Biomedical subjects

Yuko Saito

Publications and source records attributed to Yuko Saito.

At least 37 records · Page 2Linked to original sources

PubMed2004

Possible involvement of CS-ACS1 and ethylene in auxin-induced peg formation of cucumber seedlings.

BACKGROUND AND AIMS: Cucumber (Cucumis sativus) seedlings develop a peg on the concave side of the gravitropically bending transition zone between the hypocotyl and the root after seed germination. Peg initiation occurs in response to auxin when its levels in the concave side of the transition zone exceed a particular threshold through the graviresponse. Ethylene also plays an important role in peg formation, but its relationship to auxin in this event is not understood. Here, the role ethylene plays in auxin-induced peg formation is studied. METHODS: Peg formation of cucumber seedlings exposed to ethylene at different stages of growth or during exogenous auxin treatment was observed. In addition, ethylene evolution from the concave and convex sides of the transition zone was compared and their transcription of CS-ACS (1-aminocyclopropane-1-carboxylic acid synthase) genes was analysed by RT-PCR and in situ hybridization. KEY RESULTS: Seedlings treated with ethylene after peg initiation produced an enlarged peg, whereas ethylene treatment before peg initiation inhibited peg formation. Ethylene also promoted the development of the peg in the auxin-treated seedlings. Furthermore, the concave side of the transition zone at peg initiation produced more ethylene and CS-ACS1 mRNA than the convex side. CONCLUSIONS: Since CS-ACS1 is an auxin-inducible gene, the greater abundance of auxin in the concave side of the transition zone causes peg initiation and increases CS-ACS1-mediated ethylene biosynthesis, which then facilitates peg development.

Amino Acids, Cyclic↗

PubMed2004

Association of estrogen receptor alpha gene polymorphisms with neurofibrillary tangles.

Estrogen receptor alpha (ERalpha) may be implicated in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to clarify the association between ERalpha gene polymorphisms and AD-related pathologic changes. The staging of neurofibrillary tangles (NFT) and senile plaques (SP) was performed according to the method by Braak and Braak and two polymorphisms, PvuII (P or p) and XbaI (X or x), of the ERalpha gene were typed in 551 Japanese cadavers (294 men and 257 women; mean age, 80.8 years). Distributions of the NFT and SP stages significantly correlated with age (NFT: r = 0.306, p < 0.0001; SP: r = 0.237, p < 0.0001) and were significantly higher in patients with the apolipoprotein E epsilon4 allele (p < 0.0001). Possession of the P allele showed a trend to be associated with a more serious NFT stage, but had no relationship with the SP stage. In men, a significant association between PvuII polymorphism and the NFT stage (p = 0.002) was found, revealing a gene- dose effect of the P allele. Similar results were obtained in the men without the epsilon4 allele (p = 0.011). Multiple regression analyses demonstrated that age was the strongest determinant of the NFT stage, possession of the epsilon4 allele was the next strongest, and PvuII polymorphism was the third strongest (p < 0.0001, R(2) = 0.144). The XbaI polymorphism did affect neither the NFT stage nor the SP stage. In conclusion, the PvuII polymorphism of the ERalpha gene is associated with Braak NFT stages and possession of the P allele may act as a risk factor for AD in Japanese men, especially in those without the epsilon4 allele.

Aged↗

PubMed2004

In situ detection of apolipoprotein E epsilon 4 in archival human brain.

A monoclonal antibody specific to apolipoprotein E 4 (apoE4) was applied immunohistochemically to archival human brain tissue. The examined 30 cases comprised four epsilon/epsilon4, 10 epsilon3/epsilon4, one epsilon2/epsilon4, 10 epsilon3/epsilon3 and five epsilon2/epsilon3 genotypes. The anti apoE4 antibody visualized senile plaques, neurofibrillary tangles and reactive astrocytes, as well as serum in the blood vessels and vascular smooth muscle cells in the cases of epsilon4. Moreover, the staining intensity was stronger in the cases carrying the epsilon4 homozygosity than in those cases of epsilon4 heterozygosity. Specific immunoreactivity was not obtained in those cases not carrying the epsilon4 allele. This method will allow in situ detection of apoE epsilon4 and contribute to studies of the effect of epsilon4 on Alzheimer's disease.

Alleles↗

PubMed2004

Isolation of cucumber CsARF cDNAs and expression of the corresponding mRNAs during gravity-regulated morphogenesis of cucumber seedlings.

