PubMed Health⌕ Search

Biomedical subjects

Y Tsutsui

Publications and source records attributed to Y Tsutsui.

At least 19 recordsLinked to original sources
PubMed2006

Differential expression of the immediate-early 2 and 3 proteins in developing mouse brains infected with murine cytomegalovirus.

Murine cytomegalovirus (MCMV) immediate-early (IE) 2 protein has been reported to be dispensable for growth and latency in mice. Therefore, its role in viral pathogenesis and tissue tropism is not known. Here we prepared specific antibodies to the IE2 and IE3 proteins by using fusion proteins expressed in Escherichia coli as antigens. Immunostaining of MCMV-infected cultured fibroblasts revealed IE2 protein to be expressed diffusely in the nucleoplasm similar to the IE1 protein. In contrast, expression of the IE3 protein, 88 kDa, exhibited a punctate pattern in the nucleus in the early phase of infection then diminished. In the brain of neonatal mice infected with MCMV, both IE2 and IE3 proteins were detected immunohistochemically in the cells of the ventricular walls early in infection. When the infection was prolonged, the IE2 protein was expressed in neurons of the cortex and hippocampus, while the IE3 protein was preferentially expressed in glial cells in the early phase of infection, and its levels declined during the infection. These results suggest that the IE2 protein may play a role in persistent infection in neurons, whereas the IE3 protein, expressed preferentially in glial cells, may play the main role in acute infection.

Animals↗
PubMed2001

A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle.

Pin2/TRF1 was independently identified as a telomeric DNA binding protein (TRF1) [1] and as a protein (Pin2) that can bind the mitotic kinase NIMA and suppress its ability to induce mitotic catastrophe [2, 3]. Pin2/TRF1 has been shown to bind telomeric DNA as a dimer [3-7] and to negatively regulate telomere length [8-11]. Interestingly, Pin2/TRF1 levels are regulated during the cell cycle, being increased in late G2 and mitosis and degraded as cells exit from mitosis [3]. Furthermore, overexpression of Pin2/TRF1 induces mitotic entry and then apoptosis [12]. This Pin2/TRF1 activity can be significantly potentiated by the microtubule-disrupting agent nocodazole [12] but is suppressed by phosphorylation of Pin2/TRF1 by ATM; this negative regulation is important for preventing apoptosis upon DNA damage [13]. These results suggest a role for Pin2/TRF1 in mitosis. However, nothing is known about how Pin2/TRF1 is involved in mitotic progression. Here, we describe a surprising physical interaction between Pin2/TRF1 and microtubules in a cell cycle-specific manner. Both expressed and endogenous Pin2/TRF1 proteins were localized to the mitotic spindle during mitosis. Furthermore, Pin2/TRF1 directly bound microtubules via its C-terminal domain. Moreover, Pin2/TRF1 also promoted microtubule polymerization in vitro. These results demonstrate for the first time a specific interaction between Pin2/TRF1 and microtubules in a mitosis-specific manner, and they suggest a new role for Pin2/TRF1 in modulating the function of microtubules during mitosis.

Binding Sites↗
PubMed2001

Items regarded as important for satisfaction in daily life by elderly residents in Kitakyushu, Japan.

The objective of this study was to determine what items were important for satisfaction in the daily life of elderly Japanese people living at home. The subjects consisted of 996 persons living in Yahatanishi Ward, Kitakyushu City, Japan, two percent of residents aged 60 years or over, who were randomly selected from the official register of voters. A questionnaire was sent to the subjects to determine their profiles and asking them to select the five items they considered most important for satisfaction in daily life from 35 predetermined items. The items with a significant difference using a chi 2 test between age groups, gender, place of residence, living conditions and level of disability were analyzed by logistic regression analysis. The top five items selected were "good health" (86%), "social security and pension" (47%), "self-care independence" (45%), "marital satisfaction" (34%), and a "good relationship with relatives" (33%). Logistic regression analysis showed gender, age group, living conditions, and level of disability significantly affected the preference for selection of 12 items. Men or younger persons regarded "health" and a "good relationship with a spouse" as very important, whereas women, older persons, or persons with a disability considered "self-care independence" and the "ability to walk" as important. The items selected for satisfaction in daily life and the order of preference yield important information about rehabilitative and social welfare services for elderly persons living at home.

