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

CBA/Ca mice injected with Plasmodium berghei develop cerebral malaria (CM) characterized by ataxia and progressive paralysis leading to death 7-9 days after experimental infection. The development of cerebral symptoms is a function of the immune response in susceptible strains, and depends on cell-cell interactions involving T helper cells and mononuclear phagocytes. Here we ask whether antibodies to cell adhesion receptors of the immune system can influence the development of CM in this mouse model. When administrated on day 6 after infection, antibody to the leukocyte integrin leukocyte function-antigen-1 (LFA-1) but not antibodies to MAC-1, LECAM-1 (the MEL-14 antigen), alpha 4 integrin or ICAM-1 dramatically reduced the incidence of CM, leading to survival of most mice until the later onset of anemia. Anti-LFA-1 treatment did not result in a substantial decrease in the monocyte accumulation observed in cerebral vessels of susceptible mice. Its efficacy may be related to the broader roles of LFA-1 in cell-cell interactions important in the later pathogenic stages of the immune response to the parasite. Perturbation of immune cell function through interference with cell adhesion mechanisms may offer an important therapeutic tool in acute, life-threatening immune-mediated disorders.
Eur J Immunol 1991 Sep
PMID:Late treatment with anti-LFA-1 (CD11a) antibody prevents cerebral malaria in a mouse model. 167 16

1. The behavioural effects of a selective cholecystokininB (CCKB) receptor antagonist CI-988 were investigated in rodents. 2. In three rodent tests of anxiety (rat elevated X-maze, rat social interaction test and mouse light/dark box) CI-988 over the dose range 0.001-10.0 mg kg-1, (i.p.) produced an anxiolytic-like action. The magnitude of this effect was similar to that of chlordiazepoxide (CDP). In contrast, the selective CCKA receptor antagonist, devazepide, was inactive. CI-988 also showed anxiolytic-like action in the rat conflict test but the magnitude of this effect was about 2.5 fold less than that of CDP. 3. Central but not peripheral administration of the selective CCKB receptor agonist, pentagastrin, like FG 7142, produced an anxiogenic-like action. 4. The pentagastrin-induced anxiety was dose-dependently antagonized by CI-988, whereas devazepide was inactive. However, ten times higher doses of CI-988 were required to block a similar action of FG 7142. 5. In contrast to CDP, CI-988 up to 3000 fold higher doses than those inducing anxiolysis was inactive in tests measuring sedation and ataxia. It also failed to antagonize pentylenetetrazol-induced tonic seizures. Furthermore, CI-988 did not interact with alcohol or barbiturates. Thus, CI-988 appears to be an anxioselective compound. 6. The anxiolytic-like action of CDP in the rat elevated X-maze was dose-dependently antagonized by flumazenil. In contrast, the benzodiazepine receptor antagonist failed to block a similar effect of CI-988. 7. Thus, CI-988 shows anxiolytic-like activity in several animal models of anxiety. The anxiolytic-like effect of CI-988 involves a novel mechanism of action, that is likely to be mediated by selective antagonism of the brain CCKB receptor. It is suggested that CI-988 should have a better side-effect profile in man than the benzodiazepines.
Br J Pharmacol 1991 Sep
PMID:The behavioural properties of CI-988, a selective cholecystokininB receptor antagonist. 168 5

The anticonvulsant potency of the trans isomer of 2-en-valproate (trans-2-en-VPA) was determined in standardized models for different seizure types in rodents and dogs. In mice and rats, adverse effects were quantified by the rotarod and chimney tests. Clinically established antiepileptic drugs (valproate, ethosuximide, phenobarbital, carbamazepine, phenytoin, diazepam) were used for comparison. Based on time course studies, drug potencies were determined and compared at the individual time of peak anticonvulsant effect. Potency comparisons were based on administered dosages and, in the case of trans-2-en-VPA and valproate, also on plasma levels determined after administration of anticonvulsant doses. The data show that trans-2-en-VPA exerts anticonvulsant effects against different seizure types, i.e., myoclonic, clonic, and tonic seizures in rodents and (myo)clonic seizures in dogs. In most seizure models, trans-2-en-VPA was more potent than valproate, when both compounds were compared at their individual times of peak effect. Time course and pharmacokinetic studies showed that duration of action and pharmacokinetic characteristics of trans-2-en-VPA and valproate are similar. In the rotarod and chimney tests in mice and rats, trans-2-en-VPA was more potent than valproate. However, because of the higher anticonvulsant potency of trans-2-en-VPA, protective indices calculated from rodent models were similar to those of valproate. Similarly, in dogs trans-2-en-VPA exerted anticonvulsant effects at doses below those which induced sedation and ataxia. In view of the previously reported advantages of trans-2-en-VPA compared to valproate with respect to teratogenic and hepatotoxic effects, the present data substantiate that trans-2-en-VPA might be a valuable alternative to valproate in antiepileptic therapy.
Epilepsy Res 1991 Sep
PMID:Trans-2-en-valproate: reevaluation of its anticonvulsant efficacy in standardized seizure models in mice, rats and dogs. 174 83

Of two brothers born of Sephardic first cousin parents one presented with congenital neural deafness, nyctalopia, visual field loss, flat ERG, unintelligible speech and a shuffling gait, and the other with severe ataxia, severe decreased visual acuity, mild field loss, decreased ERG, dysarthric speech and high grade myopia. The diagnosis of Usher syndrome type 1 or 2 is discussed as well as the possibility that both brothers have different genetic disorders.
Ophthalmic Paediatr Genet 1991 Sep
PMID:A hereditary syndrome with retinopathy and ataxia or deafness in two consanguineous brothers. 175 63

