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N Nukina

Publications and source records attributed to N Nukina.

At least 19 recordsLinked to original sources
PubMed1995

Monoclonal antibody against the polymorphic site distinguishes apolipoprotein E4 from other isoforms.

Apolipoprotein E4 has been confirmed as a genetic risk factor for Alzheimer's disease. Although several hypotheses have been advanced to explain how the inheritance of apolipoprotein E isoforms affects the rate of Alzheimer's disease expression, the mechanism whereby apolipoprotein E is involved in the pathogenesis of Alzheimer's disease is still uncertain. To clarify the way in which the apolipoprotein E4 isoform differs from the others, we generated a monoclonal antibody specifically reactive with the apolipoprotein E4 isoform. This antibody suggests that the polymorphic site is important in differentiating the ApoE4 isoform from others.

Alzheimer Disease↗
PubMed1995

Abnormal gene product identified in Huntington's disease lymphocytes and brain.

Huntington's disease(HD) is associated with expansion of an unstable CAG repeat. Using antibodies against the synthetic peptide corresponding to the sequence of HD gene IT15, we have identified the HD gene product in normal lymphocytes as a approximately 350kDa protein by immunoblot analysis. Moreover, when a modified SDS-PAGE using a low concentration of methylenbisacrylamide was run longer, abnormal immunoreactive bands larger than normal ones were found exclusively in HD samples. These results demonstrate the existence of the expanded CAG repeat gene product and open a possibility that the expanded polyglutamine stretch may really participate in the pathological process of the CAG repeat diseases.

Amino Acid Sequence↗
PubMed1995

Abnormal gene product identified in hereditary dentatorubral-pallidoluysian atrophy (DRPLA) brain.

Dentatorubral-pallidoluysian atrophy (DRPLA) is associated with the expansion of an unstable CAG repeat. Using antibodies against a synthetic peptide corresponding to the sequence of the DRPLA gene product C terminus, we have identified the DRPLA gene product in normal human brains as a approximately 190 kD protein. We also find a larger approximately 205 kD protein specifically in DRPLA brains. Immunohistochemically, the DRPLA gene product is observed mainly in the neuronal cytoplasm. Our results demonstrate the existence of the expanded CAG repeat gene product and support the possibility that the expanded CAG-encoded polyglutamine stretch may participate in the pathological process of the similar trinucleotide repeat diseases.

Adult↗
PubMed1995

[Dementia].

Explore the source record for details and available documents.

Aged↗
PubMed1994

APP717 missense mutation affects the ratio of amyloid beta protein species (A beta 1-42/43 and a beta 1-40) in familial Alzheimer's disease brain.

We have biochemically purified A beta from brains of two unrelated familial Alzheimer's disease (FAD) pedigrees with the APP717 mutation (Val-->Ile) and from two sporadic Alzheimer's disease (AD) brains and characterized them by means of mass spectrometry and enzyme-linked immunosorbent assay. We observed two types of amyloid beta protein (A beta), the short-tail form (A beta 1-40) and the long-tail form (A beta 1-42/43), in sporadic AD and FAD brains, and found that the ratio of the long-tail form of A beta (A beta 1-42/43) to total A beta was increased in FAD brains. These in vivo results were confirmed in vitro using cultured cells transfected with three kinds of APP cDNAs bearing the APP717 mutations (Val-->Ile, Gly, or Phe). Taken together with the hypothesis that A beta 1-42/43 functions as a "seed" that increases the kinetics of amyloid fibril formation (Jarrett, J. T., and Lansbury, P. T., Jr. (1993) Cell 73, 1055-1058), we conclude that the APP717 missense mutation does not create new A beta species but promotes the increased accumulation of A beta 1-42/43 in the brain, which results in the enhancement of amyloid fibril formation from soluble A beta. These findings provide a causal relationship between this FAD genotype and the pathological phenotype of A beta deposition and senile plaque formation.

Adult↗
PubMed1994

Cerebellar ataxia and polyneuropathy in a patient with IgM M-protein specific to the Gal(beta 1-3)GalNAc epitope.

A 79-year-old man with sensory dominant polyneuropathy, cerebellar ataxia, and palatal myoclonus had serum IgM M-protein that specifically bound to GM1, GD1b, and asialo-GM1. IgM with the same specificity was detected in his cerebrospinal fluid. Results of immunohistochemical studies showed specific binding of this monoclonal IgM to the cerebellar granular layer, dentate nucleus, inferior olive, and gray matter of the cerebrum and spinal cord. Monoclonal antibody GGR12, monospecific to GD1b, had an immunostaining distribution similar to that of the patient's IgM M-protein. The binding of M-protein may be associated with the development of cerebellar ataxia and palatal myoclonus in this patient.

Aged↗
PubMed1994

Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43).

To learn about the carboxy-terminal extent of amyloid beta-protein (A beta) composition of senile plaques (SPs) in the brain affected with Alzheimer's disease (AD), we employed two end-specific monoclonal antibodies as immunocytochemical probes: one is specific for A beta 40, the carboxyl terminus of A beta 1-40, while the other is specific for A beta 42(43). In the AD cortex, all SPs that were labeled with an authentic antibody were A beta 42(43) positive, while only one-third of which, on the average, were A beta 40 positive. There was a strong correlation between A beta 40 positivity and mature plaques. Two familial AD cortices with the mutation of beta-amyloid protein precursor 717 (beta APP717) (Val to Ile) showed a remarkable predominance of A beta 42(43)-positive, A beta 40-negative plaques. Diffuse plaques, representing the earliest stage of A beta deposition, were exclusively positive for A beta 42(43), but completely negative for A beta 40.

Adult↗
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↗