Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cerebellar cortex in patients with autosomal dominant and recessive ataxia was studied by Golgi impregnation and immunocytochemistry in order to gain further insight into the pathogenesis of neuronal atrophy which accompanies these disorders. Monoclonal antisera were used to visualize phosphorylated and non-phosphorylated neurofilament proteins, and a synapse-specific protein (P38; synaptophysin). Golgi stain and immunocytochemistry for non-phosphorylated neurofilament protein revealed partial or complete loss of distal Purkinje cell dendrities in the dominant cases and in one recessive case. Many preserved parallel fibres were shown by the monoclonal antibody to phosphorylated neurofilament protein. This antibody also gave strong reaction product in torpedoes. Axosomatic and axodendritic terminals on Purkinje cells were reduced in number, and loss of mossy fiber terminals was revealed by monoclonal anti-P38. The described methods provided additional morphological evidence of the heterogeneity of the hereditary ataxias. Purkinje cell atrophy progressed from loss and simplification of the dendritic tree to disappearance of the cell body. While these cells appeared to be especially vulnerable, other neurons of the molecular and granular layers were not exempt. There was evidence that at least some extracerebellar afferents, such as mossy fibers, were also affected by the disease process.
 ...
PMID:The Purkinje cell and its afferents in human hereditary ataxia. 206 16

With the recent epizootic of bovine spongiform encephalopathy in Europe, the differential diagnosis of neuronal vacuolation and spongiform change in other species has become critically important. Four Rottweiler puppies of both sexes, presented at 3-8 months of age, had clinical signs of generalized weakness and ataxia that started at 6 weeks of age. In all pups, neurologic examination detected an ataxia and tetraparesis, most severe in the pelvic limbs, and slowed proprioceptive placing reactions. Subsequently, there was rapid progressive neurologic deterioration, with severe placing deficits, knuckling, severe ataxia, and quadraparesis by 8 months of age. At necropsy, no gross lesions were observed. Microscopic lesions were restricted to the nervous system. The major lesion in all dogs was an intracytoplasmic neuronal vacuolation that was most prominent in the cerebellar roof nuclei and in nuclei of the extrapyramidal system. Similar vacuolation was found in neurons in both dorsal nerve root ganglia, myenteric plexus, and other ganglia of the autonomic nervous system. The single or multiple empty vacuoles were between 1 and 45 microm in diameter. A mild spongiform change was seen in the adjacent neuropil. Purkinje cell vacuolation and degeneration with segmental cell loss was seen in the oldest dog. In ventromedial and dorsolateral areas of the spinal cord white matter, there was mild bilaterally symmetrical axonal degeneration. Immunoblotting and immunocytochemical staining of the brain for protease-resistant scrapie prion protein was negative. All forms of vacuoles were negative for immunohistochemical staining with a variety of lectins. Ultrastructurally, the vacuoles were bound by a single membrane and contained granular material and sometimes membranous profiles. There was mild distension of the cytocavitary network but no unequivocal connection with the vacuoles was found. Axosomatic and axodendritic synapses in affected neurons were intact both ultrastructurally and with synaptophysin immunostaining. The clinicopathologic findings were different from those seen in the other neurologic diseases of Rottweilers. The age of the dogs, distribution and type of the lesions, ultrastructural findings, and negative immunoblotting most likely rule out the possibility of a scrapie agent-associated spongiform encephalopathy. However, the etiology of this new disease was not determined.
 ...
PMID:Neuronal vacuolation and spinocerebellar degeneration in young Rottweiler dogs. 968 79

