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Biomedical subjects

Y Tsutsui

Publications and source records attributed to Y Tsutsui.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Murine cytomegalovirus for the animal models of congenital cytomegalovirus infection in human].

Cytomegalovirus(CMV) is the most common infectious cause of congenital anomalies of the central nervous system(CNS) caused by intrauterine infection in humans. Since studies of human subjects have obvious limitation and CMV have strict species specificity, we have developed model systems for brain abnormalities induced by infection of mouse embryos with murine CMV (MCMV) which has similarities in structure and biology to human CMV (HCMV). We have previously reported that brain abnormalities, such as microphthalmia and brain atrophy, can be induced in mouse embryo by injection MCMV in to the conceptus at mid gestation. We have also showed that neurotropic feature of MCMV are prominent and that viral antigens in neuronal cells are also observed for a prolonged time following infection. We showed the evidences which suggest that MCMV may persistently infect in neuronal cells, whereas lytic infection may preferentially occur in glial cell in the developing brain. Disturbance of the neuronal migration and loss of neurons were reported to occur postnatally in the brains of MCMV-infected mice. Furthermore, MCMV infection induces apoptosis in uninfected neurons, and blocks and induction of apoptosis of primary neuronal cultures. These viral effect on the induction and blocking neuronal apoptosis, resulting in persistent infection, may be important for pathogenesis of morphological and functional brain disorders caused by congenital CMV infection in humans.

Animals↗
PubMed1998

[Evaluation of factors associated with well-being of elderly in an aged society by analytic hierarchy process analysis].

In the coming aged society in Japan, where about one quarter of the citizens will be aged 65 or more, the social policy concerning the well-being of the elderly will become very important for the local government. In this analysis, the authors evaluated the importance of future social programs on this subject using the Analytic Hierarchy Process (AHP) technique in a community of Fukuoka prefecture. Fifty-three participants in this study regarded six keywords as important for the well being of the elderly in the coming aged society in the following order: health, family hobby life-long education, friends community, economic conditions, and social participation. Considering the contribution to each of the six keywords, composite priorities among the four programs were determined by the AHP technique to be in the following order: assistance for the social autonomy of the elderly, health promotion programs, development of welfare services, and development of medical services. These results indicate that for Japan to achieve a comfortable aged society, a democratic government made possible by autonomous individual citizen is desirable, with wide participation of individual in services provided by autonomous local governments that incorporate the structured elements shown to be important in this study.

Aged↗
PubMed1997

Identification of chiro-inositol and its formation by isomerization of myo-inositol during hydrolysis of glycosylphosphatidylinositol-anchored proteins.

myo-Inositol has been believed to be a sole inositol isomer existing in phosphatidylinositol (PI) and related derivatives. In this experiment, chiro-inositol, an inositol isomer other than myo-inositol, was identified in hydrolytic products from several GPI-anchored proteins. The chiro-inositol contents in several different GPI-anchored proteins including 5'-nucleotidase of bovine liver and alkaline phosphatase of mouse NS-1 varied with hydrolytic conditions of these GPI anchor. Isomerization of 20-60% of myo-inositol occurred on the hydrolysis in 6 N HCl solution. Under the hydrolytic conditions of a HCl gas stream in place of solution, however, isomerization was very low (less than 0.1%). Even in the hydrolysis under HCl gas stream, existence of CNBr accelerated the isomerization of inositol in GPI up to 70-95%. In the hydrolysis of phosphatidylinositol or myo-inositol 1-phosphate, however, a significant amount of chiro-inositol was not detected in 6 N HCl solution or in the existence of CNBr under the HCl stream. These facts indicated that isomerization occurred during the hydrolysis of the GPI anchor, when myo-inositol is substituted by glucosamine at 6-OH and is substituted by phosphate at 1-OH. It also suggested that the former identification of chiro-inositol in GPI structure in the various reports might be due to isomerization.

5'-Nucleotidase↗
PubMed1997

Disordered migration and loss of virus-infected neuronal cells in developing mouse brains infected with murine cytomegalovirus.

