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Biomedical subjects

Y Fukazawa

Publications and source records attributed to Y Fukazawa.

At least 19 recordsLinked to original sources
PubMed2001

Effects of proteasome inhibitors on the synaptic localization of Vesl-1S/Homer-1a proteins.

The Vesl-1S/Homer-1a proteins are upregulated during seizure and long-term potentiation, but are rapidly degraded by ubiquitin-proteasome systems under normal conditions. We examined the distribution of Vesl-1S proteins in cultured hippocampal neurons. Application of proteasome inhibitors caused accumulation of Vesl-1S immunoreactivity in the neurons which showed a punctate distribution in the cortical regions of the cells, and these puncta were found to be juxtaposed with synaptophysin, a presynaptic, synapse-specific protein. These results suggest that Vesl-1S protein is synaptically targeted.

Acetylcysteine↗
PubMed2001

Phorbol esters promote postsynaptic accumulation of Vesl-1S/Homer-1a protein.

We examined effects of phorbol esters on the amount and the subcellular distribution of the activity-regulated protein Vesl-1S/Homer-1a in cultured hippocampal neurons. Major Vesl-1S immunoreactivity (IR) was detected throughout neuronal somata under control conditions. Bath application of phorbol esters, PMA and PDBu resulted in the increase in the amount of Vesl-1S proteins and promoted punctate distribution of Vesl-1S IR at the cortical regions of the neuronal somata. Immunofluorescent observations using antisynaptophysin and anti-Vesl-1S antibodies, and electron microscopic observations, revealed that Vesl-1S accumulated at postsynaptic regions following PMA application. Membrane depolarization with high concentrations of external potassium also promoted the punctate distribution of Vesl-1S IR. These results demonstrate that phorbol-triggered reaction cascades result in the accumulation of Vesl-1S protein at postsynaptic regions, and suggest that these phorbol effects may mimic those caused by synaptic activities.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

Cloning and characterization of a novel serine/threonine protein kinase gene expressed predominantly in developing brain.

We have isolated a rat gene, sbk, that encodes a novel serine/threonine protein kinase possessing a consensus sequence for an SH3-binding domain from developing rat brain. Rat SBK comprises 417 amino-acid residues consisting of a serine/threonine protein kinase consensus sequence followed by a C-terminal proline-rich region. Sequence comparison with other known kinases revealed that sbk belongs to a novel family of serine/threonine protein kinases structurally related to a Xenopus gastrula-specific protein kinase, Pk9.7. An in vitro kinase assay demonstrated that the SBK protein autophosphorylates at serine/threonine residues. Transcripts of sbk were strongly detected in brain, and the distribution shows an association with neurons but not glial cells. A marked increase in sbk transcripts was observed in developing brain in the late embryonic stage when dramatic neuronal proliferation, migration, and maturation occur. Fluorescence in situ hybridization analysis was used to map sbk to mouse chromosome 7F1-F3 and rat chromosome 1q21. These data suggest a role for SBK in signal-transduction pathways related to the control of brain development.

Amino Acid Sequence↗
PubMed2001

Regulated expression of an actin-associated protein, synaptopodin, during long-term potentiation.

We report NMDA receptor-dependent expression of synaptopodin mRNA in the dentate granule cells of the hippocampus following induction of long-term potentiation (LTP) in vivo. Synaptopodin did not belong to immediate-early genes, as de novo protein synthesis was required for the induction of synaptopodin gene transcription. An increased level of synaptopodin mRNA was observed at 75 min and 3.5 h after the onset of LTP. Importantly, there was correlation between the induction of mRNA expression and the persistence of LTP. Synaptopodin immunoreactivity was elevated specifically in synaptic layers, middle and outer molecular layers of dentate gyrus where LTP was induced. As synaptopodin is an actin-associated protein present in spine neck and implicated in the modulation of cell morphology, our results suggest that synaptopodin, by regulating the dynamics of the actin cytoskeleton, contributes to the morphological change in spine shape considered to be important for the maintenance of synaptic plasticity.

Animals↗
PubMed2000

Detection of an X-Ray Hot Region in the Virgo Cluster of Galaxies with ASCA.

Based on mapping observations with ASCA, an unusual hot region with a spatial extent of 1 deg2 was discovered between M87 and M49 at a center coordinate of R.A.=12h27m36s and decl.=9&j0;18' (J2000). The X-ray emission from the region has a 2-10 keV flux of 1x10-11 ergs s-1 cm-2 and a temperature of kT greater, similar4 keV, which is significantly higher than that in the surrounding medium of approximately 2 keV. The internal thermal energy in the hot region is estimated to be VnkT approximately 1060 ergs with a gas density of approximately 10-4 cm-3. A power-law spectrum with a photon index of 1.7-2.3 is also allowed by the data. The hot region suggests there is an energy input due to a shock that is probably caused by the motion of the gas associated with M49, infalling toward the M87 cluster with a velocity greater, similar1000 km s-1.

