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Biomedical subjects

Y Takehisa

Publications and source records attributed to Y Takehisa.

At least 19 recordsLinked to original sources
PubMed2001

Lead content of brain tissue in diffuse neurofibrillary tangles with calcification (DNTC): the possibility of lead neurotoxicity.

Diffuse neurofibrillary tangles with calcification (DNTC) is a form of presenile dementia, characterized pathologically by fronto-temporal atrophy with neurofibrillary tangles (NFTs), neuropil threads and Fahr-type calcification, in which no senile plaques are observed. As already noted, chronic exposure to lead (Pb) might be one of the etiological factors of Fahr-type calcification. Until now, there have been no reports in which Pb concentration has been quantified in DNTC brains. We examined the concentration of Pb in fresh-frozen brain tissue and in 10% formalin-fixed brain tissue from six cases of DNTC, four cases of Alzheimer's disease, and in nine non-demented elderly controls by flameless atomic absorption spectrometry, and demonstrated a high concentration of Pb in DNTC brains. Although it remains unclear how these findings are related to the formation of NFTs, they suggest that Pb neurotoxicity may be involved in the pathogenesis of DNTC.

Aged↗
PubMed2001

Diffuse neurofibrillary tangles with calcification (a form of dementia): X-ray spectrometric evidence of lead accumulation in calcified regions.

Diffuse neurofibrillary tangles with calcification (DNTC) is a form of slowly progressive dementia in which no senile plaques are observed. The calcification is one of the most characteristic features of DNTC. We examined the elemental content of certain mineral deposits (lead, magnesium, phosphorus, calcium, iron, copper and zinc) in the calcified and non-calcified regions of eight cases of DNTC, five cases of Alzheimer's disease (AD) and in eight non-demented elderly controls. The study was performed using a combination of scanning electron microscopy and X-ray spectrometry on 10% formalin-fixed brain tissue. A marked abundance of calcium and phosphorus was observed in the calcified regions of DNTC and non-DNTC brains. Although no lead was observed in the non-calcified regions of DNTC and in non-DNTC brains, traces of lead were detected exclusively in the calcified regions of DNTC brains. The implications and possible significance of the lead accumulation in DNTC brains are discussed.

Aged↗
PubMed2001

Increased expression of synaptophysin and stathmin mRNAs after methamphetamine administration in rat brain.

The rearrangement of neural networks associated with the behavioral sensitization induced by psychostimulants is poorly understood. We have investigated the effect of methamphetamine (METH) administration on the mRNA levels of three different classes of plasticity-related genes in the rat brain. The expression of synaptophysin mRNA increased 20-40% in the nucleus accumbens, prefrontal and temporal cortices, 1-24 h after acute METH administration, and that of stathmin mRNA increased about 20% in the prefrontal cortex 1 h later. They did not change after subchronic administration. The level of alpha-tubulin mRNA was constant. Therefore, synaptophysin and stathmin play an important role in the neural plastic changes involved in the early induction process of METH-induced sensitization, but not in the later maintenance process.

Animals↗
PubMed2001

Association study of CAG repeats in the KCNN3 gene in Japanese patients with schizophrenia, schizoaffective disorder and bipolar disorder.

To investigate a possible involvement of expanded triplet repeats of genome in the genomes of patients with endogenous psychoses, we examined a CAG repeat polymorphism in the coding region of the KCNN3 gene in schizophrenia, schizoaffective disorder, bipolar disorder and controls of the Japanese population. There were no significant differences in the CAG repeat number of longer or shorter alleles among the four diagnostic groups or among the schizophrenia hebephrenic and paranoid subtypes.

Adenine↗
PubMed2001

NOTCH4 gene polymorphism and susceptibility to schizophrenia and schizoaffective disorder.

