Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 325 records · Page 18Linked to original sources

PubMed1997

Quantitative analysis of GAD65 and GAD67 immunoreactivities in somata of GABAergic neurons in the mouse hippocampus proper (CA1 and CA3 regions), with special reference to parvalbumin-containing neurons.

Intensities of the immunoreactivities against two GAD isoforms, GAD65 and GAD67, were examined quantitatively in somata of GABAergic neurons in the mouse hippocampus proper. All labeled somata contained both isoforms but showed diverse immunoreactivities against them. The somata showing weak immunoreactivity for GAD65 but moderate to intense immunoreactivity for GAD67 were frequently located in the stratum pyramidale of the CA1 and CA3 regions and were mainly composed of parvalbumin-containing neurons, a particular subpopulation of hippocampal GABAergic neurons. These data revealed additional distinctive properties of parvalbumin-containing neurons and suggest their specialized roles in the hippocampal GABAergic system.

Animals↗

PubMed1997

Effects of ketamine on dopamine metabolism during anesthesia in discrete brain regions in mice: comparison with the effects during the recovery and subanesthetic phases.

The effects of ketamine on the levels of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT, serotonin) and their metabolites were examined in discrete brain regions in mice. A high dose of ketamine (150 mg/kg, i.p.) did not change DA metabolism in the frontal cortex, nucleus accumbens, striatum and hippocampus, but did decrease it in the brainstem during anesthesia. In contrast, during recovery from the ketamine anesthesia, the high dose increased the level of homovanillic acid (HVA) in all brain regions. A low subanesthetic dose of ketamine (30 mg/kg, i.p.) increased the concentrations of both 3,4-dihydroxyphenylacetic acid (DOPAC) and HVA only in the nucleus accumbens. The DA level was not affected by any ketamine treatment. During ketamine anesthesia, the content of 3-methoxy-4-hydroxy-phenylglycol (MHPG) was decreased in the brainstem, whereas during recovery from anesthesia, the MHPG level was increased in the frontal cortex, nucleus accumbens and brainstem. The NE content was not altered in any region by ketamine treatment. The concentration of 5-hydroxyindoleacetic acid (5-HIAA) was reduced in the frontal cortex, striatum, hippocampus and brainstem during ketamine anesthesia. The 5-HT level was unaltered in all regions except the brainstem where it was reduced. In contrast, after anesthesia, the concentrations of both 5-HT and 5-HIAA were increased in the striatum. During the subanesthetic phase, however, the levels of NE, 5-HT and their metabolites were unchanged. These neurochemical results are consistent with the electrophysiological findings that a high dose of ketamine does not change the basal firing rates of nigrostriatal DA neurons during anesthesia, while low subanesthetic doses significantly increase those of ventral tegmental DA neurons.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Expression and intracellular localization of heat shock proteins in multidrug resistance of a cisplatin resistant human ovarian cancer cell line.

TYK-R10 is a cisplatin resistant human ovarian carcinoma cell line and showed a cross resistance to various anti-cancer drugs including adriamycin (ADR), vincristine (VCR) and etoposide, despite a lack of multidrug phenotype. Under normal conditions, various heat shock proteins (HSPs) were expressed in TYK-R10 but not in parental line (TYK-nu). Non-lethal short-term heat shock treatment induced a high tolerance for cisplatin and VCR in TYK-R10 and ADR, and VCR in TYK-nu. This treatment induced and/or enhanced the expression of various types of HSPs in various intracellular localizations in both TYK-R10 and TYK-nu, with minor differences. These findings indicate that combined expression and intracellular localization of HSPs may play an important role in drug resistance of TYK-R10.

Cisplatin↗

PubMed1997

Immunohistochemical localization of neurocan and L1 in the formation of thalamocortical pathway of developing rats.

We used immunohistochemistry to examine possible molecular interactions between the subplate and growing thalamocortical axons in rat fetuses. In the cortical anlage of embryonic day 16 (E16), the subplate first appeared below the cortical plate. Among chondroitin sulfate proteoglycans, phosphacan was uniformly distributed throughout the cortical wall, whereas neurocan was localized only in the subplate at E16. Neural cell adhesion molecules, NCAM-H, TAG-1, and L1, were detected in the cortical anlage. Both cortical neurons and growing axons were diffusely immunopositive for NCAM-H, and TAG-1 immunoreactivity was found on immature neurons and cortical efferent axons but not on thalamocortical axons. L1 immunoreactivity was specifically localized on the growing thalamocortical axons. When the locations of neurocan and L1 were compared in the developing cortex, L1-bearing axons were found to extend to neurocan-immunopositive regions; neurocan immunoreactivity was intense in the subplate at E16, when small numbers of L1-immunoreactive thalamocortical axons began to invade the cortex. At E17, many L1-positive axons were observed in the subplate that expressed neurocan specifically. Double immunostaining showed that L1-positive axons and neurocan immunoreactivity overlapped in the subplate at E17. After E18, neurocan expression gradually extended to the lower part of the cortical plate; it extended to the entire cortex by E21, 1 day before birth. By E21, L1-bearing axons had invaded the lower part of the cortical plate. The present study demonstrated that the neurocan expression precedes growth of L1-bearing thalamocortical afferent fibers. Because neurocan can bind to L1 molecule in vitro, these results suggest that neurocan and L1 play some important roles in pathfinding of the thalamocortical afferent fibers during rat corticogenesis.