Cucumber seedlings show positive gravitropism and bend in the transition zone between the hypocotyl and the root. The peg, a specialized protuberance, develops on the concave side of the bending transition zone. Auxin and the mRNA of an auxin-inducible gene (CsIAA1) isolated from cucumber are differentially accumulated across the transition zone during the gravity-regulated peg formation. In this study, five cDNAs of Auxin Response Factors (ARFs) from cucumber were isolated and their mRNA accumulation was compared with that of CsIAA1. The tissue specificity of CsARF2 mRNA accumulation was similar to that of CsIAA1. Because the structural character of CsARF2 predicts that it is a transcriptional activator, CsARF2 may be involved in the activation of CsIAA1 transcription, which plays a role in gravity-regulated peg formation. Neither gravity nor auxin affected mRNA accumulation of five CsARFs including CsARF2, suggesting that CsARF2 may be regulated at a post-transcriptional level to induce the asymmetric expression of the CsIAA1 gene in response to gravistimulation and auxin in cucumber seedlings.

Amino Acid Sequence↗

PubMed2004

Determination of 1-deoxynojirimycin in mulberry leaves using hydrophilic interaction chromatography with evaporative light scattering detection.

A simple and rapid method for determining 1-deoxynojirimycin (DNJ), a potent glucosidase inihibitor present in mulberry leaves (Morus alba and Morus bombysis), by high-performance liquid chromatography coupled to an evaporative light scattering detector (ELSD) has been developed. DNJ was separated from an extract of mulberry leaves on a TSKgel Amide-80 column, which is a representative column for hydrophilic interaction chromatography. During postcolumn detection, DNJ was detected by ELSD and concurrently identified by mass spectrometry. The detection limit was 100 ng. This method is sufficiently sensitive for determining DNJ in mulberry leaves and other related products.

1-Deoxynojirimycin↗

PubMed2004

Increased expression of neuronal cyclooxygenase-2 in the hippocampus in amyotrophic lateral sclerosis both with and without dementia.

The pathophysiological basis of cognitive dysfunction, including frontotemporal dementia (FTD), in patients with amyotrophic lateral sclerosis (ALS) and ALS with dementia (ALSD) remains unclear. On the other hand, increased expression of cyclooxygenase-2 (COX-2) in the spinal cord is thought to play a pivotal role in motor neuron degeneration in ALS. In this study, to assess the relationship between the neuronal COX-2 expression in the cerebrum, the formation of tau- and alpha-synuclein-negative but ubiquitin-positive neuronal inclusions (UPIs), and dementia in motor neuron disease (MND), we examined neuronal COX-2 immunoreactivity in the frontal cortex and hippocampus of patients with non-demented ALS without UPIs ( n=11), ALSD with UPIs ( n=6), and normal controls ( n=24) using a quantitative immunohistochemical technique. Neuronal COX-2 expression in all CA1-4 in the hippocampus was significantly up-regulated in the ALSD group, and, to lesser degree but significantly, in the ALS group. Neuronal COX-2 expression in the frontal cortex was also significantly up-regulated in the ALSD group but not in the ALS group. These findings suggest that (1) the frontal cortex and hippocampus of MND are involved in the same pathogenic process associated with COX-2 induction that has been observed in spinal anterior horn cells, (2) COX-2 induction in the cerebrum is a pathogenic process that can occur even in the absence of UPI formation in MND, and (3) COX-2 expression in the cerebrum may be associated with cognitive dysfunction in MND.

Aged↗

PubMed2004

Simple and rapid determination of 1-deoxynojirimycin in mulberry leaves.

A simple and rapid method for determining 1-deoxynojirimycin (DNJ), a potent glucosidase inhibitor present in mulberry leaves (Morus alba and Morus bombysis), by high performance liquid chromatography coupled to an evaporative light scattering detector (ELSD) has been developed. DNJ was separated from extract of mulberry leaves on TSK gel Amide-80 column, which is a representative column for hydrophilic interaction chromatography. During post column detection, DNJ was detected by ELSD and concurrently identified by mass spectrometry. The detection limit was 100 ng. This method is sufficiently sensitive for determining DNJ in mulberry leaves and other related products.

1-Deoxynojirimycin↗

PubMed2004

Neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, in the hippocampus of patients with schizophrenia.