Microcephaly is the most prominent symptom of the developmental brain abnormalities induced by congenital cytomegalovirus (CMV) infection. To investigate the effect of CMV infection on neuronal migration in developing brains, mouse embryos on one side of uteri received, on day 15.5 of gestation (E15.5), an injection of murine CMV (MCMV) into the cerebral ventricles, and the embryos on the other side of the uteri were injected with minimum essential medium (MEM). Labeling with 5-bromo-2-deoxyuridine (BrdU) was accomplished by intraperitoneal injection of BrdU 6 h later. Disturbance of the neuronal migration and loss of neurons were observed postnatally in the brains of MCMV-infected mice, which were identified by immunohistochemical staining of viral antigen. Double staining of BrdU-labeled and viral antigen-positive cells in brains on the 7th postnatal day showed that the migration of BrdU-single-labeled cells, mainly localized in cerebral layers II-III, mostly preceded that of the viral antigen-positive cells. However, about 7.5% of the cells observed were double-labeled, especially in the layers III-IV, and a few double-stained cells were markedly disturbed in migration. In the brains of offspring labeled with BrdU 72 h after infection with MCMV on E15.5, most of the double-stained cells were seen around the ventricular and subventricular zones. These findings suggest that a disturbance of neuronal migration in addition to neuronal loss may play a crucial role in the development of microcephaly in congenital CMV infection in humans.

Animals↗
PubMed1997

Long-term continuous intravenous infusion of prostacyclin for severe primary pulmonary hypertension.

A patient suffering from severe symptomatic primary pulmonary hypertension (PPH) underwent long-term intravenous prostacyclin therapy; the first time for such treatment in Japan. A 26-year-old male had experienced gradually progressive dyspnea for about one year. Despite conventional therapy he suffered repeated syncopal attacks. However, after receiving a permanent central venous access device and a portable infusion pump, he recovered fully and was discharged. This remedy seems to be promising for PPH as has already been proven in Europe and North Americas, although in Japan it is not as yet commercially available and some problems still need to be resolved.

Adult↗
PubMed1997

[Disorders of neuronal migration in cerebral palsy].

We have analyzed 60 autopsy cases of cerebral palsy (CP) at the Aichi Prefectural Colony. The weight of the CP brains was distributed most frequently between 60 to 70% of normal brain weight. Coronal thin sections of the whole brains through the mammillary bodies were made using a large-sized miorotome and stained with hematoxylin-eosin (HE) and Klüver-Barerra (KB) stains. Macroscopically, CP brains were classified into microgyria-pachygyria type (45 cases), thin cerebral mantle type (10 cases), hydrocephalus type (3 cases), and lissencephalic type (2 cases). Macroscopic image analysis was performed using the KB-stained whole brain sections from the microgyria-pachygyria type CP brains, as well as 9 brains of control cases with non-neurological diseases and 4 brains with Fukuyama congenital muscular dystrophy (FCMD). The CP brains showed narrowed white matter with dilated ventricles compared with the controls. Microscopic analysis showed that ectopic grey matter (about 16%), and disorganization of the cerebral cortex (about 50%), and neuronal depletion (about 50%). These findings suggest that some of the CP brains resulted from disturbance of neuronal migration.

Adolescent↗
PubMed1997

Differential expression of the immediate-early and early antigens in neuronal and glial cells of developing mouse brains infected with murine cytomegalovirus.

Brain disorders induced by congenital cytomegalovirus (CMV) infection may appear at a later time after birth as a consequence of persistent infection and/or the activation of a latent infection of the neural cells. We have analyzed the infection dynamics of the neural cells in the neonatal mouse brains infected with murine CMV (MCMV) in the late stage of gestation. First we prepared a rat monoclonal antibody to the major immediate-early (IE)-89K antigen and then used the antibody for comparison of the expression of early and late viral genes in the developing mouse brains. The cells expressing the IE-89K antigen were mostly localized in the ventricular and subventricular zones and were preferentially double stained with anti-glial fibrillary acidic protein and anti-nestin antibodies. In contrast, the cells expressing the early nuclear antigen, detected by the monoclonal antibody D5, were diffusely distributed in the cortex and the hippocampus and were mostly double labeled with anti-neuron-specific enolase antibody. In neonatal mouse brains infected congenitally with recombinant MCMV, which expressed lacZ as a late gene, the number of the early nuclear antigen-positive cells was much higher than that of the beta-galactosidase-expressing cells, the number of which was almost the same as that of the IE-89K antigen-positive cells. In addition, the distribution of viral DNA-rich cells detected by DNA-DNA hybridization was similar to that of the IE-89K antigen-positive cells. These results suggest that CMV may persistently infect neuronal cells, whereas lytic infection may preferentially occur in the glial cells in the developing brain.