The NOTCH4 gene is located at 6p21.3, a site which several studies have shown to have significant linkage with schizophrenia. Recently, an exceptionally strong association was reported between NOTCH4 gene polymorphisms and schizophrenia in British patients. We re-examined their findings using a Japanese population. We genotyped three kinds of polymorphisms, SNP1 in the 5' flanking region, SNP2 in the promoter region and CTG repeats in exon 1 of the NOTCH4 gene of schizophrenics (N=188), patients with schizoaffective disorder (N=39) and controls (N=143). Genotypic distributions and allelic frequencies of SNP1, SNP2 and CTG repeats of the NOTCH4 gene did not show significant associations with schizophrenia or schizoaffective disorder. Neither they showed association with schizophrenia subcategories, hebephrenic and paranoid type schizophrenia, nor with subgroups of schizophrenia with and without positive family history of psychoses. The present study found that the NOTCH4 gene does not confer susceptibility to schizophrenia and schizoaffective disorders, at least in Japanese subjects, in contrast to the findings in British subjects.

Adult↗
PubMed2001

Familial amyotrophic lateral sclerosis with a novel Leu126Ser mutation in the copper/zinc superoxide dismutase gene showing mild clinical features and lewy body-like hyaline inclusions.

BACKGROUND: Mutations in the SOD1 gene are responsible for approximately 25% of all familial amyotrophic lateral sclerosis (ALS) cases. However, the correlation between the clinical and pathological features and the various SOD1 gene mutations has not been well characterized. OBJECTIVES: To screen the SOD1 gene in search of potential mutations and to obtain clinical and pathological data for 2 Japanese families with ALS. DESIGN: Clinical histories and neurological findings, gross and microscopic pathological features, and DNA analysis of the SOD1 gene. RESULTS: The 2 families with ALS showed a novel missense mutation in the SOD1 gene, which was heterozygous for point mutation TTG to TCG, causing substitution of leucine for serine at codon 126 (Leu126Ser) in exon 5. Clinically, patients showed slower disease progression and lack of upper motor neuron signs. Neuropathologically, the autopsied patient showed the form of familial ALS with posterior column involvement, and the pontocerebellar tract and the dentate nuclei of the cerebellum were also involved. Furthermore, abundant Lewy body-like hyaline inclusions were observed in the affected motor and nonmotor neurons. CONCLUSIONS: Familial ALS with a novel Leu126Ser mutation in the SOD1 gene showed mild clinical features and lack of upper motor neuron signs. We believe that Leu126Ser might be associated with the clinical features and that the mutation site in the SOD1 gene and disease duration might be associated with the formation of Lewy body-like hyaline inclusions.

Adult↗
PubMed2001

A family with X-linked dystonia-deafness syndrome with a novel mutation of the DDP gene.

BACKGROUND: X-linked dystonia-deafness syndrome (DDS) is characterized by early-onset deafness followed by progressive dystonia in adulthood. Only 4 families with the syndrome have been reported, and all were white. OBJECTIVE: To describe the first nonwhite family with X-linked DDS, involving 5 affected males in 4 generations. RESULTS: Clinical features of the family members, who were Japanese, were mostly consistent with reports of DDS in whites except for a lack of visual disturbances. Whereas microdeletions in the deafness-dystonia peptide (DDP) gene were found in 2 white DDS families, our patients showed a novel mutation (arg80ter) in exon 2 of the DDP gene. CONCLUSION: The existence of a DDS family of Japanese origin with a new kind of mutation in the DDP gene provides additional evidence that the DDP gene is a causative gene for X-linked DDS.

Adolescent↗
PubMed2001

Plaque-like structures and arteriosclerotic changes in "diffuse neurofibrillary tangles with calcification" (DNTC).

"Diffuse neurofibrillary tangles with calcification" (DNTC) is a rare form of slowly progressive dementia characterized by temporal or fronto-temporal atrophy with neuronal loss and astrocytosis, neurofibrillary tangles and Fahr-type calcification, but no senile plaques in the cerebral cortex. In patients with DNTC, we detected a novel histopathological abnormality that we termed "plaque-like structures" (PLS). PLS appeared as oval, slightly eosinophilic masses of up to 100 microns in diameter. With methenamine silver stain, the PLS were argyrophilic, and thread-like structures were observed in and around them. Most PLS were observed in deep layers of the cortex and subcortical white matter, and were accompanied by small vessels. They were intimately associated with the small-vessel walls and astrocytes. They were composed of two types of fibers. The first type comprised straight and loosely interwoven fibers about 25-30 nm in diameter, while the other type evoked tangles. These structures have not been found in other neurodegenerative diseases, including Alzheimer's disease. In addition, to evaluate hyaline arteriosclerosis in DNTC, we examined sclerotic changes of the medullary arteries and assessed white matter lesions in affected patients. In three of four patients with DNTC, sclerosis of the medullary arteries was significantly more extensive than in age-matched controls. In all four patients, the severity of white matter lesions was graded as moderate or severe in the temporal lobe and as mild or moderate in the frontal lobe. Arteriosclerotic changes and white matter lesions can occur without hypertension and beta amyloid deposits in DNTC.