In adult mice, administration of the anticonvulsive drug phenytoin caused focal swellings along the Purkinje cell axon correlated with ataxia and incoordination of movements. In our model, we used murine cerebellar slice cultures to study the influence of phenytoin on postnatal Purkinje cell axon differentiation. Almost all of our untreated cultures developed to mature-like cerebellar tissue. Immunohistochemistry with anti-calbindin-D28k or UCHTI (anti-CD3) antibodies revealed numerous Purkinje cell axons in the white matter. In the area of the deep cerebellar nuclei, immunolabelled axons formed a large axonal plexus. The few neurofilament-positive neurons in this area were densely covered with Purkinje cell axon terminals. The synaptophysin immunoreactivity revealed connections between the terminals and the neurons of the deep cerebellar nuclei. Treatment of cerebellar slice cultures with phenytoin (10-80 microM) for 10-16 days resulted in focal swellings of different size along the axon. The number of swellings increased with an increasing dosage. At concentrations of 40 microM phenytoin, Purkinje cell axons seemed to be unable to invade the deep cerebellar nuclei, but numerous aberrant, recurrent collaterals could be detected immunohistochemically with the two specific Purkinje cell antibodies. Possible cytotoxic effects after treatment, such as dendritic degeneration and a decrease in the number of immunolabelled Purkinje cells, were observed above 40 microM phenytoin. These data suggest that the response of juvenile Purkinje cells is dependent upon the dosage of the antiepileptic drug because of morphological alterations as well as a misrouting of previously established connections.
 ...
PMID:Phenytoin alters Purkinje cell axon morphology and targeting in vitro. 965 Jul 50

Dysembryoplastic neuroepithelial tumor (DNT), a benign neoplasm, is now a well recognized clinicopathological entity. We report the second case of DNT in the cerebellum occurring in a 20-year-old male presenting with ataxia. He also had Arnold-Chiari malformation of the adult type. Histologically the tumor was a "simple" DNT having the specific "glioneuronal" element, namely oligodendrocyte-like cells (OLCs), mucoid change and floating neurons (Purkinje cells). A striking feature was the perpendicular arrangement of the neuropil columns extending from the pial surface to white matter similar to those seen in supratentorial examples. On immunstaining some of the OLCs were positive for synaptophysin and negative for glial fibrillary acidic protein (GFAP), glucocerebroside, tau and MAP-2. The neuropil was synaptophysin-positive and focally positive for MAP-2 and GFAP as well. The Purkinje cells were morphologically normal but malaligned and were positive for phosphorylated neurofilament suggesting secondary dysplastic changes. A transition of the lesion into relatively normal cerebellum preserving the folial architecture was observed. The histological and immunochemical features of the DNT in cerebellum suggests its possible origin from the pluripotential external granular layer.
 ...
PMID:Infratentorial dysembryoplastic neuroepithelial tumor (DNT) associated with Arnold-Chiari malformation. 983 57

Spinocerebellar ataxia-1 (SCA-1), like other polyglutamine diseases, is associated with aggregation of mutant protein ataxin-1 in the nuclei of susceptible neurons. The role of ataxin-1 aggregates in the pathogenesis of susceptible neurons, especially cerebellar Purkinje cells, is unknown. The present study was initiated to determine the temporal relationship between ataxin-1 aggregation and the sequence of specific biochemical changes in Purkinje cells in SCA-1 transgenic mice (TM). Earlier, we demonstrated that SCA-1 TM with no Purkinje cell loss and no alterations in home cage behavior show decreased expression of calcium-binding proteins calbindin-D28k (CaB) and parvalbumin (PV) in Purkinje cells. To determine if increased expression of mutant ataxin-1 in TM is also associated with earlier biochemical changes in Purkinje cells, both heterozygous and homozygous (B05 line of SCA-1) TM were used. The age of onset of ataxia in SCA-1 TM was at 12 weeks in heterozygotes and 6 weeks in homozygotes. In 6 week old heterozygous TM, Western blot analysis of growth associated protein 43 (GAP-43) and synaptophysin revealed no significant alterations as compared with the age-matched nontransgenic mice (nTM), whereas CaB was significantly reduced. beta-III-Tubulin was used as a specific Purkinje cell marker protein, immunohistochemical localization showed strong beta-III-tubulin immunoreactivity (IR) in Purkinje cells in 6 week old heterozygous TM, whereas CaB and PV IR were markedly reduced in the same neurons (double immunofluorescence staining). Most Purkinje cells from heterozygous (12 weeks old) and homozygous (6 weeks old) TM contained ataxin-1 nuclear inclusions (NIs). Cells with and without visible NIs revealed reduced PV and CaB IR; however, the changes were overtly more severe in cells with visible NIs. In contrast, the same cells were strongly immunoreactive to beta-III-tubulin. CaB, which is also present in the nucleus, colocalized with ataxin-1 and ubiquitin positive NIs. Further, RT-PCR analysis of CaB mRNA in the cerebellum in 6 week old heterozygous TM demonstrated a significant decrease in mRNA in comparison with the aged-matched nTM. These data suggest that there are selective alterations in the expression of CaB and PV in Purkinje cells which possibly occur earlier than ataxin-1 aggregation. Further, we speculate that ataxin-1 aggregates may not be toxic in general; however, they may deplete specific proteins essential for Purkinje cell viability in SCA-1 TM.
 ...
PMID:Relationship between ataxin-1 nuclear inclusions and Purkinje cell specific proteins in SCA-1 transgenic mice. 1072 95

