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N Nukina

Publications and source records attributed to N Nukina.

At least 55 records · Page 3Linked to original sources
PubMed1992

Immunohistochemical study of kuru plaques using antibodies against synthetic prion protein peptides.

Prion protein (PrP) is a protein closely associated with the transmission of scrapie and Creutzfeldt-Jakob disease (CJD). Kuru plaques are composed of this protein. PrP33-35 is converted to protease-resistant PrP27-30 by proteinase K digestion. It has not yet been determined which of these PrPs is present in kuru plaques in vivo. Accordingly we synthesized two peptides (peptide-N and peptide-M) that, respectively, corresponded to the protease-sensitive and protease-resistant portions of PrP33-35, based on the amino acid sequence deduced from human PrP cDNA. These two synthetic peptides were used to immunize rabbits and produce antisera (anti-N and anti-M). Both antisera stained kuru plaques in a patient with Gerstmann-Sträussler syndrome and one with CJD. Peptide-N has an amino acid sequence which does not exist in PrP27-30. Staining of kuru plaques by the antiserum against peptide-N indicated that the entire molecule, including the N-terminal portion of PrP33-35, was deposited in the kuru plaques.

Aged↗
PubMed1992

Accumulation of amyloid precursor protein and beta-protein immunoreactivities in axons injured by cerebral infarct.

To determine the distribution of amyloid precursor protein (APP), monoclonal antibodies against APP45-62 (APP1-28-9) and beta1-17 (4A18 and 4A61) were produced. In the sections of Alzheimer's disease (AD) brain, APP1-28-9 was reactive with neurites around senile plaques and a few neurons but not with amyloid cores. This antibody also immunostained the axons in the ischemic lesions of brain tissues from cases with cerebral infarct. 4A18 and 4A61 were reactive with amyloid plaques but not with neurites and neurons. The latter two antibodies also immunostained axons in ischemic lesions. These findings suggest that APP, transported by the fast axonal flows, accumulated in the injured axons in the central nervous system. The beta immunoreactivity appearing in those axons may provide a clue to the mechanism of amyloidogenesis.

Alzheimer Disease↗
PubMed1992

[Widespread tau abnormality in a case of cortico-basal degeneration].

A case with cortico-basal degeneration was reported with special reference to the immunohistochemical study. A 59-year-old housewife noted tremor and clumsiness of her left hand. On the initial examination she showed the hyperreflexia of the upper extremities and jaw jerk, parkinsonian symptoms such as Myerson sign, parkinsonian gait and rigidity in the left arm. She showed pronounced forced grasping in the left hand. At the age of 60 she showed a WAIS scale with verbal IQ of 99 and performance below the scale. She could not copy hand postures. Tremor was aggravated by action or anxiety, more prominent on the left hand. There was some incoordination on the finger-nose testing of left arm and on the knee-heel testing of both legs. She also showed homolateral dyskinesia. She had a left Babinski sign and sensory testing was normal. A CT scan showed slightly enlarged ventricles (Fig. 1). At the age of 61 she could not understand simple requests and speak few words spontaneously, showing severe dysarthria. There were palilalia and motor impersistence. CT scan showed more widening of the lateral ventricles. At the age of 62, she had lingual dyskinesia and tapping on her upper lip provoked myoclonic jerk on her arms. She died of pneumonia at the age of 65 years, 6 years from the onset. The brain weighed 1190 g. There were bilateral old subdural hematomas on the right parietal and occipital lobe and the left parietal lobe. There was atrophy of frontal and superior parietal region.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal Ganglia Diseases↗
PubMed1990

[Tau protein and beta protein].

The main pathological features of Alzheimer's disease are Alzheimer neurofibrillary tangles and senile plaques. Recent biochemical research revealed that tangles are composed of tau protein and ubiquitin and amyloid in senile plaques is composed of beta protein which is a fragment of the membrane receptor protein. Although fraction, other data suggest that whole molecules become abnormal and aggregate into PHF. On the other hand, beta protein is a small cleavage product of the precursor protein. It is not concluded yet whether abnormal precursor proteins exist or not. Recent research in this field is reviewed.

Adolescent↗
PubMed1990

[Chronic human colchicine myopathy].

We report a case of myopathy induced by daily administration of colchicine. A 65-year-old man with gout and renal dysfunction had taken 1 mg of colchicine daily for 3 years. The dose was raised to 2 mg per day and two months later, he developed progressive weakness of the proximal limbs and had difficulty in rising from squatting and climbing stairs. Five months after the development of weakness, neurological examination showed proximal muscle weakness without wasting, generalized hyporeflexia and mild sensory loss and dysesthesia of the toes. Serum creatine kinase level was elevated to 788 IU/L and creatinine level was 2.1 mg/dl. Electromyography demonstrated myogenic changes with spontaneous activity. HE preparations of biceps muscle biopsy showed mild increase of variation in fiber size, small vacuoles with and without basophilic rims in some fibers and a few fibers with unevenly stained sarcoplasm. NADH-TR preparations showed numerous moth-eaten and targetoid fibers. The small rimmed vacuoles stained positively for acid phosphatase. Electron microscopy showed accumulation of lysosomes and autophagic vacuoles, and architectural changes and disruptions of myofibrils. After the discontinuation of colchicine, his strength and serum CK level normalized within two masquerading as polymyositis, may occur when customary doses of colchicine are given daily to patients with renal dysfunction.