Activities of Daily Living↗
PubMed2001

Activation of murine cytomegalovirus immediate-early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice.

Cytomegalovirus (CMV) is the most common infectious cause of congenital anomalies of the CNS in humans. We recently reported that the murine cytomegalovirus (MCMV) immediate-early (IE) gene promoter directs astrocyte-specific expression in adult transgenic mice. In the present study, we analyzed the activation of the MCMV IE promoter in developing transgenic mouse brains and compared the activation with that of the Musashi 1 (Msi1) gene, which is expressed in neural progenitor cells, including neural stem cells. During the early phase of neurogenesis, the transgene was expressed predominantly in endothelial cells of the vessels, but not in neuroepithelial cells in which Msi1 was expressed. During later stages of gestation, expression of the transgene was largely restricted to the ventricular zone (VZ) in the CNS, similar to the expression of Msi1. In neurosphere cultures from transgenic embryos in the late phase of neurogenesis, the transgene was expressed in some cells of neurospheres expressing Msi1 and nestin. In neural precursor cells induced to differentiate from stem cells, expression of the transgene was detected in glial progenitor cells, expressing GFAP, nestin, and Msi1, but not in cells expressing MAP2 or MAG. In postnatal development, persistent expression of the transgene was observed in astrocyte lineage cells as was Msi1. These spatiotemporal changes of the MCMV IE promoter activity during development of transgenic mice correlated with susceptible sites in congenital HCMV infection. Moreover, this transgenic mouse model may provide useful model for analysis of the regulation of the switching of neuronal and astrocyte differentiation, and the maintenance of the astrocyte lineage.

Animals↗
PubMed2001

Water drinking causes a biphasic change in blood composition in humans.

To investigate precisely the fluid shifts associated with water drinking in humans, we measured continuously blood density and plasma electrolyte concentrations using the mechanical oscillator technique and ion-selective electrodes, respectively, in healthy young volunteers before (10 min) and after (48 min) water drinking for a period of 2 min. Beat-by-beat blood pressure was also monitored throughout the experiment. Drinking 1 l tap water caused a transient increase in blood density immediately after the drinking episode (from 1051.1+/-0.5 g/l before drinking to 1051.8+/-0.5 g/l 4 min after the start of drinking, P<0.05), followed by a gradual reduction (1050.1+/-0.5 g/l at 31 min). This drinking-induced change paralleled those of haematocrit, plasma density and plasma volume. Plasma [Na+] and [Cl-] and osmolality decreased after drinking without transient increases and reached minima at about 30 min. A transient increase in mean arterial blood pressure was observed prior to the increase in blood density. These findings suggest that water drinking causes a biphasic change in plasma volume: initial haemoconcentration, probably due to sympathetic acceleration, followed by haemodilution due to the post-absorptive effect, and further suggest that the fluid shift associated with the initial haemoconcentration is isosmotic.

Adult↗
PubMed2001

An autopsy case of the schizophrenic 32 years after lobotomy.

An autopsy case is reported here of a 69-year-old patient with schizophrenia, who was known retrospectively to have had a prefrontal lobotomy 32 years previously. The patient was diagnosed as schizophrenic at the age of 24 and the lobotomy was undertaken 13 years later. The patient was recently found outside in a dehydrated condition and admitted to a general hospital, where he died of respiratory failure. Bilateral cystic lesions were found in the deep white matter of the frontal lobe. The cyst walls consisted of glial fibrous tissues, and severe demyelination with axonal destruction was diffusely observed in the white matter of the frontal lobe. In the thinner frontal cortex without arcuate fibers (U fibers) close to the cavities, cytoarchitectural abnormalities were observed. In the thalamic nuclei marked retrograde degeneration and astrocytic gliosis were observed. The detailed neuropathological findings of a lobotomized schizophrenic brain are reported here. It is proposed that one should be reminded of a lobotomized brain if bilateral cysts are found.

Aged↗
PubMed2001

Olfactory neuroblastoma with epithelial and endocrine differentiation transformed into ganglioneuroma after chemoradiotherapy.

