid , Adolescent , Adult , Brain Diseases/enzymology , Child , Child, Preschool , Female , Humans , Male , Nervous System Diseases/diagnosis , Neuromuscular Diseases/enzymology , Psychotic Disorders/enzymology , Spinal Cord Diseases/enzymology
18.
Neurochem Res ; 7(5): 627-36, 1982 May.
Article in English | MEDLINE | ID: mdl-6811963

ABSTRACT

Glutamate dehydrogenase (GDH) activity in leukocytes and platelets in spinocerebellar degenerations (SCD) was determined. In the same subject, GDH activity was higher and more reproducible in platelets than in leukocytes. GDH was decreased significantly in olivopontocerebellar atrophy (OPCA) (Ca. 30% decrease). Pyruvate dehydrogenase (PDH) in platelets showed non specific decreased activity in SCD and amyotropic lateral sclerosis. Energy metabolism in cerebellum may be diminished in some types of ataxia, and glutaminergic neurons may be more affected in OPCA than in other SCD.


Subject(s)
Cerebellar Diseases/enzymology , Glutamate Dehydrogenase/deficiency , Spinal Cord Diseases/enzymology , Adult , Atrophy/enzymology , Blood Platelets/enzymology , Cerebellar Ataxia/genetics , Cerebellum/pathology , Glutamate Dehydrogenase/blood , Humans , Leukocytes/enzymology , Middle Aged , Olivary Nucleus/pathology , Pons/pathology , Pyruvate Dehydrogenase Complex Deficiency Disease
19.
Neurology ; 32(5): 555-8, 1982 May.
Article in English | MEDLINE | ID: mdl-7200213

ABSTRACT

Incubation with dichloroacetate increased activity of the pyruvate dehydrogenase complex (PDHC) in disrupted fibroblasts from controls but not from two patients with autopsy-proved Leigh disease. These results are consistent with a genetically determined aberration of the regulation of PDHC in this disorder, although further studies are necessary to define the aberration.


Subject(s)
Brain Diseases/enzymology , Pyruvate Dehydrogenase Complex/metabolism , Spinal Cord Diseases/enzymology , Fibroblasts/enzymology , Humans , Skin
20.
J Am Vet Med Assoc ; 180(7): 743-6, 1982 Apr 01.
Article in English | MEDLINE | ID: mdl-6177674

ABSTRACT

The effects of dexamethasone on the pancreas and on pancreatic amylase and lipase activities were determined in clinically normal dogs and in dogs with neurologic disease. Dexamethasone increased serum lipase activity without any histologic damage to the pancreas in either group of dogs. It decreased serum amylase activity in the normal dogs and had a variable effect in dogs with neurologic disease, with or without confirmed pancreatitis. It was suggested that high serum lipase activity in dexamethasone-treated dogs may not be attributable to pancreatitis and that the reasons are still unknown. It was concluded that high serum lipase activity is an unreliable basis for diagnosis of pancreatitis in dogs treated with dexamethasone. The data allowed no conclusion about an additive effect of dexamethasone and neurologic disease causing pancreatitis.


Subject(s)
Amylases/blood , Dexamethasone/pharmacology , Dog Diseases/enzymology , Lipase/blood , Pancreas/drug effects , Spinal Cord Diseases/veterinary , Animals , Dexamethasone/adverse effects , Dexamethasone/therapeutic use , Dog Diseases/chemically induced , Dog Diseases/drug therapy , Dogs , Female , Male , Pancreatitis/chemically induced , Pancreatitis/veterinary , Spinal Cord Diseases/enzymology
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