Journal Article↗
PubMed2000

A clinical trial to evaluate the effects of flumethrin or ivermectin treatment on hemoparasites, gastrointestinal parasites, conception and daily weight gain in a dairy farm in Japan.

A clinical trial was performed to compare the effects of flumethrin and ivermectin treatments of grazing heifers at one farm in central Japan. 64 heifers were randomly allocated into two groups. Flumethrin (1 mg/kg pour on) was applied approximately once every 3 weeks to heifers in one group and heifers in the second group were injected approximately once every month with ivermectin (200 microg/kg; id). Between groups, no significant differences were detected in the proportions of animals that showed parasitemia of Theileria sergenti and conception risks. Significantly lower average log-transformed nematode-egg counts and higher average daily weight gain were observed in the ivermectin-treated group. Animals with higher body weight at the start of grazing and lower log-transformed total nematode-egg and coccidia-oocyst counts had higher odds of conceiving. Animals with ivermectin treatment, lower body weight at the start of grazing and lower log-transformed coccidia-oocyst count had higher daily weight gain. Ivermectin may be more useful in this farm because of the higher productivity for cattle and lower cost for its usage.

Administration, Cutaneous↗
PubMed1998

Novel members of the Vesl/Homer family of PDZ proteins that bind metabotropic glutamate receptors.

Vesl-1S (186 amino acids, also called Homer) is a protein containing EVH1- and PDZ-like domains whose expression in the hippocampus is regulated during long term potentiation (LTP), one form of synaptic plasticity thought to underlie memory formation (Kato, A., Ozawa, F., Saitoh, Y., Hirai, K., and Inokuchi, K. (1997) FEBS Lett. 412, 183-189; Brakeman, P. R., Lanahan, A. A., O'Brien, R., Roche, K., Barnes, C. A., Huganir, R. L., and Worley, P. F. (1997) Nature 386, 284-288). Here we report additional members of the Vesl/Homer family of proteins, Vesl-1L and Vesl-2. Vesl-1L (366 amino acids), a splicing variant of Vesl-1S, shares N-terminal 175 amino acids with Vesl-1S and contains additional amino acids at the C terminus. Vesl-2 (354 amino acids) was highly related to Vesl-1L in that both contain EVH1- and PDZ-like domains at the N terminus (86% conservation) and an MCC (mutated in colorectal cancer)-like domain and a leucine zipper at the C terminus. In contrast to vesl-1S, we observed no changes in the levels of vesl-1L and vesl-2 mRNAs during dentate gyrus LTP. All these proteins interacted with metabotropic glutamate receptors (mGluR1 and mGluR5) as well as several hippocampal proteins in vitro. Vesl-1L and Vesl-2, but not Vesl-1S, interacted with each other through the C-terminal portion that was absent in Vesl-1S. Vesl-1L and Vesl-2 may mediate clustering of mGluRs at synaptic junctions. We propose that Vesl-1S may be involved in the structural changes that occur at metabotropic glutamatergic synapses during the maintenance phase of LTP by modulating the redistribution of synaptic components.

Amino Acid Sequence↗
PubMed1998

Mode of cell death in the rat metrial gland during peripartum regression.

In the rodent uterus, the metrial gland develops during midpregnancy and undergoes regression prior to parturation. The involution of the gland is reported to be accompanied by the loss of gland cells due to their death in situ. Cell death has been classified by using morphological criteria into two types: necrosis and apoptosis. To study the mechanism involved in the peripartum regression of the rat metrial gland, we examined the mode of cell death in the gland during the last week of gestation. We identified apoptotic cells in the regressing metrial gland by using DNA fragmentation, in situ DNA 3'-end labeling, and electron microscopy. Expression of progesterone receptor (PR) and estrogen receptor (ER) was also demonstrated by immunohistochemistry in the gland. The mean weight of metrial gland nodes decreased after day 18 of pregnancy. The apoptotic granulated metrial gland (GMG) cells that were detected by using the in situ DNA 3'-end labeling method were observed on day 16 of pregnancy, and they increased in number after day 20 of pregnancy. Intense fragmentation of DNA was also found from day 20 to day 22 of pregnancy. Electron microscopy demonstrated apoptotic GMG cells in the regressing metrial glands, confirming the results of the labeling studies. Immunohistochemical study revealed that expression of PR and ER, which were localized mainly in fibroblast-like stromal cells but not in GMG cells, was almost unchanged during late pregnancy. Apoptotic cell death is the major mode of rat metrial gland cell death in the peripartum loss of metrial gland cells.