We report a 56-year-old man in whom an olfactory neuroblastoma with epithelial and endocrine differentiation transformed into a mature ganglioneuroma after chemoradiotherapy. The tumor arising from the sphenoidal and maxillary sinuses showed rapid growth into the frontal lobe and metastasis to the cervical lymph nodes. The patient showed signs of a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). A radical craniofacial resection of the primary tumor was performed after 16 Gy of local irradiation and systemic chemotherapy. Three months after the operation, the patient died of mediastinal metastasis. The biopsy before chemoradiotherapy showed a neuroblastoma with Homer-Wright rosettes, fibrillary matrix, Flexner-Wintersteiner rosettes and antidiuretic hormone production. After chemoradiotherapy, the histology changed to that of a ganglioneuroma consisting of large ganglion cells and Schwann cells without immature neuroblastoma components. Although transformation to ganglioneuroma in an adrenal neuroblastoma is common, an olfactory neuroblastoma showing ganglioneuronal maturation after chemoradiotherapy has not been reported. The pluripotent progenitor cells of the olfactory neurons may be the origin and their existence explains why various neoplasms with neuronal and epithelial differentiation arise from the olfactory mucosa.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Multiple interactions among the components of the recombinational DNA repair system in Schizosaccharomyces pombe.

Schizosaccharomyces pombe Rhp55 and Rhp57 are RecA-like proteins involved in double-strand break (DSB) repair. Here we demonstrate that Rhp55 and Rhp57 proteins strongly interact in vivo, similar to Saccharomyces cerevisiae Rad55p and Rad57p. Mutations in the conserved ATP-binding/hydrolysis folds of both the Rhp55 and Rhp57 proteins impaired their function in DNA repair but not in cell proliferation. However, when combined, ATPase fold mutations in Rhp55p and Rhp57p resulted in severe defects of both functions, characteristic of the deletion mutants. Yeast two-hybrid analysis also revealed other multiple in vivo interactions among S. pombe proteins involved in recombinational DNA repair. Similar to S. cerevisiae Rad51p-Rad54p, S. pombe Rhp51p and Rhp54p were found to interact. Both putative Rad52 homologs in S. pombe, Rad22p and Rti1p, were found to interact with the C-terminal region of Rhp51 protein. Moreover, Rad22p and Rti1p exhibited mutual, as well as self-, interactions. In contrast to the S. cerevisiae interacting pair Rad51p-Rad55p, S. pombe Rhp51 protein strongly interacted with Rhp57 but not with Rhp55 protein. In addition, the Rti1 and Rad22 proteins were found to form a complex with the large subunit of S. pombe RPA. Our data provide compelling evidence that most, but not all, of the protein-protein interactions found in S. cerevisiae DSB repair are evolutionarily conserved.

Adenosine Triphosphatases↗
PubMed2000

Comparison of the mutational spectra of the lacZ transgene in four organs of the MutaMouse treated with benzo[a]pyrene: target organ specificity.

We recently demonstrated that not all organs with a high rate of induction of mutation in the lacZ transgene develop tumors in the lambdalacZ transgenic mice (MutaMouse) used for a long-term carcinogenicity study with benzo[a]pyrene (BP). To better understand the role of chemical-induced in vivo mutations in carcinogenesis, we compared the mutational spectra of the lacZ transgene in four organs of the MutaMouse obtained 2 weeks after five daily consecutive oral treatments with 125 mg/kg/day BP. lacZ transgenes were analyzed in two target organs (forestomach and spleen) and two non-target organs (colon and glandular stomach) for BP-induced carcinogenesis in MutaMouse, and all of these organs were highly mutated in the lacZ transgene. The sequence data showed similar mutational spectra of the lacZ transgene between the two target organs; the predominant mutations were G:C-->T:A transversions (55% and 50% for forestomach and spleen, respectively), followed by deletions (20% and 21% for forestomach and spleen, respectively) mainly at G:C site. The frequent G:C-->T:A transversions are consistent with reports of the mutational spectra produced in the p53 gene in tumors generated in rats and mice exposed to BP. In contrast, the mutational spectra of the lacZ transgene in the two non-target organs are different from those in the target organs, and are also suggested to differ from one another. These findings suggest an organ/tissue-specific mechanism of mutagenesis.

Administration, Oral↗
PubMed2000

Growth retardation and microcephaly induced in mice by placental infection with murine cytomegalovirus.