Aging↗
PubMed1997

[An analysis of factors associated with the increase of in-patient medical expenditures for the elderly in Fukuoka Prefecture].

In order to evaluate factors associated with the increase in the in-patient medical expenditures for the elderly in Fukuoka prefecture during the period from 1987 to 1991, an analysis was conducted based on the data of 10 Health Care Regions. According to the results, there were two patterns in the increase. The first was the pattern observed in the southern part of the prefecture, where most of the increase in the in-patient medical expenditures for the elderly was explained by the increase of medical expenditures per capita. Furthermore, this increase per capita was due to the increase in utilization rate. This pattern is considered to be associated with the increase of general hospital beds as well as with the increase of the dependent elderly in the regions. The second pattern was observed in urban regions, such as Fukuoka and Kitakyushu, where the increase of in-patient medical expenditures for the elderly was mainly due to the increase in the number of elderly in the regions. This pattern is considered to be associated with the increase in the population categorized as the aged household. The present result suggests that in order to control the medical expenditures for the elderly, different service-mix strategies will be necessary, respecting the socio-economic characteristics of each region.

Demography↗
PubMed1996

Mutagenicity of dihydroxybenzenes and dihydroxynaphthalenes for Ames Salmonella tester strains.

The mutagenicity of 3 dihydroxybenzene (DHB) and 9 dihydroxynaphthalene (DHN) isomers was examined by using 5 different Ames Salmonella mutagenicity tester strains in the presence and absence of phenobarbital and 5,6-benzoflavone-treated rat liver S9-mix. Of the 3 DHB isomers, 1,4-DHB (hydroquinone) was mutagenic, and of the 9 DHN isomers, 1,3-DHN (naphthoresorcinol), 1,4-DHN (hydronaphthoquinone), 1,6-DHN and 1,7-DHN were mutagenic. Mutagenicity of all the compounds tested was observed in the absence of S9-mix, while 1,4-DHN and 1,6-DHN were also mutagenic in the presence of S9-mix. The mutagenicity of 1,4-DHB and 1,4-DHN for TA104, which is a strain sensitive to oxidative mutagens, was almost completely or partially inhibited by superoxide dismutase (SOD) and/or catalase, indicating the involvement of activated oxygen species in mutagenesis. Furthermore, from the finding that the 4 DHNs were mutagenic for TA2637, the strain sensitive to frameshift mutagens, it is possible that the mutagenicity of DHNs for S. typhimurium was also attributable to DNA adducts that form with quinones and/or semiquinones through oxidation of DHNs. The mutagenicity of 1,3-DHN, which showed the largest number of revertants in strains TA100, TA98, TA2637 and TA104, was greatly decreased, when their pKM101 plasmid-deficient strains, TA1535, TA1538, TA1537 and TA2659 were used. This observation suggests that an SOS repair system was involved in the mutagenesis of 1,3-DHN for S. typhimurium.

Animals↗
PubMed1995

Prolonged infection of mouse brain neurons with murine cytomegalovirus after pre- and perinatal infection.