Amyloid beta-Peptides↗
PubMed2001

Two kinds of mitogen-activated protein kinase phosphatases, MKP-1 and MKP-3, are differentially activated by acute and chronic methamphetamine treatment in the rat brain.

Two functionally different MAP kinase phosphatases (MKPs) were investigated to clarify their roles in behavioral sensitization to methamphetamine (METH). MKP-1 mRNA levels increased substantially by about 60-300% in a range of brain regions, including several cortices, the striatum and thalamus 0.5-1 h after acute METH administration. After chronic METH administration its increase was less pronounced, but a more than 50% increase was still seen in the frontal cortex. MKP-1 protein levels also increased 3 h after acute or chronic METH administration. MKP-3 mRNA levels increased by about 30-50% in several cortices, the striatum and hippocampus 1 h after acute METH administration, but only in the hippocampus CA1 after chronic METH administration. Pre-treatment with the D(1) dopamine receptor antagonist, SCH23390, attenuated the METH-induced increase of MKP-1 and MKP-3 mRNA in every brain region, while pre-treatment with the NMDA receptor antagonist, MK-801, attenuated it in some regions. These findings suggest that in METH-induced sensitization, MKP-1 and MKP-3 play important roles in the neural plastic modification in widespread brain regions in the earlier induction process, but in the later maintenance process, they do so only in restricted brain regions such as MKP-1 in the frontal cortices and MKP-3 in the hippocampus.

Acute Disease↗
PubMed2000

Tau-negative astrocytic star-like inclusions and coiled bodies in dementia with Lewy bodies.

To evaluate glial lesions in cases of dementia with Lewy bodies (DLB), we studied the brains of four patients with DLB. Astrocytic star-like inclusions, which resembled tufted astrocytic fibrillary tangles in shape, were found in the cortex of two of these cases. In addition, coiled bodies were found in the white matter of the cerebrum in two cases. The astrocytic star-like inclusions were immunohistochemically negative for tau protein, ubiquitin and alpha-synuclein. The coiled bodies were immunohistochemically negative for tau protein but immunopositive for ubiquitin and alpha-synuclein. These results suggest that in DLB a primary degenerative process takes place in both glial cells and neurons.

Aged↗
PubMed2000

An autopsy case of postencephalitic parkinsonism of von Economo type: some new observations concerning neurofibrillary tangles and astrocytic tangles.

An autopsied case of postencephalitic parkinsonism of von Economo type with a 71-year duration is reported. Several cases of postencephalitic parkinsonism of von Economo type have been reported in Japan but this is the first reported case from western Japan. The patient was a Japanese man who was 74 years of age at the time of death. He developed encephalitis of unknown etiology at the age of 3 years. The first symptom was antisocial behavior, which developed at 30 years of age. At the age of 40 years, the patient showed progressive parkinsonism. Neuropathological findings disclosed marked neuronal loss with gliosis in the substantia nigra, locus ceruleus, and raphe nuclei, as well as the appearance of neurofibrillary tangles in the aforementioned areas. There were also widespread tuft-shaped astrocytes (Tu-SA) in the central nervous system, including the thalamus. Tuft-shaped astrocytes are considered to represent non-reactive astrocytes because the distributions of neurofibrillary tangles (NFT) and Tu-SA are clearly different. Therefore, the primary astrocytic lesions in postencephalitic parkinsonism of von Economo type may be more widespread. Ultrastructurally, the Tu-SA consisted of straight filaments, 15 nm in width, which formed tight bundles. Ultrastructurally, NFF in this case revealed paired helical filaments but straight filaments, 15 nm in width, which were also found in the neurons of the substantia nigra.