BACKGROUND: The placenta is regarded as a site of congenital cytomegalovirus (CMV) infection. The placental infection of fetuses with murine CMV (MCMV) was investigated in a mouse model. METHODS: The placentas and fetuses were examined using the polymerase chain reaction (PCR) and Southern blotting for viral DNA and immunostaining for viral antigen. Since the transplacental infection rarely occurs, the placentas were directly injected with MCMV at day 12.5 of gestation; the embryos were then allowed to develop until day 18.5 of gestation. RESULTS: Formation of infected foci at day 18. 5 of gestation was found in more than 60% of the injected placentas. Infection of about 50% of the embryos occurred from the infected placentas. The frequency of infection in the brain was 27%, which was the same as that in the liver and higher than that in the lungs. In the brains, infected cells were often observed in the ventricular zone of the cerebrum and sometimes in the cortical plate and the hippocampus. Developmental retardation with microcephaly was observed in about 25% of offspring exposed to infection in utero. CONCLUSIONS: These results suggest that formation of infected foci in the placenta is important for embryonic congenital infection, and that the cerebral ventricular zone is one of the most susceptible sites for CMV infection in the embryonic stage.

Animals↗
PubMed2000

Participation of the conjugated diene part for potent cytotoxicity of callystatin A, a spongean polyketide.

5-epi, 10-epi, 8-Deethyl, and 10-demethyl analogues of callystatin A, a potent cytotoxic spongean polyketide, were synthesized to elucidate structure-requirement for cytotoxic potency. Inversion of the asymmetric center at C-10 in callystatin A minimally affected the activity, while lack of the 10-methyl group in callystatin A decreased cytotoxicity. In addition, the C-5 epimer and the 8-deethyl analogue of callystatin A showed weaker cytotoxicity.

Animals↗
PubMed2000

Cytomegalovirus infection of the central nervous system stem cells from mouse embryo: a model for developmental brain disorders induced by cytomegalovirus.

Cytomegalovirus (CMV) is the most frequent infectious cause of developmental disorders of the central nervous system (CNS) in humans. Infection of the CNS stem cells seems to be primarily responsible for the generation of the brain abnormalities. In this study, we evaluated the infectivity of murine CMV (MCMV) in epidermal growth factor (EGF)-responsive CNS stem cells prepared from fetal mouse brains, and studied the effect of infection on growth and differentiation of the stem cells. The CNS stem cells were permissive for MCMV infection, although MCMV replication was slower than in mouse embryonic fibroblasts. MCMV infection inhibited the growth and DNA replication of the stem cells. A clonogenic assay revealed that MCMV infection suppressed generation of colonies from single stem cells. When uninfected stem cells were induced to differentiate, a decrease in expression of the primitive neuroepidermal marker nestin was observed by immunocytochemistry and flow cytometry, whereas expression of neurofilament and glial fibrillary acidic protein (GFAP) were induced. In virus-infected CNS stem cells, nestin expression was retained, whereas the expression of neurofilament was more severely inhibited than that of GFAP in these cells. Two-color flow cytometry showed that differentiated glial precursor cells were preferentially susceptible to MCMV infection. MCMV-infected and uninfected CNS stem cells were transplanted into the neonatal rat brains. The reduced number of infected stem cells were engulfed into the subventricular zone and expressed GFAP, but did not migrate further, in contrast to the uninfected stem cells. These results suggest that suppression of the growth of the CNS stem cells and inhibition of the neuronal differentiation by CMV infection may be primary causes of disorders of brain development in congenital CMV infection.

Animals↗
PubMed2000

Solitary squamous cell papilloma of the lung in a 40-year-old woman with recurrent laryngeal papillomatosis.

A rare case of recurrent respiratory papillomatosis (RRP) is reported with a review of the literature. A 40-year-old Japanese woman had suffered from RRP since 1 year of age. She developed a pulmonary squamous papilloma with a thin-walled cavity, which was suspected as being lung carcinoma. The trachea and bronchi around the tumor were intact, and no malignant transformation was present. Two types of human papillomavirus, 6 and 16, were detected, both in the laryngeal and pulmonary papillomas by in situ hybridization and the polymerase chain reaction method. To date, only 40 cases of juvenile laryngeal papilloma with pulmonary involvement have been reported in the English literature.

Adult↗
PubMed2000

Phosphoglyceride crystal deposition disease.