Several types of evidence suggesting that the inflammatory response system is associated with pathophysiology of schizophrenia have been accumulated. Recently, a prospective double-blind study demonstrated that supplementary treatment with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, produced significantly greater improvement in scores on the Positive and Negative Syndrome Scale (PANSS) and on all subscales during the acute phase in patients with schizophrenia compared with risperidone alone therapy. The therapeutic effect of celecoxib on the psychopathology of schizophrenia is speculated to be based on COX activity inhibition; however, the detailed pharmacological mechanisms are unclear. To clarify whether or not COX-2 expression is altered in schizophrenia, we examined neuronal COX-2 expression in the hippocampus from cases of schizophrenia (n = 17), normal controls (n = 22), and cases of Alzheimer's disease (AD) as a positive control (n = 17). Quantitative immunohistochemical analysis demonstrated that neuronal COX-2 expression was significantly up-regulated in each CA1-4 region in Alzheimer's disease compared with controls, and that the mean COX-2 immunointensity in CA1-4 was significantly correlated with Abeta load in cases of Alzheimer's disease. In contrast, COX-2 expression was not up-regulated in any subdivision of the hippocampus in the schizophrenia group. These results suggest that celecoxib may affect the pathophysiology of schizophrenia through COX-2-independent actions rather than by inhibiting activity of up-regulated COX-2 protein.

Aged↗

PubMed2004

Aberrant phosphorylation of alpha-synuclein in human Niemann-Pick type C1 disease.

Niemann-Pick type C1 disease (NPC1) is an autosomal recessive neurovisceral storage disease caused by the mutation of NPC1 gene, resulting in perturbed intracellular transport of unesterified cholesterol. In NPC1, early-onset tauopathy is a constant feature. In addition, in NPC1 patients with ApoE epsilon4 homozygosity, deposition of A beta occurs mimicking Alzheimer disease (AD). Since AD is frequently associated with neuronal expression of alpha-synuclein, we investigated phosphorylated alpha-synuclein (psyn) immunoreactivity in the brains of 12 NPC1 patients, ages at death ranging from 9 months to 55 years. Psyn immunoreactivity was demonstrated in the perikarya of storage neurons and oligodendroglia in 10 cases. The immunoreactivity appeared more intense in subjects who had the ApoE epsilon4 allele. Lewy bodies were found in the substantia nigra in 2 of these cases. The psyn immunoreactivity was most intense in the substantia nigra where tauopathy was most severe. Phosphorylated tau and alpha-synuclein frequently colocalized. This study first documents alpha-synucleinopathy in NPC1. This observation suggests that the defect in intracellular cholesterol trafficking in NPC1 may provoke aberrant phosphorylation of alpha-synuclein and tau, and that this phosphorylation is enhanced by the ApoE epsilon4 allele. Thus, elucidation of metabolic pathways in NPC1 could provide clues to common mechanisms associated with neurodegeneration.

Adolescent↗

PubMed2004

Lewy body-related alpha-synucleinopathy in aging.

To clarify the significance of Lewy body (LB)-related alpha-synucleinopathy in aging, we investigated the incidence of LBs in 1,241 consecutive autopsy cases (663 males and 578 females). LB pathology was identified histologically in sections stained with hematoxylin and eosin and with anti-ubiquitin and anti-alpha-synuclein antibodies. Cases without LBs were classified as LB stage 0 (987 cases). Cases with LBs were classified as follows: LB stage I = incidental LBs (149 cases); LB stage II = LB-related degeneration without attributable clinical symptoms (47 cases); LB stage III = Parkinson disease without dementia (10 cases); LB stage IV = dementia with Lewy bodies (DLB) transitional (limbic) form (25 cases); and LB stage V = DLB neocortical form (23 cases). The average age at death was greater for those cases with LBs. There were no gender differences in the LB pathology. G842A polymorphism in the paraoxonase I gene was associated with men in LB stage II or above and suggests a gender-specific risk factor. LB stage V had higher stages of neurofibrillary tangle and senile plaque involvement and also had a higher frequency of apolipoprotein E epsilon4. Our findings indicate that LBs are associated with cognitive decline, either independently or synergistically with neurofibrillary tangles and senile plaques.

Age Factors↗

PubMed2004

Staging of argyrophilic grains: an age-associated tauopathy.

We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains. Here we analyzed 1,405 serial autopsy cases from 2 hospitals and detected AGs only in cases older than 56 years of age. The distribution of AGs followed a stereotypic regional pattern. Thus, we propose the following staging paradigm: stage I: AGs restricted to the ambient gyrus and its vicinity; stage II: AGs more apparent in the anterior and posterior medial temporal lobe, including the temporal pole, as well as the subiculum and entorhinal cortex; and stage III: abundant AGs in the septum, insular cortex, and anterior cingulate gyrus, accompanying spongy degeneration of the ambient gyrus. Sixty-three of 65 (96.9%) argyrophilic grain stage III cases without other dementing pathology were classified as 0.5 or higher in the clinical dementia rating. Forty-seven of 50 dementia with grains cases (94%) were stage III and 3 were stage II. No association with apoE genotyping was detected. Our study further confirms that dementia with grains is an age-associated tauopathy with relatively uniform distribution and may independently contribute to cognitive decline in the elderly.

