Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report concerns an autopsy case of rapidly progressive aphasia and motor neuron disease. The patient was a Japanese woman who was 75 years old at the time of death. The family history did not reveal hereditary burden. She developed language disturbances and difficulty in swallowing at age 74. Neurological examination 1 month after the disease onset revealed motor aphasia without dementia and bulbar sign, followed by muscle weakness of the four extremities. Neuroradiological examination revealed progressive atrophy of the anterior part of the left temporal lobe. She died of respiratory difficulty 10 months after the disease onset. Macroscopically, neuropathological examination showed circumscribed atrophy of the left perisylvian region and, histologically, neuronal loss in the cerebral cortex, including the primary motor area, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to obvious degeneration of the pyramidal tracts and presence of Bunina bodies. Ubiquitin-immunoreactive neuronal inclusions were present in the hippocampal dentate granular cells and frontotemporal cortical layer II neurons. Based on these clinicopathological findings and a review of the literature, we concluded that our case is the first reported case of amyotrophic lateral sclerosis with dementia that clinically showed rapidly progressive aphasia.
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PMID:Rapidly progressive aphasia and motor neuron disease: a clinical, radiological, and pathological study of an autopsy case with circumscribed lobar atrophy. 1065 Oct 32

Between 1993 and 2001, we observed fifteen patients (ten men and five women, mean age 63 years) with frontotemporal dementia (FTD) which preceded signs of amyotrophic lateral sclerosis (ALS) which developed 21 months later. Mean disease duration in the fourteen deceased patients was 38 months. FTD associated with ALS is characterized by rapid course, predominance of disinhibited forms (orbito-basal), presence of aphasia with neologisms, and semantic memory disorders. Performed in all patients, single-photon emission computed tomography demonstrated a bifrontal pattern of low uptake, sometimes associated with low uptake in the anterior temporal region. In one patient, neuropathology revealed neuron atrophy and loss in the frontotemporal region, the anterior horns, and the hypoglossal nucleus. Ubiquitin-positive inclusions were visible in the dentate gyrus of the hippocampus and in the anterior horns. The dementia/ALS association is classically described is uncommon. It belongs to the FTD group since the Lund and Manchester consensus. Approximately 15 p.100 of patient with FTD can be expected to develop ALS. About 250 cases have been reported in the literature, half of them in the Pacific area where the incidence of ALS is high (55/100,000 inhabitants versus 1/100,000 in the rest of the world). Intermediary forms of FTD, semantic dementia, and progressive non-fluent aphasia are discussed since several cases of non-fluent progressive aphasia associated with ALS are reported in the literature. The links between these two degenerative diseases are discussed.
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PMID:[Neuropsychological and scintigraphic aspects of frontotemporal dementia preceding amyotrophic lateral sclerosis]. 1277 98

We report an autopsy case of dementia lacking distinctive histology (DLDH) showing semantic dementia. At age 47, a Japanese man developed aspontaneity, followed by semantic dementia a few months after the onset. Thereafter he developed disinhibition and the language disturbance, which progressed transcortical sensory aphasia and terminally mixed transcortical aphasia. At age 48, about 10 months after the disease onset, neurological examination revealed frontal signs and hyperreflexia in the four extremities and 4 months later, the patient presented with mild rigidity in the right upper and lower extremities. At age 49, 1 year and 8 months after the onset of the disease, he could not walk by himself. At age 50, 2 years and 8 months after the onset, he died of pneumonia. The brain weighed 1350 g. Macroscopically, atrophy of the frontal lobes and temporal lobes, predominant in the left, was evident. The caudate nucleus was severely atrophic, in addition to the depigmentation of the substantia nigra. Neuronal loss and astrocytosis was obvious in the cerebral cortex, prominently in the frontotemporal lobes, amygdala, caudate nucleus, putamen, pallidum, thalamus, and substantia nigra. In the caudate nucleus, prominent neuronal loss with fibrillary gliosis was obvious. Senile plaques, neurofibrillary tangles, Pick bodies, astrocytic plaques, and tufted astrocytes were not found by Gallyas and tau staining. Ubiquitin-immunoreactive intracytoplasmic inclusions were not encountered in the hippocampal dentate gyrus and superficial layers in the frontotemporal cortex. On the basis of meticulous perusal of the literature, we believe that our case is the first autopsy case of DLDH reported in Japan.
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PMID:[An autopsy case of dementia lacking distinctive histology showing semantic dementia]. 1591 59