A granular cell tumor involving the pituitary gland, optic chiasm and ventral pyriform lobes was discovered in a 12-year-old Labrador Retriever. Clinical signs included acute blindness, seizures, ataxia, weakness, and behavioral changes. The diagnosis was established by histopathologic and ultrastructural examination of neoplastic tissues collected at necropsy. Granular cell tumors involving the central nervous system are well documented in humans but rarely have been described in dogs. The location of the neoplasm and the clinical symptoms seen in this dog closely parallel those of a rare syndrome in humans commonly described as symptomatic parasellar or pituitary granular cell tumors. The cell of origin for these tumors is still highly debated, and attempts to characterize human granular cell tumors through immunohistochemistry have produced conflicting results. An immunohistochemical profile of this neoplasm revealed focal positive staining for vimentin with a lack of staining for neuron-specific enolase, glial fibrillary acidic protein, S-100, and synaptophysin. All neoplastic cells were strongly positive with the periodic acid-Schiff reaction.
 ...
PMID:Symptomatic granular cell tumor involving the pituitary gland in a dog: a case report and review of the literature. 1135 66

Eleven cases of a distinctive tumor of the posterior fossa are described. The patients (age range 12-59 years) presented with headache and/or ataxia. Neuroimaging revealed a relatively discrete, focally enhancing mass(es) primarily involving the aqueduct, fourth ventricle, and cerebellar vermis. Hydrocephalus was present in seven cases, and two lesions were multicentric. In two cases a significant increase in tumor size was documented. Gross total or subtotal resections were achieved in 10 cases. One patient underwent biopsy alone and another received postoperative irradiation. Histologically, two components were identified in all cases. One consisted of neurocytes forming neurocytic and/or perivascular pseudorosettes in a fibrillary, partly microcystic matrix. The second, astrocytic component resembled pilocytic astrocytoma in 10 cases and consisted of fibrillated spindle cells with oval nuclei associated with occasional Rosenthal fibers, granular bodies, glomeruloid capillaries, and microcalcifications. Regionally, this component was more diffuse and patternless, consisting of sheets of round to oval, oligodendrocyte-like cells. Rare ganglion cells were seen in four cases. The rosettes were consistently synaptophysin and MAP-2 immunoreactive, whereas the spindle cells were positive for S-100 protein and glial fibrillary acidic protein. Overall, atypia was minimal; no mitoses were found, and Ki67 labeling indices were low. Ultrastructurally, the neurocytic cells featured processes containing microtubules and occasional dense core granules. Mature synapses were found in one of the four cases studied. Although the histologic features of this unique tumor superficially resemble those of dysembryoplastic neuroepithelial tumor, rosette formation by neuronal cells, the frequent presence of a pilocytic astrocytoma component, and the growing nature of the lesion argue against that diagnosis, as does occasional multifocality.
 ...
PMID:A rosette-forming glioneuronal tumor of the fourth ventricle: infratentorial form of dysembryoplastic neuroepithelial tumor? 1197 88

