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 effects of weekly doses of transfer factor in four patients with ataxia--telangiectasia were investigated following a total course of 2 months therapy. Transfer factor administration showed no influence on the absolute lymphocyte counts, T-cell rosettes or antibody titres to EBV, but it caused conversion of skin-test reactivity and production of MIF to various antigens. There was a dissociation in blastic transformation response, the skin-test responses and MIF production. Serum interferon levels were low before, and 2, 6 and 24 hr after, therapy. Clinically no improvement in infections was observed following transfer factor therapy.
 ...
PMID:Transfer factor therapy in ataxia--telangiectasia. 20 9

Defective-interfering (DI) lymphocytic choriomeningitis virus (LCMV) prevented disease in the central nervous system produced by standard LCMV. Standard LCMV injected into Lewis rats two days after birth produced a disorder distinguishable clinically by weight loss and ataxia and histologically by infiltration of mononuclear cells and necrosis of the cerebellum. Concurrent injection of DI LCMV with standard LCMV prevented the disease and markedly reduced the synthesis of standard LCMV and of viral antigens in the brain. Because inhibition of viral synthesis occurred early (day 3) after infection and because no interferon activity could be demonstrated, it was concluded that the interference effect was likely due to DI virus-mediated homologous interference. Other experiments showed that DI LCMV blocked viral antigen synthesis in culture. The curtailed production of viral antigens and cytolytic standard virus by DI virus may play a role in control of acute and persistent viral infections.
 ...
PMID:Prevention of virus-induced cerebellar diseases by defective-interfering lymphocytic choriomeningitis virus. 90 77

A 75-year-old patient with metastatic renal cell carcinoma was treated with recombinant interferon alpha-C and thereafter developed a neurologic syndrome of dementia, ataxia, confusional state, loss of concentration ability and cortical blindness. CT scan findings were compatible with leukoencephalopathy, which is reported as being a toxic effect of interferon.
 ...
PMID:Interferon-related leukoencephalopathy in a patient with renal cell carcinoma. 174 62

As a part of studies on cell-mediated immune (CMI) responses of immunocompromised, Epstein-Barr virus (EBV)-infected patients who can or cannot restrict the proliferation of EBV-transformed B cells, we have studied 16 Turkish patients with ataxia-telangectasia (AT). Fifteen were EBV seropositive; one was seronegative. Among the seropositives, eight had no or only low anti-EBV-determined nuclear antigen (EBNA) antibody titers, while seven had normal anti-EBNA levels. EBV-seropositive and -seronegative healthy Turkish children were used as controls. We have particularly asked the question whether low EBNA antibody titers can be correlated with the level of EBV-specific and -nonspecific cell-mediated immunity. Non-EBV-specific tests included cell count, phenotypical characterization with monoclonal antibodies, assessment of natural killer (NK)-cell activity, and ability to suppress mitogen-induced immunoglobulin production. Two EBV-specific CMI tests were used: outgrowth inhibition (OI) and leukocyte migration inhibition (LMI). The majority of the patients of the low-EBNA antibody group was IgA deficient and had high levels of alpha-fetoprotein (a-FP). Cells reacting with OKT8 monoclonal antibody predominated in both AT patient groups. In contrast, the suppressor activity was present in only a few patients and NK and interferon-activated killing (IAK) activities were normal. EBV-specific cell-mediated responses were defective in seven of eight patients in the low-anti-EBNA group and five of seven patients in the group with normal anti-EBNA titers. It is concluded that AT patients are often defective in their EBV-specific cell-mediated immune responses and with regard to their EBNA antibody levels. These defects are associated with a predominance of T cells reacting with OKT8 monoclonal antibody.
 ...
PMID:Epstein-Barr virus (EBV)-specific cell-mediated and humoral immune responses in ataxia-telangectasia patients. 609 13