We studied the clinical records of 18 patients (11 female and 7 male), from 42-83 years old (average 66.1) who were operated for Normal Pressure Hydrocephalus. The etiology was idiopathic in 9 (50%), post-subarachnoid hemorrhage in 6 patients (33.3%), post-cerebral trauma in 2 (11.1%) and post-meningitis in 1. The patients were divided in 4 categories according to their symptoms, as follows: Group A: 9 patients (50%) with dementia, ataxia and incontinence. Group B: 1 patient (5.6%) with dementia-ataxia. Group C: 4 patients (22.2%) with ataxia and incontinence. Group D: 4 patients (22.2%) with ataxia only. 6 patients had a ventriculo peritoneal shunt, and 12 had a ventriculo-atrial shunt placed. All received a Hakim valve of low, medium or high pressure, according to the pre-op ventricular pressure. According to Stein and Langfitt scale for recovery 12 patients (66%) improved and 6 (33.3%) did not change. None was worse. There were no complications.
Rev Med Panama 1991 Sep
PMID:[Normal pressure hydrocephalus]. 176 37

A 69-year-old woman was admitted to our hospital on March 13, 1990, with a 1-month history of progressive gait disturbance. She had been operated on for colon cancer in May 1987. Examination in March 1989 revealed that she had metastatic liver tumor. On neurological examination, slight right abducens palsy, gaze-evoked horizontal nystagmus to the left, upbeat nystagmus and mild left hemiparesis were noted. Two weeks after admission, right lateral gaze palsy developed. Right MLF syndrome became apparent in the 3rd week. She was diagnosed as having one-and-a-half syndrome. Left hemi-hypesthesia and left limb ataxia were noted at that time. CT scan revealed ring-enhancing mass lesions in and around the right pontine tegmentum. Two weeks after development of the one-and-a-half syndrome, she became comatose with her eyes' conjugate deviation to the left and died on April 24, 1990. The metastatic lesions in both paramedian pontine reticular formation and medial longitudinal fasciculus were considered to be causative of her one-and-a-half syndrome. Clinical characteristics of 13 reported cases with one-and-a-half syndrome caused by brain tumor were reviewed. Half of them were caused by metastatic brain tumor.
Rinsho Shinkeigaku 1991 Sep
PMID:[One-and-a-half syndrome due to a brain tumor--a case report and review of the literature]. 176 50

Diseases affecting the cerebellum typically cause ataxia, coupled with dysmetria and tremor. Dysmetria is a condition in which there is improper measuring of distance in muscular acts; hypermetria is overreaching (overstepping) and hypometria is underreaching (understepping). Tremor refers to an involuntary, rhythmic, oscillatory movement of a body part. The tremor of cerebellar disease typically is exaggerated by goal-oriented movements (intention tremor). Cerebellar lesions also often cause loss of the menace response, despite the presence of normal vision. The anatomic basis for this phenomenon is obscure. The principal disease affecting the cerebellum in cats is cerebellar hypoplasia due to in utero infection with the panleukopenia virus. This disease will be discussed here. Neurologic signs of cerebellar involvement also may be seen in association with those diseases that affect the CNS multifocally. In these cats, there may be additional signs indicating involvement of other anatomic areas or the cerebellar deficits may occur alone (see discussion of multifocal diseases in Multiple Neurologic Deficits: Inflammatory Diseases [page 426] and Multiple Neurologic Deficits: Noninfectious Diseases [page 440]).
Probl Vet Med 1991 Sep
PMID:Ataxia, dysmetria, tremor. Cerebellar diseases. 180 62

Diseases affecting the vestibular system cause ataxia, characterized by head tilt, circling, falling, and rolling to the side of the lesion. Nystagmus occurs initially but may resolve. These clinical signs occur regardless of whether the lesion affects the peripheral or central portion of the vestibular system. Peripheral and central vestibular disorders are distinguished based on additional signs of brain stem involvement in the latter, as discussed in The Neurologic Examination and Lesion Localization on page 309. This distinction is critical in establishing both a differential diagnosis and prognosis in affected cats.
Probl Vet Med 1991 Sep
PMID:Ataxia, head tilt, nystagmus. Vestibular diseases. 180 63

A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1 +/- 5.4 years (27-47 years). The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP) were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded--0 = 0.02, z = (-2.17)--and the overall analysis of the lod scores suggest another chromosomal location than chromosome 6.
Arq Neuropsiquiatr 1991 Sep
PMID:Late onset autosomal dominant cerebellar ataxia. A family description and linkage analysis with the HLA system. 180 28

Methylmercury accumulates in the kidney and liver of rats, but fairly selectively damages the cerebellum, resulting in the clinical symptoms of neurological ataxia after prolonged exposures. Within the cerebellum, morphological examination indicated that the small granule cells beneath the Purkinje layer are especially susceptible to the toxin, showing signs of pyknosis during the phase of locomotory disability, whilst the large Purkinje cells are relatively resistant to cytotoxic injury. Flame photometric and electron probe X-ray microanalysis (EPXMA) of digested samples of the major organs failed to detect any significant changes in the Na, K, Ca, Mg, S and P concentrations of the organs, including the cerebellum, at intervals after methylmercury administration by either gastric gavage or via the drinking water. It was suggested that if the lesion within the cerebellum is restricted, as the morphological evidence suggests, to a small cohort of functionally important granule cells, then it may be difficult to detect elemental changes within this subpopulation against the compositionally unaltered majority of cerebellar cells and their extracellular spaces. To identify and compositionally characterize the injured cells requires electron probe X-ray microanalysis of frozen sections, or fractured bulk samples. The deep-seated nature of the 'target cells' within the cerebellum presents formidable cryopreparative problems.
Scanning Microsc 1991 Sep
PMID:An integrated study of the morphological and gross-elemental consequences of methyl mercury intoxication in rats, with particular attention on the cerebellum. 180 20


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