A patient with progressive anomia and alexia with agraphia for kanji (Japanese morphograms) is described. The patient showed a deficit in single-word comprehension and on-reading (a type of reading that conveys phonetic value) dominance in kanji reading, i.e. on-preceding (pronouncing first with on-reading, irrespective of its preferred reading) and kun-deletion (inability to recall and recognize kun-reading [another type of reading that conveys meaning]) when reading a single-character kanji. These features were due to loss of lexico-semantic information and thus the patient was regarded as having progressive Gogi (word-meaning) aphasia by Imura, a Japanese manifestation of semantic dementia. Macroscopically, neuropathological examination disclosed atrophy of the left frontotemporal lobe with accentuation in the anterior portion of the temporal lobe. Histologically, there was neuronal loss in the cerebral cortex, hippocampus, parahippocampal gyrus, amygdala, caudate nucleus, and putamen. Ubiquitin-immunoreactive neuronal inclusions were present in the hippocampal dentate granular cells. This case demonstrates that progressive Gogi aphasia is semiologically identical to semantic dementia, and our patient clinicopathologically resembled those of Rossor et al. [Rossor, M.N., Revesz, T., Lantos, P.L., Warrington, E.K. Semantic dementia with ubiquitin-positive tau-negative inclusion bodies. Brain 2000; 123: 267-76.] and Hodges et al. [Hodges, J.R., Davies, R.R., Xuereb, J.H., Casey, B., Broe, M., Bak, T.H., et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol 2004; 56: 399-406.].
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PMID:Ubiquitin-positive frontotemporal lobar degeneration presenting with progressive Gogi (word-meaning) aphasia. A neuropsychological, radiological and pathological evaluation of a Japanese semantic dementia patient. 1704 99

The history and classification of frontotemporal lobar degeneration (FTLD) are reviewed in this paper. After Pick's descriptions, there are confusions regarding the classification of the clinical syndromes and the underlying histological changes of frontotemporal lobe degeneration of the non-Alzheimer type. In 1994, the Lund and Manchester groups proposed clinical and neuropathological criteria for the classification of frontotemporal dementia (FTD); frontal lobe degeneration type, Pick-type, and motor neuron disease (MND) type. Ubiquitin-positive and tau-negative inclusions in the extra-motor neurons were characteristic of MND type and were first described by us. In 1996 and 1998, Neary et al. proposed the concept of FTLD to facilitate diagnosis and provide diagnostic criteria for 3 clinical syndromes associated with FTLD, namely, FTD, progressive nonfluent aphasia, and semantic dementia. In 2001, an international group of clinical and basic scientists reassessed the clinical and neuropathological criteria for the diagnosis of FTD and recommended revised neuropathological criteria for diagnosis. In 2007, Cairns et al. proposed another version of the criteria for pathological diagnosis of the neurodegenerative group of diseases termed as FTLD on the basis of the recent advances in molecular genetic, biochemical, and neuropathological studies. According to these criteria, FTLD is mainly divided into 2 groups-tauopathies and TDP-43 proteinopathies-on the basis of immunohistological methods.
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PMID:[History and classification of frontotemporal lobar degeneration]. 1993 76

Frontotemporal dementia (FTD) is one of the commonest forms of early-onset dementia, accounting for up to 20% of all dementia patients. Recently, it has been shown that mutations in progranulin gene (PGRN) cause many familial cases of FTD. Members of a family affected by FTD spectrum disorders were ascertained in Poland and Canada. Clinical, radiological, molecular, genetic, and pathological studies were performed. A sequencing analysis of PGRN exons 1-13 was performed in the proband. Genotyping of the identified PGRN mutation and pathological analysis was carried out in the proband's brother. The onset of symptoms of FTD in the proband included bradykinesia, apathy, and somnolence followed by changes in personality, cognitive deficits, and psychotic features. The proband's clinical diagnosis was FTD and parkinsonism (FTDP). DNA sequence analysis of PGRN revealed a novel, heterozygous mutation in exon 11 (g.2988_2989delCA, P439_R440fsX6). The mutation introduced a premature stop codon at position 444. The proband's brother with the same mutation had a different course first presenting as progressive non-fluent aphasia, and later evolving symptoms of behavioral variant of FTD. He also developed parkinsonism late in the disease course evolving into corticobasal syndrome. Pathological analysis in the brother revealed Frontotemporal Lobar Degeneration-Ubiquitin (FTLD-U)/TDP-43 positive pathology. The novel PGRN mutation is a disease-causing mutation and is associated with substantial intra-familial clinical heterogeneity. Although presenting features were different, rapid and substantial deterioration in the disease course was observed in both family members.
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PMID:Intra-familial clinical heterogeneity due to FTLD-U with TDP-43 proteinopathy caused by a novel deletion in progranulin gene (PGRN). 2093 Feb 69