Aged↗
PubMed1998

Schizophrenic psychoses and the CNTF null mutation.

Genetic susceptibility plays an important role in the development of schizophrenic psychoses, and the neural maldevelopment hypothesis is suggested by neuropathological and neuroimaging findings. We investigated the association between a null mutation in the ciliary neurotrophic factor (CNTF) gene and functional psychoses including schizophrenia and schizoaffective disorder. The frequency of mutant allele was significantly increased in patients with schizoaffective disorder, but not in those with schizophrenia in comparison with controls. The CNTF null mutation resulting in CNTF deficiency may confer potential susceptibility to schizoaffective disorder.

Adult↗
PubMed1997

[Evaluation of conjunctival epithelial damage in dry eye].

Using sulphorhodamine B, which is highly sensitive in detecting damaged ocular surface epithelium, we evaluated conjunctival epithelial damage in dry eye patients. The subjects were 99 eyes of 50 dry eye patients (41 eyes of 21 patients with Sjögren's syndrome and 58 eyes of 29 keratoconjunctivitis sicca patients without Sjögren's syndrome). We also investigated the relation between sulphorhodamine B and fluorescein staining in ocular surface epithelium. The conjunctival epithelial damage stained with sulphorhodamine B showed a high correlation with corneal epithelial damage stained with fluorescein. In addition, conjunctival damage in Sjögren's syndrome tended to be more severe than in patients without Sjögren's syndrome.

Adolescent↗
PubMed1996

Correlation of tear lipid layer interference patterns with the diagnosis and severity of dry eye.

PURPOSE: To observe and classify tear film lipid layer interference patterns in normal volunteers and dry eye patients and to investigate the relation between the lipid layer interference patterns in the dry eyes and the results of other dry eye examinations. METHODS: Precorneal tear lipid layer interference patterns were observed at the central cornea in 25 eyes of 13 normal controls and 85 eyes of 48 dry eye patients. Observed patterns were classified in masked fashion by five physicians into five grades: grade 1, somewhat gray color, uniform distribution; grade 2, somewhat gray color, nonuniform distribution; grade 3, a few colors, nonuniform distribution; grade 4, many colors, nonuniform distribution; and grade 5, corneal surface partially exposed. Other methods of dry eye examination were also performed, including the cotton thread test, the Schirmer I test and modified Schirmer I test, measurement of tear film breakup time, scoring of corneal fluorescein staining density (grades 0 to 3) and area (grades 0 to 3), and rose bengal staining (grades 0 to 9). RESULTS: In 92 (84%) of 110 eyes, four or more of the five physicians agreed in their grade classifications. Among the 92 eyes, normal control eyes were classified into grades 1 and 2 (10 and 12 eyes, respectively) and dry eyes were classified into grades 2, 3, 4, and 5 (22, 26, 10, and 12 eyes, respectively). There was a significant correlation between the grading and the results of other dry eye examination modalities, including fluorescein staining, rose bengal staining, and tear film breakup time. CONCLUSIONS: Tear lipid layer interference patterns are highly correlated with dry eye severity.

Adolescent↗
PubMed1979

Bartter's syndrome--case report.

A 26-year-old female with Bartter's syndrome associated with Graves' disease is reported. This patient had a history of Graves' disease from the age of 22 and anti-thyroid drug (Methimazole) had been administered for 2 years. Thyroid function returned to normal but general fatigue and polyuria continued. Hypokalemia was diagnosed at 25 years of age and she was referred to our hospital for evaluation. Blood pressure was normal and laboratory data revealed normal thyroid function, hypokalemic alkalosis, high plasma renin activity and high plasma aldosterone concentration. She showed normal pressor sensitivity to norepinephrine infusion, grossly diminished pressor sensitivity to exogenous angiotensin II infusion compared with the normal. A renal biopsy specimen showed juxtaglomerular cell hyperplasia. Electron microscopy confirmed lacis cell (agranular cell) proliferation.

Adult↗