Animals↗
PubMed1998

[Gamma-heavy chain disease associated with MALT lymphoma of the duodenum].

We report a case of a 63-year-old woman with gamma heavy chain disease (HCD) associated with mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum. She was suffering from drug-resistant tonsillitis with high fever. Examination on admission showed leukocytopenia and thrombocytopenia. Bone marrow aspirate revealed granulocytosis and a hypocellular marrow with no increase in plasma cells or atypical lymphocytes. Serum electrophoresis disclosed, in addition to hypogamma-globulinemia, an abnormal band due to the presence of gamma HCD protein. This abnormal protein was a molecular weight of approximately 40 kd as determined by Western blots technique, and belonged to the IgG1 subclass as determined by ELISA with monoclonal antibodies against IgG. An endoscopic examination of the patient's duodenum found a small tumorous lesion, which was confirmed pathologically to be MALT lymphoma. HCD is known to be associated with lymphoproliferative diseases. In this case, gamma HCD had developed as a secondary complication of MALT lymphoma. gamma HCD associated with MALT lymphoma of the duodenum is rare in the literature.

Biomarkers↗
PubMed1997

Effects of estrogenic hormones on early development of Xenopus laevis.

Many chemicals released into the environment have estrogenic activity and can disrupt animal development and the function of endocrine systems. In order to study the effects of estrogens on aquatic animals, we examined the effects of certain estrogens on early development in Xenopus laevis. X. laevis embryos were kept in water containing 10(-10), 10(-9), 10(-7), 10(-6), and 10(-5) M 17 beta-estradiol (E2); 17 alpha-estradiol; diethylstilbestrol (DES); 10(-5) M progesterone (P); or dihydrotestosterone (DHT) beginning at developmental stage 3. Survival rates of the embryos developed in water containing 10(-10)-10(-6) M E2 or DES, all concentrations of 17 alpha-estradiol, and 10(-5) M P or DHT, which were over 70% after stage 48, whereas the rates of the embryos treated with 10(-5) M E2 and DES decreased remarkably after stage 27 and all embryos were dead by stages 42 and 32, respectively. Embryos treated with 10(-5) M E2 showed malformations of the head and abdomen and suppressed organogenesis, including crooked vertebrae at stage 38; the head was smaller and the abdomen was larger than in the controls. Similar effects were observed in embryos developed in 10(-5) M DES but not in 10(-5) M 17 alpha-estradiol, P, or DHT. After 10(-5) M E2 treatment, abnormalities were induced only when the treatment was started before stage 39. However, on day 30 after fertilization, the stage of the embryos treated with 10(-6) M E2 was more progressed than that of the controls. Estrogen receptor (ER 4) mRNA was examined in eggs, embryos, and adult female liver by reverse-transcription polymerase chain reaction. ER4 mRNA was expressed in adult liver, unfertilized and fertilized eggs, and embryos, but ER3 mRNA was not expressed. ER4 mRNA in 10(-6) and 10(-5) M E2-treated embryos showed different expression patterns, which may result from the diverse developmental effects of E2. The present results demonstrate that 10(-5) M E2 and DES induced embryo death and malformations and that ER may be involved in the induction of various developmental defects in X. laevis embryos.

Abdomen↗
PubMed1997

Apoptotic cell death during the estrous cycle in the rat uterus and vagina.

BACKGROUND: Rodent uterus and vagina show marked histological changes during the estrous cycle. Apoptotic cell death has been demonstrated in hamster and rat uterine epithelium during the estrous cycle by electron microscopy: numerous epithelial cells undergo apoptosis at estrus. We examined cell death and cell proliferation in rat uterus and vagina during estrous cycle. METHODS: To examine the rate of proliferation in uterine and vaginal cells at each estrous stage, the numbers of cells at metaphase were counted separately in epithelial and stromal cells. We identified the apoptotic cells in uterus and vagina at each estrous stage by using DNA fragmentation, in situ DNA 3'-end labeling, and electron microscopy. RESULTS: Mitotic rates in uterine luminal and glandular epithelial cells were low at metestrus and estrus, respectively. Intense fragmentation was found in the uterus at metestrus and in the vagina at proestrus and metestrus. In uterine luminal and glandular epithelial cells, apoptotic index showed peaks at metestrus and estrus, respectively. In vaginal epithelial cells, many apoptotic cells were encountered in the superficial layer at proestrus, which may contribute to keratinization. In the middle and basal layer of vaginal epithelial cells, apoptotic index was high at metestrus, when mitotic rate was low. Electron microscopy confirmed the results of the labeling studies. CONCLUSIONS: Apoptotic cell death was encountered in the uterus and vagina during estrous cycle in rats. There is an inverse correlation between cell death and cell proliferation in rat uterine and vaginal epithelial cells during the estrous cycle.