Adult↗

PubMed2004

Granulomatous meningitis as a late complication of iodized oil myelography.

The present report is an autopsy case of an 83 year old man with severe kyphoscoliosis and granulomatous meningitis as a late complication of iodized oil myelography. He suffered from mild cognitive impairment and died of pneumonia. At autopsy, the brain showed yellow-brown granular material on its surface, mainly in the Sylvian fissure. Microscopically, granulation tissue was seen around areas of ossification encasing the foreign material. Iodized oil apparently changed into two types of foreign bodies: eosinophilic membranous lipodystrophy-like features and homogenous yellow crystals of various sizes. The pathology was identical to foreign-body granulomatous meningitis, caused by iodized oil myelography, and caused cognitive impairment in this patient.

Aged↗

PubMed2004

Neuropathological diagnostic criteria for Alzheimer's disease.

Neuropathological diagnostic criteria for Alzheimer's disease (AD) are based on tau-related pathology: NFT or neuritic plaques (NP). The Consortium to Establish a Registry for Alzheimer's disease (CERAD) criterion evaluates the highest density of neocortical NP from 0 (none) to C (abundant). Clinical documentation of dementia and NP stage A in younger cases, B in young old cases and C in older cases fulfils the criterion of AD. The CERAD criterion is most frequently used in clinical outcome studies because of its inclusion of clinical information. Braak and Braak's criterion evaluates the density and distribution of NFT and classifies them into: I/II, entorhinal; III/IV, limbic; and V/VI, neocortical stage. These three stages correspond to normal cognition, cognitive impairment and dementia, respectively. As Braak's criterion is based on morphological evaluation of the brain alone, this criterion is usually adopted in the research setting. The National Institute for Aging and Ronald and Nancy Reagan Institute of the Alzheimer's Association criterion combines these two criteria and categorizes cases into NFT V/VI and NP C, NFT III/IV and NP B, and NFT I/II and NP A, corresponding to high, middle and low probability of AD, respectively. As most AD cases in the aged population are categorized into Braak tangle stage IV and CERAD stage C, the usefulness of this criterion has not yet been determined. The combination of Braak's NFT stage equal to or above IV and Braak's senile plaque Stage C provides, arguably, the highest sensitivity and specificity. In future, the criteria should include in vivo dynamic neuropathological data, including 3D MRI, PET scan and CSF biomarkers, as well as more sensitive and specific immunohistochemical and immunochemical grading of AD.

Aged↗

PubMed2004

[Parkinson disease with dementia--responsible locus for dementia].

Responsible locus for dementia in Parkinson disease (PD) was investigated. Serial 1,395 autopsy cases were studied for the combined pathology of PD and Alzheimer disease (AD). Following the one-year rule by the first Consensus Guidelines, definite AD pathology was quite rare in PD with dementia (PDD) but common in dementia with Lewy bodies (DLB) . Plaque-dominant senile changes apparently enhanced neocortical Lewy-body pathology in both the conditions. About the hypometabolism in the visual cortex of PDD, a 66-year old man presented with fluctuation in hallucination commensurate with fluctuating hypometabolism. Considering the paucity in pathological changes of the visual cortex, this hypometabolism may represent functional impairment in the fiber connection. Comparative pathological studies with PD and PDD were carried out. Only one case of a 48-year-old woman, who unexpectedly died of heart failure, was free from cognitive decline, and did not show limbic and neocortical involvement. Another case of a 75-year old man with MCI presented with the similar pathology. All other cases showed clinical documentation of cognitive impairment and limbic and neocortical pathological involvement. Thus, the combination of prospective clinical and radiological studies and retrospective pathological studies (dynamic neuropathology) may be essential to investigate a role of the basal-forebrain cholinergic system.

Aged↗

PubMed2003

Mapping of genetic modifiers of thymic lymphoma development in p53-knockout mice.

The strain dependency of the spectrum and latency of tumors has been reported in p53-deficient (KO) mice, suggesting the presence of modifiers for the outcome of the p53 deficiency. The modifiers provide clues to the oncogenic pathway in cells lacking p53, the most frequently mutated gene in a wide variety of human cancers. To search the modifiers, we induced 160 lymphomas and 69 skin tumors by gamma-irradiation of p53(KO/+) backcross mice between BALB/c and MSM strains and performed genome scan. BALB/c-derived alleles at three loci on chromosome 19, Mp53D1 (modifier of p53-deficiency) at D19Mit5, Mp53D2 at D19Mit90 and Mp53D3 at D19Mit123, extended the latency of thymic lymphoma development (P values in Mantel-Cox test were 0.0007, 0.0007 and 0.0003, respectively). Mp53D3 also increased the latency of skin tumors (P value, 0.0008). The linkage of Mp53D2 was confirmed by the experiment using 94 p53-KO mice consomic for chromosome 19, providing a significant linkage. However, the linkage was not confirmed for Mp53D1 or Mp53D3, suggesting epistasis of genes involved in the tumorigenesis.