A mouse model for the study of postexposure prophylaxis of rabies was established. Mice injected intramuscularly with a street strain of rabies virus were significantly protected from death by five daily 0.2-ml doses of inactivated rabies vaccine of chick embryo cell culture origin initiated immediately or 3 hr after infection. In these mice, a large amount of circulating interferon was induced as early as 1 hr after the first dose of vaccine and lasted until at least 12 hr but no such amount of interferon was induced by additional doses of vaccine. Serum antibody was first detected in the mice on day 6. It was noted that some of the surviving mice manifested an ataxia or paralysis of the legs. Increasing mortality rates were shown in mice treated with decreasing doses of the vaccine. Passive protection tests using concentrated IgG and IgM antibodies with equivalent neutralization titers showed that IgG antibody gave total protection when given 24 hr before the infection, while it was almost totally ineffective in reducing the mortality when given 2 days or more after infection. IgM antibody did not protect the mice even when given 24 hr before infection. These results suggest that interferon production is more important than antibody production in the initial stages of protection by postexposure vaccination. However, the mechanisms of postexposure prophylaxis in this model could not be explained only by the interferon produced by the vaccine and the possible contributions of additional mechanisms were suggested.
 ...
PMID:A mouse model of the pathogenesis and postexposure prophylaxis of rabies. 616 50

A case of opsoclonus myoclonus ataxia shown not to be due to neuroblastoma was biologically and virologically studied. The presence of interferon was found in the patient's CSF. Its implication in the etiology of cerebellar ataxia is discussed.
 ...
PMID:[Presence of interferon in cerebrospinal fluid in nontumoral opsomyoclonic ataxia]. 619 88

The pathogenesis of human cerebral malaria (CM) remains unresolved. In the most widely used murine model of CM, the presence of T lymphocytes and/or interferon (IFN)-gamma is a prerequisite. IFN-gamma is the key inducer of indoleamine 2,3-dioxygenase (IDO), which is the catalyst of the first, and rate-limiting, step in the metabolism of tryptophan (Trp) along the kynurenine (Kyn) pathway. Quinolinic acid (QA), a product of this pathway, is a neuro-excitotoxin, like glutamic acid (Glu) and aspartic acid (Asp). Kynurenic acid (KA), also produced from the Kyn pathway, antagonizes the neuro-excitotoxic effects of QA, Glu, and Asp. We therefore examined the possible roles of IDO, metabolites of the Kyn pathway, Glu, and Asp in the pathogenesis of fatal murine CM. Plasmodium berghei ANKA infection was studied on days 6 and 7 post-inoculation (p.i.), at which time the mice exhibited cerebral symptoms such as convulsions, ataxia, coma, and a positive Wooly/White sign and died within 24 hours. A model for noncerebral malaria (NCM), P. berghei K173 infection, was also studied on days 6 and 7 and 13 to 17 p.i. to examine whether any changes were a general response to malaria infection. Biochemical analyses were done by high-pressure liquid chromatography and gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS). IDO activity was low or absent in the brains of uninfected mice and NCM mice (days 6 and 7 p.i.) and was induced strongly in the brains of fatal murine CM mice (days 6 and 7 p.i.) and NCM animals (days 13 to 17 p.i.). This induction was inhibited greatly by administration of dexamethasone, a treatment that also prevented CM symptoms and death. Furthermore, IDO induction was absent in IFN-gamma gene knockout mice, which were also resistant to CM. Brain concentrations of Kyn, 3-hydroxykynurenine, and the neuro-excitotoxin QA were significantly increased in both CM mice on days 6 and 7 p.i. and NCM mice on days 13 to 17 p.i., whereas an increase in the ratio of brain QA to KA occurred only in the CM mice at the time they were exhibiting cerebral symptoms. Brain concentrations of Glu and Asp were significantly decreased in CM and NCM mice (days 13 to 17 p.i.). The results imply that neuro-excitation induced by QA may contribute to the convulsions and neuro-excitatory signs observed in CM.
 ...
PMID:Dramatic changes in oxidative tryptophan metabolism along the kynurenine pathway in experimental cerebral and noncerebral malaria. 946 88