Animals↗
PubMed1997

Necrotizing funisitis: clinical significance and association with chronic lung disease in premature infants.

OBJECTIVES: Our purpose was to analyze the clinical significance of necrotizing funisitis, an unusual type of chronic inflammation of the umbilical cord, and to determine whether necrotizing funisitis is associated with chronic lung disease in premature infants. STUDY DESIGN: A total of 52 perinatal factors were prospectively assessed in 18 pregnant women and their fetuses in cases of chorioamnionitis at delivery occurring at 22 to 30 gestational weeks; a statistical comparison between the necrotizing funisitis group (n = 5) and the group without necrotizing funisitis (n = 18) was carried out. RESULTS: Significant correlations were found between necrotizing funisitis and the following factors: maternal serum C-reactive protein level on admission (p = 0.014), fetal distress (p = 0.044), umbilical artery blood pH value (p = 0.037) and polynuclear neutrophilic leukocyte count at birth (p = 0.014), chronic lung disease (p = 0.035), need for dexamethasone therapy for chronic lung disease (p = 0.029), duration of oxygen supplementation (p = 0.026), and length of hospital stay (p = 0.026). CONCLUSIONS: There was a significant association between necrotizing funisitis and development of chronic lung disease, suggesting that necrotizing funisitis is an important risk factor for the development of chronic lung disease.

Chorioamnionitis↗
PubMed1997

Anti-chemotactic activity of capsular polysaccharide of Cryptococcus neoformans in vitro.

In this study, we demonstrated the anti-chemotactic activity of the capsular polysaccharides (CPSs) isolated from each of the heavily (H)- and weakly (W)-encapsulated strains of Cryptococcus neoformans in vitro. The capacity for activation of the alternative complement pathway (ACP) of cells of the two C. neoformans strains in fresh human sera was comparable to that of zymosan (insoluble control), whereas the capacity for generation of the chemotactic factor (CF) of the cells of the two strains in fresh murine sera was markedly lower in the order H- < W-strain than that of zymosan. Conversely, the capacities for ACP activation and CF generation of the CPSs were extremely lower than those of lipopolysaccharide (LPS, soluble control). When zymosan-activated murine serum was incubated with CPS, both CPSs inhibited CF activity dose dependently. When zymosan-activated serum was incubated with heat-killed cells of each strain of C. neoformans, H and W, the CF activity of the treated sera decreased significantly, suggesting that CPS per se did not affect the neutrophils directly, but CPS absorbed CF. On the other hand, both CPSs were shown to possess the O-acetyl groups in their molecules by 1H-nuclear magnetic resonance spectroscopy. The de-O-acetylation of both CPSs increased the capacity for ACP activation to a level similar to that of LPS, and the de-O-acetylated CPS of both strains exhibited a lower ability to inhibit CF than did native CPS. Collectively, these results suggest that the anti-chemotactic activity of CPS accounts for its ability to absorb the CF which was mostly generated at the sites around the cell wall of whole cells via the ACP, thus suppressing the inflammatory response by preventing dispersal of CF to the extracellular space; and also that the O-acetyl group is partly, if any, involved in the mechanism for incompetence in ACP activation as well as the inhibition of CF.

Acetylation↗
PubMed1997

Mouse anococcygeus muscle: sexual dimorphism and responsiveness to sex hormones.

The anococcygeus muscle (AcM) is one of a pair of thin sheets of smooth muscle inserting on the rectum, having a tendinous origin largely on sacral vertebrae. The cross-sectional area of AcM in the juxtarectal region in 90-day-old male mice was significantly larger than that in females of three strains: BALB/cCrgl, ICR/Jcl and C57BL/Tw. The AcM area in female mice showed strain differences: BALB/c > ICR > C57BL. Five daily injections of testosterone into newborn ICR mice from the day of birth significantly increased the areas of AcM in both sexes at 30 days of age, but five daily injections of oestradiol-17 beta (OE) decreased them. The AcM area in 60-day-old ICR male mice castrated at 30 days of age was significantly smaller than in intact males, and that in ovariectomized females was significantly larger than in intact females. In both sexes, implantation of a testosterone pellet (12 mg) into gonadectomized mice on the day of gonadectomy stimulated the growth of AcM, and implantation of an OE pellet (12 mg) inhibited the growth of AcM. The AcM in both ICR and C57BL strains showed positive androgen receptor and oestrogen receptor immunostaining at 15 days. Female ICR mice exposed neonatally to diethylstilboestrol (DES) had significantly larger AcM than controls; ovariectomy at 30 days of age did not change the AcM area in 60-day-old DES-exposed mice. However, male mice exposed neonatally to DES had significantly smaller AcM than controls; castration at 30 days of age nullified this inhibition. These results suggest that both androgen and oestrogen play an important role in sexual dimorphism of the mouse AcM. Neonatal exposure to DES (but not to oestradiol) had an irreversible stimulatory effect on the AcM area in female mice.

