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)

Five percent of patients dying with breast cancer have leptomeningeal metastases (LM) but current therapy is of only marginal benefit. Therefore, an experimental model of LM from breast cancer was developed to facilitate the development of novel therapies. Cell suspensions of 13762 MAT BIII rat mammary carcinoma cells are injected into the cisterna magna of adult, female Fischer 344 rats under general anesthesia. 10-12 days after the injection of 2 x 10(5) viable cells, animals develop neurologic signs, including ataxia, paralysis and spontaneous rotation. Histologically, tumor cells can be seen in the subarachnoid space over the surface of the brain and spinal cord and within the ventricles. Tumor cells do not invade the brain parenchyma. Collections of tumor cells are extensively infiltrated by macrophages and CD8-positive (suppressor/cytotoxic) T cells, but by few CD4-positive (helper) T cells. MAT BIII cells therefore provide a model of LM from breast cancer with a reproducible clinical course and histologic features. The tumor elicits a cellular immune response and can be useful in exploring biologic therapies for leptomeningeal metastases.
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PMID:An experimental model of leptomeningeal metastases employing rat mammary carcinoma cells. 762 67

A patient with high titers of the anti-Ri antibody died 3 years after a progressive course with ataxia, opsoclonus, dementia, and peripheral neuropathy. At autopsy, no tumor was found. The nervous system exhibited severe Purkinje cell loss and contained perivascular and interstitial inflammatory infiltrates, particularly involving the brainstem. B and CD4 cells predominated in the perivascular spaces and CD8 cells in the interstitial infiltrates. Complement reactivity and natural killer cells were present and predominated in areas with more intense inflammatory infiltrates. Deposits of IgG were detected in the cytoplasm and nuclei of some neurons, particularly those in the brainstem tegmentum. The proportion of anti-Ri IgG in the total IgG extracted from various areas of the brain, serum, and cerebrospinal fluid was determined by quantitative western blot analysis. Anti-Ri reactivity was identified in immunoblots of all regions of the brain, but it predominated in basis pontis and dorsal mesencephalon. Our findings support the hypothesis of an autoimmune basis for the disorder and suggest that an antibody-mediated mechanism may play a role in its pathogenesis.
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PMID:Immunological and pathological study of anti-Ri-associated encephalopathy. 799 77

Aging is a physiological process that shares many behavioral, biochemical and neuroendocrine phenomena with the pathophysiological situation of unresolved stress, as well as with a pharmacologically induced syndrome resulting from chronic benzodiazepine (BZ) consumption. Behavioral findings include symptoms such as drowsiness, ataxia, fatigue, confusion, weakness, dizziness, vertigo, syncope, reversible dementia, depression, impairment of intellectual, psychomotor and sexual function, agitation, auditory and visual hallucinations, paranoid ideation, panic, delirium, depersonalization, sleepwalking, aggressivity, orthostatic hypotension, and insomnia. Neuroendocrine findings include: central depletion of noradrenaline (NA), dopamine, adrenaline (AD), and serotonin (5-HT); reduction in the ratio of circulating NA/AD as well as platelet 5-HT and increase of AD, plasma free 5-HT and cortisol. These disturbances together with the increased platelet aggregability observed in the three groups are typical of unresolved-stress situations. Immunological findings include significant reduction of peripheral T lymphocytes (CD3, CD4, CD8) and the CD4/CD8 ratio, CD16 and gamma-delta cells. On the other hand, the three groups (elderly subjects, subjects faced with unresolved stress, and BZ consumers) show increase of the CD57 lymphocyte subset as well as natural killer cytotoxicity. Alterations of several biological markers have also been found, specifically in the oral glucose tolerance test, the intramuscular clonidine test, and the supine/orthostasis/exercise test. From a clinical point of view, the three groups appear to be more susceptible to the appearance and progression of many acute and chronic diseases (infectious and malignant diseases). As a result, chronic consumption of BZs should be avoided in both the elderly and subjects in unresolved-stress situations.
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PMID:Benzodiazepines: tolerability in elderly patients. 884 97

Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. A primary cerebellar degeneration with HIV has not previously been reported. Ten patients were identified over an 8-year period at five medical centers. All patients had clinical, laboratory, and radiologic evaluations, and three had neuropathologic examinations. Patients presented with progressively unsteady gait, slurred speech, and limb clumsiness. Examination revealed gait ataxia, impaired limb coordination, dysarthria, and abnormal eye movements. Cognition, strength, and sensory function remained normal. CD4 lymphocyte counts varied between 10 and 437 cells/mm3. Neuroimaging studies showed prominent cerebellar atrophy. Neuropathology showed focal degeneration of the cerebellar granular cell layer and unusual focal axonal swellings in the brainstem and spinal cord. Cultures, histopathology, and immunochemical studies showed no conclusive evidence of infection. We report a syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection.
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PMID:Cerebellar degeneration associated with human immunodeficiency virus infection. 1069 Oct 12