An extremely rare phosphoglyceride deposition disease is reported. A healthy 62-year-old Japanese woman suffered from tumors that repeatedly appeared in injured soft tissues for more than 20 years. No immunologic disorders or abnormal laboratory data were found. Histology showed foreign body granulomas consisting of macrophages surrounding yellowish-white crystals. The crystals were weakly positive by von Kossa's method, were dissolved in 30% acetic acid with gas, and were easily dissolved in 0.1 N NaOH or potassium hydroxide, losing their crystal structure. Using a scanning electron microscopy X-ray microanalyzer, phosphorus and calcium peaks were detected. Phosphoglycerides were detected by microscopic infrared spectrophotometry and microsampling mass spectrometry. The gold hydroxamic acid method for detecting phosphoglyceride showed strong positive staining in the crystals. Based on the above analyses, the deposited crystals were regarded as phosphoglyceride, which bound calcium as a counter ion. The crystals tended to be deposited at sites of injury, where macrophages had accumulated. The patient had received many injections of a medicine made from alcohol extract from bovine liver. We suspect that this medicine was related to the cause of the deposition as the deposition repeatedly appeared at the site of the injections.

Connective Tissue↗
PubMed2000

A recombination repair gene of Schizosaccharomyces pombe, rhp57, is a functional homolog of the Saccharomyces cerevisiae RAD57 gene and is phylogenetically related to the human XRCC3 gene.

To identify Schizosaccharomyces pombe genes involved in recombination repair, we identified seven mutants that were hypersensitive to both methyl methanesulfonate (MMS) and gamma-rays and that contained mutations that caused synthetic lethality when combined with a rad2 mutation. One of the mutants was used to clone the corresponding gene from a genomic library by complementation of the MMS-sensitive phenotype. The gene obtained encodes a protein of 354 amino acids whose sequence is 32% identical to that of the Rad57 protein of Saccharomyces cerevisiae. An rhp57 (RAD57 homolog of S. pombe) deletion strain was more sensitive to MMS, UV, and gamma-rays than the wild-type strain and showed a reduction in the frequency of mitotic homologous recombination. The MMS sensitivity was more severe at lower temperature and was suppressed by the presence of a multicopy plasmid bearing the rhp51 gene. An rhp51 rhp57 double mutant was as sensitive to UV and gamma-rays as an rhp51 single mutant, indicating that rhp51 function is epistatic to that of rhp57. These characteristics of the rhp57 mutants are very similar to those of S. cerevisiae rad57 mutants. Phylogenetic analysis suggests that Rhp57 and Rad57 are evolutionarily closest to human Xrcc3 of the RecA/Rad51 family of proteins.

Adenosine Triphosphatases↗
PubMed2000

Myoepithelial carcinoma of the lung arising from bronchial submucosa.

Myoepithelial neoplasm mainly occurs in the salivary glands and breasts and is extremely rare in the lung. To our knowledge, this report describes the first documented case of a myoepithelial carcinoma present in the lung. The tumor derived from the right main bronchial submucosa and exhibited a dual epithelial and smooth muscular phenotype by immunohistochemical and ultrastructural studies. It invaded the neighboring pulmonary tissue and the hilar lymph nodes. Despite a right pneumonectomy and chemotherapy, metastasis was found in the left lung 7 months later.

Bronchial Neoplasms↗
PubMed2000

Effects of genistein and synergistic action in combination with eicosapentaenoic acid on the growth of breast cancer cell lines.

Genistein, a prominent isoflavone in soy products, produced dose- and time-dependent in vitro growth inhibition at high concentrations (at least 185 microM) with an IC50 of 7.0-274.2 microM after 72 h incubation in four breast cancer cell lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line (HBL- 100) of human and animal origin; it stimulated estrogen-receptor-positive MCF-7 cells at low concentrations (3.7 nM-37 microM). Genistein-exposed cells underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub-G1 fraction in cell-cycle progression, and by a characteristic cell ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein, down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human breast cancer MCF-7 cells (genistein > 93.2 microM and EPA > 210.9 microM) and on MDA-MB-231 cells (genistein > 176.1 microM and EPA > 609.3 microM). Dietary intake of genistein in combination with EPA may be beneficial for breast cancer control.

Animals↗