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)

Human spongiform encephalopathies (HSEs) are transmissible diseases exclusively affecting the central nervous system. Sporadic Creutzfeldt-Jakob disease (CJD) constitute 85% of all forms of HSE. The origin of the disease is still unknown. A wide spectrum of diversely associated clinical symptoms are observed. Besides the typical rapidly progressive form which includes dementia, myoclonia, cerebellar ataxia, visual disturbances and periodic electroencephalography (EEG), other forms of the disease exist and may give rise to diagnostic difficulties. Periodic EEG or 14-3-3 protein detection in spinal fluid are helpful for diagnosis when clinical symptoms are present. Currently there is no presymptomatic test for diagnosis. Genetic CJD, Gerstmann-Straussler-Scheinker syndrome and Fatal Familial Insomnia are rarely observed and are always associated with a mutation or an insertion of the prion protein gene. The new variant of CJD is clinically characterized by psychiatric abnormalities, sensory symptoms and ataxia preceding dementia along with other features usually observed in sporadic CJD. Age of patient is abnormally low and duration of the illness is relatively long. Most of the cases are observed in the United Kingdom and a link with bovine spongiform encephalopathy is highly probable.
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PMID:Clinical aspects of human spongiform encephalopathies, with the exception of iatrogenic forms. 1022 Nov 63

Until recently, the clinical diagnosis of CJD relied mainly on three criteria. These include patient history (rapidly progressive dementia), neurological findings (ataxia, pyramidal/extrapyramidal signs, myoclonus, akinetic mutism) and typical electroencephalographic (EEG) findings. These criteria are fulfilled in typical cases. The occurrence or increase of certain proteins in cerebrospinal fluid (CSF; 14-3-3, neuron-specific enolase) now provide important adjuncts in recognizing variant forms. Although these proteins can be detected in other neurological diseases accompanied with substantial brain damage such as encephalitis, they are also characterized by their high sensitivity and specificity with regard to other dementing processes (Alzheimer and vascular dementia). The increase in the number of positive cases during the last years in Germany reflects an improved case ascertainment rather than the appearance of the variant CJD (vCJD). Although several recent cases with a long duration of the disease were actually recognized, they did not reveal the typical florid plaques at autopsy. They were revealed as a rare variant of sporadic CJD, which is characterized by homocygosity for valine at codon 129 and PrP(Sc) type 1. This variant is positive for the 14-3-3 protein in CSF. Further subtypes described by Parchi et al. can also be characterized by a certain pattern of clinical symptomatology, EEG- and 14-3-3-findings. In addition, differential diagnosis revealed some treatable dementias among the most common diseases (Alzheimer and vascular dementia) such as herpes encephalitis, multiple sclerosis and Hashimoto encephalitis, particularly in the younger age group.
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PMID:Clinical and differential diagnosis of Creutzfeldt-Jakob disease. 1121 18

Interactions between the checkpoint abrogator UCN-01 and several pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase (MEK)/MAPK pathway have been examined in a variety of human leukemia cell lines. Exposure of U937 monocytic leukemia cells to a marginally toxic concentration of UCN-01 (e.g., 150 nM) for 18 h resulted in phosphorylation/activation of p42/44 MAPK. Coadministration of the MEK inhibitor PD184352 (10 microM) blocked UCN-01-induced MAPK activation and was accompanied by marked mitochondrial damage (e.g., cytochrome c release and loss of DeltaPsi(m)), caspase activation, DNA fragmentation, and apoptosis. Similar interactions were noted in the case of other MEK inhibitors (e.g., PD98059; U0126) as well as in multiple other leukemia cell types (e.g., HL-60, Jurkat, CCRF-CEM, and Raji). Coadministration of PD184352 and UCN-01 resulted in reduced binding of the cdc25C phosphatase to 14-3-3 proteins, enhanced dephosphorylation/activation of p34(cdc2), and diminished phosphorylation of cyclic AMP-responsive element binding protein. The ability of UCN-01, when combined with PD184352, to antagonize cdc25C/14-3-3 protein binding, promote dephosphorylation of p34(cdc2), and potentiate apoptosis was mimicked by the ataxia telangectasia mutation inhibitor caffeine. In contrast, cotreatment of cells with UCN-01 and PD184352 did not substantially increase c-Jun-NH(2)-terminal kinase activation nor did it alter expression of Bcl-2, Bcl-x(L), Bax, or X-inhibitor of apoptosis. However, coexposure of U937 cells to UCN-01 and PD184352 induced a marked increase in p38 MAPK activation. Moreover, SB203580, which inhibits multiple kinases including p38 MAPK, partially antagonized cell death. Lastly, although UCN-01 +/- PD184352 did not induce p21(CIP1), stable expression of a p21(CIP1) antisense construct significantly increased susceptibility to this drug combination. Together, these findings indicate that exposure of leukemic cells to UCN-01 leads to activation of the MAPK cascade and that interruption of this process by MEK inhibition triggers perturbations in several signaling and cell cycle regulatory pathways that culminate in mitochondrial injury, caspase activation, and apoptosis. They also raise the possibility that disrupting multiple signaling pathways, e.g., by combining UCN-01 with MEK inhibitors, may represent a novel antileukemic strategy.
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PMID:Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells. 1143 48