Animals↗
PubMed1997

[A case report of thymic carcinoid].

A 71-year-old man was admitted to our hospital because of abnormal shadow on the chest X-ray. CT scan showed two tumor masses in the anterior superior mediastinum. The operation was performed through median sternotomy. Two masses, 2.5 x 2.5 x 2.0 cm and 1. x 3.0 x 2.5 cm in size, were found to arise from the right lobe of the thymus. Total thymectomy including resection of the right pleura was performed, and mediastinal lymph nodes were dissected. The pathological diagnosis was thymic carcinoid with metastasis to the anterior mediastinal lymph node. The patient underwent postoperative radiation therapy of total dosage of 50 Gy, and had no evidence of recurrence one year after operation.

Aged↗
PubMed1996

Apoptosis of pregnancy-dependent mammary tumor and transplantable pregnancy-dependent mammary tumor in mice.

Pregnancy-dependent mammary tumors (PDMT) of GR/A mice and transplantable PDMT (TPDMT-4 line) in DDD mice, are exceptionally stable in hormone dependence, continue to grow until parturition and regress soon after delivery. In order to study the regression mechanism of PDMT and TPDMT-4, morphological and biochemical changes were examined in the tumors removed on day 18 (TPDMT-4) or day 20 (PDMT) of pregnancy, and on the expected parturient and the following postpartum days. DNA fragmentation occurred from day 18 (TPDMT-4) or day 20 (PDMT) of pregnancy to the day after parturition. Apoptotic cells were demonstrated by an in situ 3'-end labeling method, and the plateau of the number of apoptotic cells was observed on the parturient day in PDMT and on the day after parturition in TPDMT-4. Reverse transcriptase polymerase chain reaction showed that expression of Fas was slightly increased but that of bcl-2 was decreased during the process of involution of TPDMT-4 and PDMT. These results suggest that both an increase in expression of Fas and decrease in expression of bcl-2 are involved in the apoptosis of pregnancy-dependent mammary tumor cells after parturition.

Animals↗
PubMed1996

Effect of neonatal exposure to diethylstilbestrol and tamoxifen on pelvis and femur in male mice.

BACKGROUND: Permanent abnormalities have been reported in reproductive and non-reproductive organs of mice and humans exposed perinatally to a synthetic estrogen, diethylstilbestrol (DES). Recent studies demonstrated that sex hormones affected the shape of the innominate bone in mice. Therefore, we analyzed the long-term effects of neonatal exposure of DES and tamoxifen, an anti-estrogen, in mouse bones. METHODS: Changes in the pelvis and femur were examined in 1- to 15-month-old C57BL/Tw male mice given 5 daily injections of 3 micrograms DES or of 100 micrograms tamoxifen beginning on the day of birth by measuring contents of calcium (Ca) and phosphorus (P), and the numbers of osteoblasts and osteoclasts. RESULTS: The ash weight of pelvis and femur in neonatally DES- and tamoxifen-treated mice was lower than that in the controls at 2-15 months of age. Contents of Ca and P of pelvis and femur in neonatally tamoxifen-treated mice were lower than in the controls and neonatally DES-treated mice. In neonatally DES-treated mice at 6-12 months, Ca and P contents in the pelvis were lower than in controls, but not different in the femur. The number of osteoblasts per unit length of endocortical surface of the femur in 2- and 3-month-old DES- and tamoxifen-treated mice was lower than that in the controls. The osteoclast number in the femur in DES-treated mice at 2 to 12 months was not different from that in the controls; however, in tamoxifen-treated mice, the number was higher than in the controls. An epiphyseal line was clearly detected in the femur of 12- and 15-month-old DES- and tamoxifen-treated male mice, whereas the line in the controls disappeared after 12 months. CONCLUSIONS: The present results indicate that in male mice, neonatal exposure to DES and tamoxifen induced permanent changes in the pelvis and the femur, and that tamoxifen had a greater effect on bone tissue than did DES.

Age Factors↗