Targeted expression of biologically active interleukin-12 (IL-12) in astrocytes of the central nervous system (CNS) results in spontaneous neuroimmunological disease of aged mice. Borna disease virus (BDV) can readily multiply in the mouse CNS but does not trigger disease in most strains. Here we show that a large percentage of IL-12 transgenic mice developed severe ataxia within 5 to 10 weeks after infection with BDV. By contrast, no disease developed in mock-infected IL-12 transgenic and wild-type mice until 4 months of age. Neurological symptoms were rare in infected wild-type animals, and if they occurred, these were milder and appeared later. Histological analyses showed that the cerebellum of infected IL-12 transgenic mice, which is the brain region with strongest transgene expression, contained large numbers of CD4(+) and CD8(+) T cells as well as lower numbers of B cells, whereas other parts of the CNS showed only mild infiltration by lymphocytes. The cerebellum of diseased mice further showed severe astrogliosis, calcifications and signs of neurodegeneration. BDV antigen and nucleic acids were present in lower amounts in the inflamed cerebellum of infected transgenic mice than in the noninflamed cerebellum of infected wild-type littermates, suggesting that IL-12 or IL-12-induced cytokines exhibited antiviral activity. We propose that BDV infection accelerates the frequency by which immune cells such as lymphocytes and NK cells enter the CNS and then respond to IL-12 present in the local milieu causing disease. Our results illustrate that infection of the CNS with a virus that is benign in certain hosts can be harmful in such normally disease-resistant hosts if the tissue is unfavorably preconditioned by proinflammatory cytokines.
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PMID:Borna disease virus accelerates inflammation and disease associated with transgenic expression of interleukin-12 in the central nervous system. 1241 61

Approximately 5,000 to 80,000 of the US service personnel involved in the Persian Gulf War have complained of a variety of nonspecific symptoms since their return in 1991. These symptoms have been collectively labeled Gulf War Illness and include muscle fatigue, general malaise, myalgia, impaired cognition, ataxia, headaches, fever, joint pain, skin rash, gastrointestinal disturbances, sleep disturbances, and respiratory difficulties. Exposures of military and service personnel were diverse and included the prescribed anti-nerve gas agent pyridostigmine bromide (PYR), N.N-diethyl-m-toluamide (DEET) insect repellent, and environmental exposures to jet fuel. Thus, studies in our laboratory were undertaken to determine if concurrent exposure to these agents, singly or in combination, would contribute to significant alterations in immunological function and disease susceptibility. To assess immune status, eight-week old B6C3F1 female mice were exposed for 14 days to single compounds or tertiary mixtures of 15.5 mg/kg DEET, 2 mg/kg PYR, and 500 mg/kg JP-8 (termed low dose), or 31 mg/kg DEET, 5 mg/kg PYR, and 1,000 mg/kg JP-8 (termed high dose). Immunosuppression was assessed 24 h after the last exposure. No remarkable alterations were evident in hematological parameters, spleen and thymus organ weight and total cellularity, natural killer (NK) cell activity, cytotoxic T-cell activity, or mitogen-induced lymphocyte proliferation after exposure to either single or tertiary mixtures at low or high doses. A few changes in CD4/CD8 flow cytometric lymphocyte subpopulations were detected after exposure to the tertiary mixture at the high dose. Delayed type hypersensitivity (DTH) was decreased by 88% after exposure to the high-dose mixture, and suppression of antibody-specific IgM immune responses (plaque-forming cell, PFC) occurred after exposure to all single and tertiary mixtures at both dose levels. In the PFC response, antagonism was apparent in the mixture, while coexposure to these agents resulted in a synergistic effect in the DTH response. Susceptibility to B16F10 tumor or Listeria monocytogenes challenge was not affected after single or tertiary exposures. These data suggest that combined exposure to DEET, PYR, and JP-8 does not profoundly alter many immunological endpoints, but does selectively target functional endpoints such as the PFC and DTH response. This should be considered when assessing human health risks in the military environment.
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PMID:Evaluation of immunotoxicity induced by single or concurrent exposure to N,N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel. 1253 64