The Creutzfeldt-Jakob disease (CJD) is rare spongiform encephalopathy. Its main symptoms are rapidly progressing dementia, myoclonic jerks, visual disturbances, ataxia, and pyramidal and extrapyramidal signs. A case of sporadic form of the CJD is reported, with blurred vision as one of the first symptoms. This symptom occurred shortly after vaccination against influenza, and was accompanied by other signs suggesting postvaccinal encephalitis. However, at a later stage of the disease typical changes were found in EEG recording and in magnetic resonance imaging (MRI). The presence of the 14-3-3 protein was detected in the patient's cerebrospinal fluid. The diagnosis of sporadic Creutzfeldt-Jakob disease was verified neuropathologically.
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PMID:[Diagnostic difficulties in Creutzfeldt-Jakob disease--case report]. 1517 42

Creutzfeldt-Jakob disease (CJD) is a presenile dementia characterized by rapidly progressive mental deterioration, myoclonic jerking, and other less common neurological signs. Few autoctonous cases have been described in Brazil. A 54-year-old white woman, was admitted in our service with a month history of progressive, bilateral cortical blindness. After admission, she developed right partial motor seizures( right facial, upper and lower limbs), she became progressively aphasic( mixed aphasia). Seizures were controlled with phenytoin, but she developed choreoathetotic movements on her right dimidium, with partial control after introduction of chlorpromazine 25 mg q/d. She could no longer stand up or walk due to severe ataxia. The first EEG (October, 2001) showed left hemisphere severe seizure activity (status epilepticus partialis). She was delivered home with enteral nutrition, phenytoin, chlorpromazine and mepacrine 100 mg qd. The following laboratorial tests were negative or normal: blood series, platelets, ESR, kidney and liver function, copper, ceruloplasmin, VDRL, HIV, HTLV-1, lactate, and cerebral DSA (performed in other service).A spinal tap with normal opening pressure was perform and CSF examination was normal. CSF 14-3-3 protein was positive, CSF specific neuronal enolase 7.5 ng/ml(normal). Genetic study of PRNP gene did not disclosed any known mutation. A MRI (October, 2001) showed areas of hyperintense signal (T2 and FLAIR) without Gd-enhancement on T1, in the left temporal lobe and in both occipital lobes; basal ganglia have a normal appearance. DWI imaging showed bright areas at the same sites. An EEG (March, 2002) disclosed a periodical sharp triphasic waves pattern, suggestive of CJD. A second MRI (April, 2002) showed mild generalized atrophy, no ventricular dilatation, and the hyperintense sites disappeared. She remained clinically stable and under use of chlorpromazine and mepacrine until she died due to pulmonary complications on April, 2003.
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PMID:[Creutzfeldt-Jakob disease, Heidenhain variant: case report with MRI (DWI) findings]. 1523 44

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive prion disease that causes deficits involving movement, cognition, and mental status. The clinical heterogeneity of the disease can make diagnosis difficult. Thorough neurologic, cognitive, and psychiatric examinations are necessary for observing its clinical features. In this case report we describe a 62-year-old male patient who was initially followed with a diagnosis of depression and later was diagnosed with CJD. The patient had a one-year history of anhedonia, loss of interest, social withdrawal, anxiety and decrease in speech and was given paroxetin 20 mg/day with a diagnosis of depression. During follow up, neurological symptoms including ataxia and rigidity became evident and dementia and akinetic mutism developed in a rapidly progressive course. Although electroencephalography (EEG) and magnetic resonance imaging (MRI) revealed nonspecific findings initially, typical findings for CJD were seen during the follow up. The positive 14-3-3 protein in CSF supported the diagnosis. The aim of this report is to emphasize the fact that CJD may present with different psychiatric symptoms and can be initially misdiagnosed. CJD should be considered in the differential diagnosis of patients who have focal neurological signs in addition to psychiatric symptoms. Repeated neurological examinations, EEG and cranial MRI may help in the diagnosis of these patients.
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PMID:[Creutzfeldt-Jakob disease: a case that initiated with psychiatric symptoms]. 1579 99