Alleles↗

PubMed2003

Accumulation of phosphorylated alpha-synuclein in aging human brain.

Alpha-synuclein in Lewy bodies (LBs) is phosphorylated at Ser129. We raised monoclonal and polyclonal antibodies to this phosphorylation site (psyn) and examined 157 serial autopsy brains from a geriatric hospital. Anti-psyn immunoreactivity was observed in 40 of these cases (25.5%). Immunohistochemistry revealed 4 novel types of pathology: diffuse neuronal cytoplasmic staining (pre-LB); neuropil thread-like structures (Lewy threads); dot-like structures similar to argyrophilic grains (Lewy dots); and axons in the white matter (Lewy axons). This novel pathology was abundantly present around LBs and also involved the limbic subcortical white matter, the cerebral cortical molecular layer, and the spongiform changes of the medial temporal lobe associated with cases of dementia with LBs (DLB). The phosphorylated alpha-synuclein was limited to the temporal lobe in cases of Parkinson disease, spread from the temporal lobe to the frontal lobe in cases of DLB transitional form and further spread to the parietal and occipital lobes in DLB neocortical form. Our findings suggest that LB-related pathology initially involves the neuronal perikarya, dendrites, and axons, causes impairment of axonal transport and synaptic transmission, and later leads to the formation of LBs, a hallmark of functional disturbance long before neuronal cell death.

Aged↗

PubMed2003

[Marked decrease of intracranial atherosclerosis in contrast with unchanged coronary artery stenosis in Japan].

We conducted comparative studies on intracranial atherosclerosis and coronary artery stenosis over the past 28 years. Two-year consecutive autopsy case studies from an urban geriatric hospital between 1974-1975 (Group I. 484 cases). 1986-1987 (Group II, 504 cases) and 2000-2001 (Group III, 273 cases) were employed. Atherosclerotic changes of the bilateral middle cerebral arteries and basilar artery were semiquantitatively evaluated as none (0), mild (1), moderate (2) and severe (3) and values of the 3 arteries were totalled to give a value of 0-9 which was taken as the intracranial atherosclerotic index (ICAI). The coronary stenotic index was calculated as previously reported (Sugiura et al 1969). ICAI and CSI were directly compared with each other, together with risk factors for each, including mean blood pressure (BP), serum level of total cholesterol (Tch) and the history of diabetes mellitus (DM+). Chronologically ICAI decreased dramatically but CSI did not change at all. There was continuous lowering of BP, elevation of Tch and increased incidence of DM+. There was a significant positive correlation in BP in relation to both ICAI and CSI (p < 0.01). DM+ vs. CSI (p < 0.01) and ICAI (p < 0.05), and Tch vs. CSI (p < 0.01) but not ICAI. Regression analysis highlighted age and BP as major risk factors for ICAI. Our study provides the first morphological confirmation of marked decrease of the intracranial atherosclerosis in the recent 28 years, in contrast with unchanged coronary stenosis in Japanese elderly subjects.

Aged↗

PubMed2003

[Epidemic study of pet allergy in Wakayama Prefecture].

In Japan, the number of households who have pets has gradually increased, together with the number of people who have pet allergies. Many reports exist on pollen and mite allergy, but few on pet allergy. We conducted an epidemic study in 531 first-year junior high school students in Wakayama prefecture in 1999. Questionnaires covered allergy and measurement of total IgE antibody using CAP system (Pharmacia Co. Ltd.) and specific IgE antibody using MAST26 system (Hitachi chemical Co. Ltd.). Of 306 students having pets, 11 were allergic to dogs, 11 to cats, 8 to both, and 1 to rabbits. Clinical symptoms were various. No differences in symptoms were observed among allergens. Serum total IgE tended to increase in students who suffered from pet allergies. Positive rates of specific IgE antibodies were high in mites and Japanese cedar pollen (36.7% for mites and 37.0% for Japanese cedar pollen), and also in dogs and cats (15.4% for dogs and 18.2% for cats). Specific dog and cat IgE antibodies increased significantly (p = 0.033 for dog and for p < 0.0001 cat), but no significant correlation was found between the positive specific IgE antibody and history of pet keeping.

Adolescent↗