Toxoplasmosis is the most common opportunistic infection of the central nervous system in patients with AIDS. The standard treatment for toxoplasmic encephalitis is pyrimethamine and sulfadiazine. There have been few reports of concurrent Toxoplasma brain abscess and cavitary Pneumocystis carinii pneumonia (PCP) in Taiwan. We report the case of a 26-year-old homosexual man with coexisting infection with Toxoplasma gondii and P. carinii who was successfully treated for brain abscess with clindamycin and sulfadiazine. The cavitary lung lesions, initially diagnosed as pulmonary tuberculosis, were proved to be PCP by lung biopsy. HIV infection and syphilis had been diagnosed 1 year before admission. He presented with general weakness, ataxia, nausea, blurred vision and fever for 2 weeks. Magnetic resonance imaging of the brain revealed multiple ring-enhanced lesions over the cerebrum and cerebellum. Chest roentgenography showed a 3-cm lesion with cavitation over the right upper lung field. Diagnostic computerized tomography-guided lung biopsy revealed P. carinii cysts. Clindamycin, sulfadiazine and trimethoprim (TMP)-sulfamethoxazole (20 mg/kg/day TMP) were given with good response. His CD4 count rose from 40 to 280/microL 4 months later. All antibiotics were discontinued after 4.5 months due to the development of a skin rash. He was well at follow-up 1 year later. This case suggests that the combination of clindamycin and sulfadiazine is an effective treatment for Toxoplasma brain abscess and highlights the importance of diagnostic lung biopsy for cavitary lung lesions, particularly in a region endemic for tuberculosis.
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PMID:Treatment of Toxoplasma brain abscess with clindamycin and sulfadiazine in an AIDS patient with concurrent atypical Pneumocystis carinii pneumonia. 1264 93

We describe changes in the immune system of the newly established mutant line, ataxia and male sterility (AMS) mouse, and that the putative ams mutation is independent of lpr but seemed to affect lymphoproliferation in its mother strain, MRL/lpr. The mean weights of the spleen and lymph nodes of ams-lpr double-homozygous mouse were reduced compared with lpr single-homozygous mouse. Comparison between ams single-homozygous and control mice revealed 45-50% reduction of the spleen weight in the former for which reduction of the number of nucleated cells contributed greatly. In the lymphocyte/monocyte fraction of the spleen, there were significant changes in the proportion of lymphocyte subpopulations, with a reduction of B cells, an increase in CD4 and CD8 T cells, and a decrease in the CD4 : CD8 ratio. In vitro response of splenocytes to concanavalin A showed inconspicuous dose- and time-dependent responses in ams homozygous spleen, suggesting functional alteration of the immunological response. Our results indicate that ams mutation affects the immune system in addition to its two other major effects on the central nervous system and male reproductive system.
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PMID:A new mutation, ataxia and male sterility (ams), of autoimmune-prone MRL/lpr mouse is not linked to lpr gene but associated with reduction of spleen size and alteration of lymphocyte subpopulations. 1278 14

We report four patients with ataxia-telangiectasia syndrome that presented varied neurologic evolution. Three patients initially presented neurologic alterations of slow progression, evolving to late immunocompromised conditions. The fourth patient presented, from symptom onset, immune and neurologic debilitation, that were both severe and of fast progression. The chronological sequence of the most commonly observed immunocompromised conditions were in our patients, in ascending order, IgA deficiency, IgG2 deficiency and the neutrophil phagocytosis stage and common variable immunodeficiency. The first two reports are of sisters in whom the diagnosis was done between the ages of three and six years, having ocular apraxia, cerebellar ataxia and telangiectasia. Slow progression of neurologic debilitation was observed, without presentation of intermittent infections. The patients began presenting accentuated immunocompromised conditions at the ages of 14 and 17 years, dying at the ages of 16 and 20 years, respectively, due to severe infections that were resistant to treatment. The diagnosis of the third case was established when the patient was two years old, presenting ataxia and telangiectasia. Syndrome progression was slow, presenting at the age of eight years more accentuated neurologic disorders and IgA deficiency. The fourth case presented significant neurologic compromise at the age of five, simultaneous to IgA and IgG2 deficiency, and repeating pneumonias and sinusitis. At this time, intravenous gammaglobulin reposition was done. The neurologic and immune disorders progressed rapidly, and at the age of eight presented the inability to walk. At this time inversion of the CD4/CD8 ration was verified through laboratory tests.
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PMID:Different clinical and laboratory evolutions in ataxia-telangiectasia syndrome: report of four cases. 1604 57

The exact immunopathogenesis and neuroanatomical localization of opsoclonus-myoclonus ataxia syndrome remains unclear. We describe a 1 year 9 month old girl who, shortly after commencement of highly active antiretroviral therapy developed opsoclonus-myoclonus syndrome and subsequently died of disseminated cytomegalovirus infection. We postulate on the etiological factors that may have played a role in the disease pathogenesis of the patient's opsoclonus-myoclonus ataxia. Immune reconstitution inflammatory syndrome was considered the most likely because of the initial CD4 depletion and the onset of symptoms shortly after initiation of antiretroviral therapy. Single photon emission computed tomography (SPECT) proved helpful by localizing the area of dysfunction to the cerebellar vermis.
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PMID:Opsoclonus-myoclonus in an HIV-infected child on antiretroviral therapy--possible immune reconstitution inflammatory syndrome. 1626 59


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