A 32-year-old Japanese male in his second remission of acute lymphoblastic leukemia (ALL) received a matched unrelated donor bone marrow transplant (BMT) from the Japan Marrow Donor Program. On day +83, a bone marrow examination revealed 5.2% leukemic cells. Despite the cessation of cyclosporine, leukemic cells in the bone marrow increased to 18.4% on day +91. Treatment was started with interferon (IFN)-alpha-2b 3 x 10(6) U/body s.c. daily on day +92 and leukemic cells in the bone marrow disappeared completely. The toxicity of IFN-alpha treatment included leukoencephalopathy consisting of somnolence, disorientation, short-term memory loss, lack of coordination and ataxia, myelotoxicity requiring multiple platelet transfusions and exacerbation of graft-versus-host disease (GVHD) of oral cavity, skin and lung. Because of progressive GVHD, IFN-alpha was discontinued on day +124. On day +132, a bone marrow aspirate showed 6.4% leukemic cells. The patient died of progressive ALL on day +178. IFN-alpha may be useful for the treatment of leukemic relapse following BMT, although its toxicity is marked.
 ...
PMID:Interferon-alpha treatment of acute lymphoblastic leukemia relapse after unrelated bone marrow transplantation. 959 46

This study focused on the in vitro infection of mouse and human neuroblastoma cells and the in vivo infection of the murine central nervous system with a recombinant measles virus. An undifferentiated mouse neuroblastoma cell line (TMN) was infected with the vaccine strain of measles virus (MVeGFP), which expresses enhanced green fluorescent protein (EGFP). MVeGFP infected the cells, and cell-to-cell spread was studied by virtue of the resulting EGFP autofluorescence, using real-time confocal microscopy. Cells were differentiated to a neuronal phenotype, and extended processes, which interconnected the cells, were observed. It was also possible to infect the differentiated neuroblastoma cells (dTMN) with MVeGFP. Single autofluorescent EGFP-positive cells were selected at the earliest possible point in the infection, and the spread of EGFP autofluorescence was monitored. In this instance the virus used the interconnecting processes to spread from cell to cell. Human neuroblastoma cells (SH-SY-5Y) were also infected with MVeGFP. The virus infected these cells, and existing processes were used to initiate new foci of infection at distinct regions of the monolayer. Transgenic animals expressing CD46, a measles virus receptor, and lacking interferon type 1 receptor gene were infected intracerebrally with MVeGFP. A productive infection ensued, and the mice exhibited clinical signs of infection, such as ataxia and an awkward gait, identical to those previously observed for the parental virus (Edtag). Mice were sacrificed, and brain sections were examined for EGFP autofluorescence by confocal scanning laser microscopy over a period of 6 h. EGFP was detected in discrete focal regions of the brain and in processes, which extended deep into the parenchyma. Collectively, these results indicate (i) that MVeGFP can be used to monitor virus replication sensitively, in real time, in animal tissues, (ii) that infection of ependymal cells and neuroblasts provides a route by which measles virus can enter the central nervous system in mouse models of encephalitis, and (iii) that upon infection, the virus spreads transneuronally.
 ...
PMID:In vitro and in vivo infection of neural cells by a recombinant measles virus expressing enhanced green fluorescent protein. 1093 5

Multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system (CNS), 2 results in damage to axons and their surrounding myelin sheath. The exact cause of inflammation remains unclear, but an autoimmune response directed against CNS antigens is suspected. MS can affect the brain, optic nerve and spinal cord, thus causing many neurological symptoms. These can include limb numbness or weakness, sensory or motor changes, ataxia, blurry vision, painful eye movements, bladder and bowel dysfunction, decreased memory, fatigue and effective disorders. This article will include a concise overview of the pathogenesis of MS in order to set the stage for subsequent discussion of the mechanisms of action of disease-modifying treatments, and whether these should influence our treatment choices. Although the exact pathogenesis of MS is not fully understood, current knowledge has already led to the development of effective treatments, namely interferon (IFN) 3 and glatiramer acetate, both of which have been shown to reduce relapse rates, while IFN 3- 1 a also reduces confirmed disability progression. Further increases in our understanding of the pathogenesis of MS are likely to assist in the identification of new targets for disease-modifying therapies and in the optimisation of current treatments..
 ...
PMID:What do we know about the mechanism of action of disease-modifying treatments in MS? 1554 50


1 2 3 Next >>