Aged↗
PubMed1989

The reinterpretation of the immunochemical study of Alzheimer neurofibrillary tangles.

Many studies have been done on neurofibrillary tangles occurring in Alzheimer's disease using antibodies, but without agreement on the interpretation of the results. Immunochemical studies using antibodies to neurofilament and tau and the antibody, Alz50, were carried out to estaslish a common view. The results suggest that: 1) antibodies to neurofilament recognizing tangles react with the phosphorylated epitope of tau in paired helical filaments; 2) Alz50 reacts with abnormal tau, which has slower electrophoretic mobility than normal tau; and 3) a certain part of tau has the protease-resistant property in brains affected by the disease.

Alzheimer Disease↗
PubMed1988

The monoclonal antibody, Alz 50, recognizes tau proteins in Alzheimer's disease brain.

The monoclonal antibody, Alz 50, is known to label many dystrophic neurites and neurofibrillary tangles in Alzheimer's disease (AD) brain. Using immunoprecipitation and immunoblotting, we have compared Alz 50 to monoclonal antibodies directed at two known components of neurofibrillary tangles, tau and ubiquitin, in order to characterize further the antigens recognized by Alz 50 in AD brain. Alz 50 labeled purified tau proteins in a highly similar fashion to two well-characterized tau monoclonal antibodies. Alz 50 precipitated proteins at the molecular weight of 50-70 kDa from AD but not normal brain; these proteins were reactive with the tau antibodies. In addition, Alz 50 precipitated proteins migrating principally around 160-180 kDa from AD but not normal brain; the relationship of the latter proteins to tau remains unclear. None of these proteins reacted with a ubiquitin antibody. We hypothesize that the proteins recognized by Alz 50 at much higher levers in AD than normal brain include modified and aggregated forms of tau.

Alzheimer Disease↗
PubMed1988

Studies on neurotransmitter markers of the basal ganglia in Pick's disease, with special reference to dopamine reduction.

gamma-Aminobutyric acid (GABA), substance P and dopamine concentrations and choline acetyltransferase (ChAT) activity were measured in post-mortem cerebrocortical and basal ganglial areas of 14 controls and 4 patients with pathologically verified Pick's disease (1 classic case and 3 cases of the generalized form). GABA and substance P levels in the substantia nigra and the globus pallidus were generally decreased, corresponding to the moderate to severe loss of small neurones in the striatum. ChAT activities in the striatum varied from case to case, in proportion to various degrees of loss of large neurones in the striatum. These neurotransmitter abnormalities in Pick's disease were exactly the same as those in Huntington's disease. However, dopamine concentrations were markedly reduced in the striatum in Pick's disease, whereas striatal dopamine in Huntington's disease is reported to be increased. A dopamine reduction in the striatum of Pick's disease was more disproportionately prominent than expected for various degrees of nigral cell loss. This may be one of the important factors which prevents the generation of choreic movements in Pick's disease in spite of definite striatal atrophy similar to Huntington's disease.

Adult↗
PubMed1987

Recognition of Alzheimer paired helical filaments by monoclonal neurofilament antibodies is due to crossreaction with tau protein.

Neurofibrillary tangles and senile plaques are the principal pathological features of Alzheimer disease. Neurofibrillary tangles and the neurites of senile plaques contain paired helical filaments (PHF) that consist of two 10-nm filaments twisted into a double helix. The precursor proteins of PHF are not fully known. To identify these precursors, numerous immunochemical studies have been carried out during the past decade. Two apparently conflicting results have been reported. (i) Some, but not all, monoclonal antibodies to neurofilaments stained neurofibrillary tangles. (ii) Polyclonal antibodies prepared to PHF purified in NaDodSO4 because of their unusual insolubility did not recognize normal proteins, including neurofilaments, on electrophoretic transfer blots of human brain homogenates. These results have been confirmed in several laboratories, including by the use of electron microscopic labeling. Recently, we reported that polyclonal PHF antibodies include antibodies to tau proteins, a family of heat-stable microtubule-associated phosphoproteins, and that antibodies to tau stain Alzheimer neurofibrillary tangles. Those monoclonal neurofilament antibodies that recognize tangles are reported to be directed against phosphorylated epitopes. These facts prompted us to reexamine certain neurofilament monoclonal antibodies that stain neurofibrillary tangles. All monoclonal neurofilament antibodies that stain tangles that we examined, including those initially reported, reacted with tau proteins. Our results suggest that these antibodies react with phosphorylated tau proteins in PHF, not neurofilament proteins, highlighting the problem of using antibodies to phosphorylated protein epitopes in immunochemical studies. Independent evidence for the presence of neurofilament proteins in human paired helical filaments is now required.