The susceptibility of mice at different developmental stages to a relatively low titer of cell culture-passaged murine cytomegalovirus (MCMV) infection was compared in terms of the urinary excretion of MCMV examined by plaque assay and in terms of the distribution of viral infection, determined by immunohistochemistry, using antibodies specific to the early nuclear antigen of MCMV. Viral infection on day 8.5 of gestation (E8.5) into the conceptus and intraperitoneal infection on day 15.5 of gestation (E15.5), postnatal day 2 (P2), postnatal day 11 (P11), and 30 days after birth (P30), respectively, were performed. Embryonal and perinatal mice were more susceptible to MCMV in terms of urinary excretion of the virus and the presence of viral antigen-positive cells in the brain, lungs, and kidneys. In the embryonal and perinatal infection, the viral antigen-positive cells in the neurons of the cerebral cortex and hippocampus were retained late after birth, even though the positive cells in the lungs and kidneys had disappeared. In the mice infected on E8.5, small clusters of viral antigen-positive cells were detected only in the cortex and hippocampus late after birth, without the urinary excretion of virus. These results suggest that when mice are infected with MCMV at the embryonal and perinatal stages, elimination of the infected neurons is delayed compared with that of the other cells in the lungs and kidneys. These findings provide a model for the analysis of pathogenesis of the subclinical congenital CMV infection that manifested clinically late after birth in humans as brain disorders.

Animals↗
PubMed1995

Mutagenicity of benzoquinones for Ames Salmonella tester strains.

The mutagenicity of 12 simple benzoquinone (BQ) derivatives was studied using five different Ames Salmonella mutagenicity tester strains in the presence and absence of S9 mix. Seven of the BQs used displayed mutagenicity with and/or without S9 mix, and most of them produced a marginal increase in revertants. p-Benzoquinone (p-BQ) showed the most potent mutagenic activity (17 induced revertants/nmol/plate for strain TA104 without S9 mix) among the BQs tested. TA104, which is sensitive to oxidative mutagens, was the most sensitive to the mutagenicity of the BQs of the five strains used, while the second most sensitive strain was TA2637, which detects bulky DNA adducts. Significant reductions in the mutagenicity of p-BQ, and 2,3-diCl-5,6-diCN-BQ without S9 mix were observed in the presence of catalase. These findings suggest that the mutagenicity of BQs for S. typhimurium is attributable to oxidative injury after BQ reduction and to DNA adducts that form with BQs that have electrophilic substituents.

Benzoquinones↗
PubMed1995

A novel allelic variant of serum amyloid A, SAA1 gamma: genomic evidence, evolution, frequency, and implication as a risk factor for reactive systemic AA-amyloidosis.

Reactive systemic amyloidosis, also called AA-amyloidosis is a rare fatal complication of common chronic inflammatory diseases such as rheumatoid arthritis. It has been proposed that as yet undefined factors other than persistent elevation of serum level of the precursor protein, serum amyloid A (SAA), are also important for the development of AA-amyloidosis. In this work we show genomic evidence for a novel allelic variant of human SAA, SAA1 gamma, which we have recently identified at the protein level. The SAA1 gamma [Ala52(GCC), Ala57(GCG)] differed from SAA1 alpha [Val52(GTC), Ala57(GCG)] only at one base, indicating a single point mutation. On the other hand, SAA1 beta [Ala52(GCC), Val57(GTG)] had not only one, but additional differences in a nearby intron and this portion was identical to the SAA2 gene, suggesting a crossing-over between the SAA1 and SAA2 genes. Furthermore, we report that there was a significant difference in the observed numbers of SAA1 alleles between rheumatoid arthritis patients with AA-amyloidosis and the control population (chi 2(2) = 11.59, p = 0.003) with a higher frequency of gamma-allele in the AA-amyloid group (0.70 vs. 0.37). There was also a notable difference in the distribution of SAA1 genotypes (chi 5(2) = 14.63, p = 0.012) with an increased frequency of gamma/gamma-homozygotes in the AA-amyloid group (0.60 vs. 0.18). Thus our findings indicate that this novel allelic variant may be an important risk factor for the development of AA-amyloidosis.

Adult↗
PubMed1995

Developmental disorders of the mouse brain induced by murine cytomegalovirus: animal models for congenital cytomegalovirus infection.

