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Biomedical subjects

Yuko Saito

Publications and source records attributed to Yuko Saito.

11 recordsLinked to original sources
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↗
PubMed2002

Severe involvement of the ambient gyrus in a case of dementia with argyrophilic grain disease.

We report here the severe involvement of the ambient gyrus in a case of argyrophilic grain (AG) dementia (AGD). The patient was a 78-year-old man who was first presented with prosopagnosia (agnosia of the face) at age 68, which was followed by progressive mental decline and the patient's death in a state of tetraplegia. The postmortem study showed severe atrophy of the medial temporal lobe with anterior gradient, most prominent in the ambient gyrus. Histologically, numerous AGs, pretangles and coiled bodies were detected by Gallyas-Braak (G-B) silver staining and also by immunostaining with various anti-tau antibodies in the affected area. Tau-immunoreactive ballooned neurons were also present. Neuronal loss and gliosis with laminar sponginess were evident in the ambient gyrus. Diffuse plaques were seen in the neocortex and frequently associated with clusters of AGs, which were morphologically distinct from neuritic plaques. Neurofibrillary tangles were localized in the entorhinal area. Vascular lesions were very scanty. Thus, this case fulfilled the morphological criteria of AGD. It is still unclear whether AG itself causes neuronal degeneration leading to dementia. The present case may reflect the importance of the ambient gyrus in the center of neuronal degeneration in AGD.

Aged↗
PubMed2002

Niemann-Pick type C disease: accelerated neurofibrillary tangle formation and amyloid beta deposition associated with apolipoprotein E epsilon 4 homozygosity.

Niemann-Pick type C disease is a neurovisceral storage disorder. Neurofibrillary tangles similar to those in Alzheimer's disease have been reported in most juvenile/adult patients without amyloid beta protein (Abeta) deposits. Recently, we found deposits of Abeta in the form of diffuse plaques in three (31- and 32-year-old sisters and a 37-year-old man) of nine Niemann-Pick type C disease patients, who presented with most severe tauopathy and with numerous neurofibrillary tangles. Abeta deposits were not detected in any of the control brains of patients younger than age 42 years. These three patients with Abeta deposit all were homozygotes of apolipoprotein E epsilon 4. Our study suggested that NPC1 gene mutations combined with homozygosity of apolipoprotein E epsilon 4 alleles could manifest neuropathology similar to that of Alzheimer's disease. Investigation of these patients may provide an important clue for understanding the pathogenesis of Alzheimer's disease.

Adult↗
PubMed2002

Severe involvement of ambient gyrus in dementia with grains.

Argyrophilic grains are detected as punctate or filiform structures in the neuropil of the medial temporal lobe, and dementia with grains (DG) is defined as a form of dementia with argyrophilic grains as the only explainable cause. We found argyrophilic grains in 43.2% of our 190 serial autopsy brains (mean age, 79.7 yr) from a community-based geriatric hospital, but only 20% of these argyrophilic grain-positive brains fulfilled the criteria for DG. To determine if there are structural differences between cognitively normal cases with argyrophilic grains (CNG) and DG, we studied 14 brains with CNG and 15 brains with DG. All cases of DG had severe atrophy of the ambient gyrus (the junction between temporal lobe and amygdala) with spongiosis, neuronal loss, and gliosis, as well as many grains, pretangles, coiled bodies, and tau-immunoreactive astrocytes. Comparable changes were not present in the ambient gyrus of CNG brains. The temporal neocortex and hippocampus were relatively spared in DG, in contrast to Alzheimer disease. Our study suggests that selective severe involvement of the ambient gyrus may explain the clinical manifestations of a limbic-type dementia in DG.

Aged↗
PubMed2002

[2001 survey of pollen in Wakayama City with a real-time pollen counter].

Self-care is gradually being recognized as important in the treatment of pollinosis, based up to now on data on airborne pollen. To determine the real-time numbers of airborne pollen would be more useful in self-care, however, so we studied the usefulness of the real-time pollen counter. Between Feb. 2, 2001, and Apr. 26, 2001, 4 types of airborne pollen i.e., Japanese cedar, Japanese cypress, black alder, and beech observed in Wakayama City were counted with a Durham pollen counter and a real-time pollen counter (Yamato Manufacturing Co. Ltd.). Correlation between the 2 pollen counters was r = 0.69 for Japanese cedar in March and r = 0.89 for Japanese cypress in April. A high correlation was observed between outcomes of the 2 pollen counters. The amount of pollen from black alder and beech was less than that from Japanese cedar and cypress. Unexpected peaks were observed not related to the pollen number is apparently due to snow. We have taken measure against snow, so we concluded that the real-time pollen counter was useful in counting the amount of airborne pollen over time.

Air Pollutants↗