14-3-3 proteins form a family of highly conserved proteins which are present in all eukaryotic organisms investigated, often in multiple isoforms, up to 13 in some plants. They interact with more than 200 different, mostly phosphorylated proteins. The molecular consequences of 14-3-3 binding are diverse: this binding may result in stabilization of the active or inactive phosphorylated form of the protein, to a conformational alteration leading to activation or inhibition, to a different subcellular localization, to the interaction with other proteins or to shielding of binding sites. The binding partners, and hence the 14-3-3 proteins, are involved in almost every cellular process and 14-3-3 proteins have been linked to several diseases, such as cancer, Alzheimer's disease, the neurological Miller-Dieker and spinocerebellar ataxia type 1 diseases and bovine spongiform encephalopathy (BSE). The yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe both have two genes encoding 14-3-3 proteins, BMH1 and BMH2 and rad24 and rad25, respectively. In these yeasts, 14-3-3 proteins are essential in most laboratory strains. As in higher eukaryotes, yeast 14-3-3 proteins bind to numerous proteins involved in a variety of cellular processes. Recent genome-wide studies on yeast strains with impaired 14-3-3 function support the participation of 14-3-3 proteins in numerous yeast cellular processes. Given the high evolutionary conservation of the 14-3-3 proteins, the experimental accessibility and relative simplicity of yeasts make them excellent model organisms for elucidating the function of the 14-3-3 protein family.
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PMID:Yeast 14-3-3 proteins. 1649 3

In a patient with a rapidly progressive neurological condition with ataxia and cognitive complaints, Creutzfeldt-Jakob disease (CJD) is often high in the differential, particularly when there is an elevated CSF 14-3-3 protein level. We present a case of anti-glutamic acid decarboxylase antibody (anti-GAD65) positive cerebellar ataxia associated with cognitive complaints and elevated CSF 14-3-3 protein.
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PMID:Anti-GAD antibody cerebellar ataxia mimicking Creutzfeldt-Jakob disease. 1662 Dec 41

The authors investigated a 40-year-old woman who presented with ataxia and dementia with little progression for over 40 months. The results of a CSF 14-3-3 protein and EEG study did not reveal major abnormalities. Brain MRI showed increased signal intensity over the occipital cortex in diffusion-weighted imaging. To our knowledge, this is the longest MM-type sporadic Creutzfeldt-Jakob disease case with cortical kuru-type plaques.
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PMID:Long-duration sCJD with PRNP codon 129 methionine homozygosity and cerebral cortical plaques. 1670 28

Atypical clinical course and low sensitivity of established diagnostic tests are the main diagnostic problems in the MV2 subtype of sporadic Creutzfeldt-Jakob disease (sCJD). Clinical symptoms and signs, MRI, EEG and biochemical CSF markers were studied in 26 patients. Histological findings were semiquantitatively evaluated. Compared with typical sCJD, the disease duration was prolonged (median 12 months). Dementia, ataxia and psychiatric symptoms were present in all patients. Extrapyramidal signs were observed in 88%. T2-weighted MRI showed basal ganglia hyperintensities in 90%. Increased thalamic signal intensity was detected in 88% on diffusion-weighted MRI. Increased CSF tau-protein was found in 83%, and the 14-3-3 test was positive in 76%. The EEG revealed periodic sharp wave complexes in only two patients. Kuru plaques, severe thalamic and basal ganglia gliosis and spongiform changes, and neuronal loss in the pulvinar were the prominent histological features. At least one of the three diagnostic tests (MRI, tau- and 14-3-3 protein) supported the clinical diagnosis in all patients. MRI was the most sensitive of the diagnostic tests applied. Thalamic hyperintensities were observed unusually frequently. Prolonged disease duration, early and prominent psychiatric symptoms, absence of typical EEG, thalamic hyperintensities on MRI and relatively low 14-3-3 protein sensitivity may be suspicious for variant CJD. However, distinct sensory symptoms and young age at onset, which are often found in the latter, are not common in the MV2 subtype, and the pulvinar sign was observed in only one case.
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PMID:Clinical findings and diagnostic tests in the MV2 subtype of sporadic CJD. 1692 53


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