Developmental disorders induced by congenital cytomegalovirus (CMV) infection mainly involve the central nervous system. The type and degree of the brain disorders seems to depend on infection time during gestation, virulence, route of infection and viral susceptible cells in each embryonal stage. Since transplacental transmission has been reported not to occur with murine CMV (MCMV), we developed mouse models for congenital CMV infection by surgical injection of MCMV into the mouse conceptus or embryo at different gestational stages. For the early stage, the mouse embryos were not infected with MCMV even after injecting the virus into the blastocysts, which were developed in the pseudo-pregnant mothers or cultured in vitro. Isolated whole mouse embryos of day 7.5 of gestation (E7.5), adsorbed with a high titer of MCMV and cultured for 3 days, were susceptible to MCMV infection. Therefore, the mouse embryo acquires the susceptibility around this period. Microphthalmia and cerebral atrophy were induced in mouse embryos after injection of MCMV into the conceptus on E8.5. Viral antigen-positive cells were widely distributed in the mesenchyme around the oral and nasal cavities and in the mesenchyme around the brain, especially the endothelial cells of vessels and the perivascular mesodermal cells, then infection extends to the eyes, brain or choroid plexus. This finding suggests that mesenchymal infection may be the critical step in disrupting organogenesis, resulting in brain disorders. For the late stage, mouse embryos were infected with MCMV by injecting the virus into the cerebral ventricles on E15.5. Brains of the offspring showed massive necrosis with gliomesodermal proliferation in the cerebral cortex. Viral antigen-positive cells were observed in laminar array in the lesion-free cortex and the hippocampus, suggesting that the infected cells migrate in association with the lamina formation. Immunohistochemical double-staining showed that brain cells susceptible to MCMV infection may be mainly neuronal and endothelial cells, resulting in cerebral atrophy with reduction of neuronal cells and cystic lesions, presumably due to ischemic vascular changes.

Animals↗
PubMed1994

[Significance of a mass survey for colorectal cancer at the workplace].

Two thousand four hundred and forty workers from 2 plants were enrolled in a mass survey for colorectal cancer using a single immunological fecal occult blood test as screening. The occult blood test was positive in 71 (4.0%) out of 1,759 subjects in whom the test was conducted. A further investigation, including total colonoscopy or barium enema, was performed on 52 (73.2%) of the 71. Colon cancer was detected in 5 cases: 1 with advanced cancer and 4 with early cancer (cancer in the adenoma). The advanced cancer was successfully resected by surgery and the early cancers were removed by endoscopic polypectomy. Adenomas were found in 21 cases, 11 of which were polypectomized. From these results, it can be seen that a survey for colorectal cancer at the workplace is important, and by expanding the number of subjects for the survey in the workplace we can expect more and earlier detections of colorectal cancer.

Adenoma↗
PubMed1994

Facilitation of copulatory behavior by pCPA treatments following stria terminalis transection but not medial amygdala lesion in the male rat.

In this study, we examined the effect of p-chlorophenylalanine (pCPA), a serotonin synthesis inhibitor, on masculine sexual behavior in male rats following bilateral medial amygdala lesions (MAL) or bilateral stria terminals cuts (STC). Males with MAL and STC both showed a suppression of sexual behavior, compared to that of sham-operated males, when injected with saline. On the other hand, intraperitoneal injections of pCPA increased mount and intromission frequencies in males with STC. Although pCPA injections also slightly increased mount frequency in males with MAL, the injections failed to affect intromission behavior in MAL males. These suggest that the stria terminalis is insufficient as pathway of a whole output of the medial amygdala in regulating copulatory behavior. The medial amygdala may be involved in some other function, such as erection, than that of the stria terminalis.

Amygdala↗
PubMed1993

Immunohistochemical demonstration of neuron specific antigen, HPC-1 in the enteric nervous system of the guinea-pig distal colon.

The HPC-1 antigen is a newly identified neuron specific membrane protein in the central nervous system. The HPC-1 antigen was revealed similarity to epimorphin. The presence of HPC-1 antigen in the enteric nervous system of guinea-pig distal colon was immunohistochemically demonstrated using the antibody against the HPC-1. Immunohistochemical study clearly revealed the topography and structure of the enteric nervous system of the guinea-pig distal colon. HPC-1 was present only in the nervous system and entirely distributed. HPC-1 antigen is present at the surfaces of ganglion cells, but not in the cytoplasm.

Animals↗