A 3-year-old Staffordshire Terrier was presented to the Texas Veterinary Medical Center with a short progressive history of anorexia, weight loss, and weakness that had progressed to ataxia and collapse with empirical treatment. The dog was tetraparetic and obtunded. Results of a complete neurologic evaluation were consistent with severe, multifocal to diffuse disease involving the forebrain, spinal cord, and brainstem. Cerebrospinal fluid, obtained via cerebellomedullary cisternal puncture, was highly cellular and contained large atypical round cells with small numbers of nondegenerate neutrophils and large mononuclear cells. Rare eosinophils and small lymphocytes were noted. The atypical round cells were approximately 15-25 micro m in diameter with a single nucleus set in a small amount of cytoplasm. The nuclei were typically round to slightly ovoid; however, occasional notched, lobulated, and reniform nuclei were observed. These cells were interpreted as malignant lymphocytes. Owing to a grave prognosis, the animal was euthanized and a necropsy was performed. No gross lesions were found in the central nervous system. Multiple sections of cerebellum, medulla, and spinal cord contained a diffuse neoplastic infiltrate that was predominantly meningeal with rare superficial neuropil invasion. The neoplastic cells were arranged in sheets, cords, and rosettes. Immunohistochemical staining for vimentin, pancytokeratin, CD3, CD79a, synaptophysin, S-100, and neuron-specific enolase was negative; glial fibrillary acidic protein (GFAP) staining was equivocal. Based on histologic findings, a diagnosis of medulloblastoma was made. This case documents the rare occurrence of a canine medulloblastoma and illustrates the difficulty in distinguishing between some embryonal brain tumors and lymphoma.
 ...
PMID:Cerebrospinal fluid from a dog with neurologic collapse. 1296 66

We have generated a mouse model system with a high incidence of medulloblastoma, a malignant neoplasm believed to arise from immature precursors of cerebellar granule neurons. These animals ectopically express interferon-gamma (IFN-gamma) in astrocytes in the CNS in a controlled manner, exploiting the tetracycline-controllable system. More than 80% of these mice display severe ataxia and develop cerebellar tumors that express synaptophysin, the mouse atonal homolog MATH1, sonic hedgehog (SHH), and Gli1. IFN-gamma-induced tumorigenesis in these mice is associated with increased expression of SHH, and SHH induction and tumorigenesis are dependent on signal transducer and activator of transcription 1 (STAT1). When IFN-gamma expression is shut down with doxycycline at postnatal day 12 (P12), the clinical symptoms dissipate and the mice do not develop tumors, whereas if transgene expression is shut down at P16, the clinical symptoms and tumors progress to lethality, indicating that IFN-gamma is required for tumor induction but not progression. The tumors that occur in the continued presence of IFN-gamma display extensive necrosis and apoptosis as well as macrophage and lymphocytic infiltration, whereas the tumors that develop in mice in which IFN-gamma expression is shut down at P16 do not. Thus, IFN-gamma expression in the perinatal period can induce SHH expression and medulloblastoma in the cerebellum by a STAT1-dependent mechanism, and its continued presence appears to promote a host response to the tumor.
 ...
PMID:Interferon-gamma induced medulloblastoma in the developing cerebellum. 1553 76

Medulloblastoma is a malignant invasive embryonal tumor of the cerebellum with preferential manifestation in children. The peak of occurrence is seven years of age. Seventy percent of medulloblastomas occur in individuals younger than 16. In adulthood, 80% of medulloblastomas arise in the 21-40 years age group. A 48-year-old male patient was admitted to the hospital with complains of headache, ataxia, morning vomiting and difficulty in speech was operated with the diagnosis of presence of mass of 4 x 7 cm size retaining a diffuse homogenous contrast in the posterior fossa. The diagnosis of desmoplastic medulloblastoma was given after histopathological examination. Immunohistochemical examination revealed that neoplastic cells showed staining with neuron-specific enolase and synaptophysin but not with glial fibrillary acidic protein. This lesion showed nodular, reticulin free-zones (pale islands) surrounded by densely packed, highly proliferative cells. The pale regions within the tumor did not contain reticulin fibers. Desmoplastic medulloblastoma is encountered especially in adulthood. This type of tumor rarely occurs beyond the fifth decade of life. We present a case of desmoplastic medulloblastoma in a 48-year-old male.
 ...
PMID:Desmoplastic medulloblastoma in a 48-year-old male. 1557 57


1 2 3 Next >>