Alzheimer Disease↗
PubMed1986

One of the antigenic determinants of paired helical filaments is related to tau protein.

Paired helical filaments (PHF) are unusual neuronal fibers which accumulate progressively in the brain in Alzheimer's disease (AD). The insolubility of PHF in various kinds of solvents enabled us to obtain highly purified PHF, but prevented the application of conventional analytical methods to identify their components. Here we report that antibodies against purified PHF recognize tau protein, a brain-specific microtubule-associated protein, suggesting that a portion of PHF is tau protein.

Alzheimer Disease↗
PubMed1986

Phosphorylated tau protein is integrated into paired helical filaments in Alzheimer's disease.

Antisera to paired helical filaments (PHF) were found to contain a significant amount of tau antibodies specific for a phosphorylated form, but only a negligible amount of those specific for a non-phosphorylated form. Also, the phosphorylated tau-specific antibodies, but not the non-phosphorylated tau-specific ones, labeled neurofibrillary tangles isolated in the presence of sodium dodecyl sulfate (SDS) and stained both tangles and senile plaque neuritis in fixed tissue sections in a very similar way to as the whole antiserum did. Taken together, these results strongly suggest that a major antigenic determinant of PHF is phosphorylated tau itself.

Alzheimer Disease↗
PubMed1986

Expression of neurofilament triplet proteins in human neural tumors. An immunohistochemical study of paraganglioma, ganglioneuroma, ganglioneuroblastoma, and neuroblastoma.

Intermediate filaments which are specific to neural cells, ie, neurofilaments, consist of three subcomponents--68, 150, and 200 kd. Thirty human neural tumors were examined for the presence of these three subcomponents by means of their monospecific antisera. All 8 paragangliomas contained cells that were positive for the 68-kd component, but only 5 of them had cells positive for the 150-kd and 200-kd components. All 4 ganglioneuromas and 11 ganglioneuroblastomas contained cells that reacted with antibodies to all three components. All 7 neuroblastomas had cells reacting with antibody to 68 kd, but only 3 of them had cells that reacted with antibodies to 150 kd and 200 kd. In each case, the number of positive cells depended on the antibody used. The largest number reacting with antibody to 68 kd and the smallest with antibody to 200 kd. Furthermore, it was possible to detect tumor cells in which the 68-kd subcomponent existed by itself, but no tumor cells in which the 150-kd or 200-kd subcomponent existed alone could be detected. These results seem to indicate that antibody to the 68-kd component is sufficiently discriminating to be applied diagnostically.

Adult↗
PubMed1985

Studies on neurotransmitter markers and neuronal cell density in the cerebellar system in olivopontocerebellar atrophy and cortical cerebellar atrophy.

Glutamate, aspartate and gamma-aminobutyrate (GABA) concentrations and choline acetyltransferase (ChAT) activity were measured in postmortem cerebellar cortical areas and brainstem nuclei of 10 normal controls, 5 patients of olivopontocerebellar atrophy (OPCA) with multiple system atrophy (MSA) and 2 patients of cortical cerebellar atrophy (CCA). In addition, the neuronal cell density in the cerebellar cortex and the brainstem nuclei was determined, and the correlation between neurotransmitter markers and the neuronal cell densities were investigated. Glutamate and aspartate concentrations in the cerebellar cortical tissues were markedly varied from case to case of MSA (OPCA) and CCA patients. However, glutamate concentration in the anterior vermis showed a positive correlation coefficient with the density of granule cells (r = 0.554, 0.05 less than P less than 0.10) and, those in the posterior vermis and in the cerebellar hemisphere were positively correlated with cells in the inferior olive (r = 0.707 and 0.607, P less than 0.05, respectively). Aspartate concentration in the anterior vermis also has a positive correlation coefficient (r = 0.571, 0.05 less than P less than 0.10) with the density of cells in the inferior olive. GABA concentrations in the dentate nucleus were decreased in all cases of MSA (OPCA) and CCA, and were positively correlated with the degree of loss of Purkinje cells (r = 0.765, P less than 0.01). ChAT activities were decreased in certain cases of MSA (OPCA), but conversely, increased in CCA patients. ChAT activity in the posterior vermis has a positive correlation coefficient (r = 0.613, 0.05 less than P0.10) with the cell density in the pontine nucleus. A possibility of a compensatory increase of ChAT activity in CCA patients was discussed.

Adult↗
PubMed1985

Proteolytic fragments of Alzheimer's paired helical filaments.

We found that at least a part of Alzheimer's paired helical filaments (PHF) was cleaved by proteases to release three major polypeptides, the apparent molecular weights of which were 10K, 26K, and 36K daltons. These proteolytic fragments were strongly labeled with the antibodies specific to PHF. Absorption with highly purified PHF eliminated this labeling. The monospecific antibodies bound to the 10K daltons protein, the most intensely immunolabeled one, stained isolated neurofibrillary tangles composed of PHF. From these observations, we conclude that these polypeptides released by proteases, especially the 10K daltons protein, are derived from PHF themselves.

Alzheimer Disease↗