Animals↗

PubMed1997

Role of tyrosine phosphorylation of HS1 in B cell antigen receptor-mediated apoptosis.

The 75-kD HS1 protein is highly tyrosine-phosphorylated during B cell antigen receptor (BCR)-mediated signaling. Owing to low expression of HS1, WEHI-231-derived M1 cells, unlike the parental cells, are insensitive to BCR-mediated apoptosis. Here, we show that BCR-associated tyrosine kinases Lyn and Syk synergistically phosphorylate HS1, and that Tyr-378 and Tyr-397 of HS1 are the critical residues for its BCR-induced phosphorylation. In addition, unlike wild-type HS1, a mutant HS1 carrying the mutations Phe-378 and Phe-397 was unable to render M1 cells sensitive to apoptosis. Wild-type HS1, but not the mutant, localized to the nucleus under the synergy of Lyn and Syk. Thus, tyrosine phosphorylation of HS1 is required for BCR-induced apoptosis and nuclear translocation of HS1 may be a prerequisite for B cell apoptosis.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Distribution of nonprincipal neurons in the rat hippocampus, with special reference to their dorsoventral difference.

In the present study we examined the distribution of chemically identified subpopulations of nonprincipal neurons in the rat hippocampus, focusing on the dorsoventral differences in their distributions. The subpopulations analyzed were those immunoreactive for parvalbumin, calretinin, nitric oxide synthase, somatostatin, calbindin D28K, vasoactive intestinal polypeptide and cholecystokinin. Using a confocal laser scanning light microscope, we could confirm that the penetration of each immunostaining, except that of calbindin D28K, was complete throughout 50 microns thick sections under our immunostaining conditions. We counted numbers of immunoreactive somata according to the 'dissector' principle, measured areas of hippocampal subdivisions and the thickness of sections, and estimated the approximate numerical densities of these subpopulations, especially for those neurons immunoreactive for nitric oxide synthase, calretinin, somatostatin and parvalbumin. Generally speaking, neurons immunoreactive for parvalbumin showed no significant dorsoventral differences in the numerical densities in any of the subdivisions of the hippocampus, whereas the numerical densities of somata immunoreactive for calretinin, nitric oxide synthase and somatostatin were significantly larger in ventral levels than at dorsal levels of the hippocampus. The numerical density of somatostatin neurons was significantly larger in ventral levels than in dorsal levels of the denate gyrus, and, although not prominent, of the CA1 region. That of nitric oxide synthase positive neurons was significantly larger in ventral levels than in dorsal levels of the CA3 region as well as of the DG but not of the CA1 region. The numerical density of calretinin positive neurons was larger in ventral levels than in dorsal levels of all hippocampal subdivisions. The present study also revealed that dorsal and ventral levels of the hippocampus differ from each other in the composition of their nonprincipal neurons.

Animals↗

PubMed1997

Hydrogen peroxide-mediated degradation of protein: different oxidation modes of copper- and iron-dependent hydroxyl radicals on the degradation of albumin.

Cupric ions (Cu2+) added to hydrogen peroxide (H2O2) were found to generate hydroxyl radicals (HO) capable of benzoate hydroxylation. Although ferrous (Fe2+) and ferric (Fe3+) ions, when added to H2O2, resulted in very little production of HO, the addition of EDTA to the reaction mixture markedly increased their catalytic activity. In the absence of albumin, catalase (a H2O2 scavenger) and mannitol (an HO radical scavenger) effectively inhibited the formation of HO in H2O2/Cu2+ and H2O2/Fe2+/EDTA oxidation systems. On analysis using SDS-polyacrylamide gel electrophoresis, catalase was shown to prevent the degradation of albumin by both oxidation systems, whereas mannitol was an effective scavenger of the H2O2/Fe2+/EDTA oxidation system but not of the H2O2/Cu2+ oxidation system. Furthermore, the effect of alteration of benzoate hydroxylation and H2O2 consumption on the H2O2/Cu2+ and H2O2/Fe2+/EDTA oxidation systems resulted in opposite behavior that was dependent upon the presence or absence of albumin. These observations suggest that copper ions bind to albumin and induce site-specific degradation by HO generated at the copper-binding site, whereas the Fe2+/EDTA-catalyzed oxidation system induces non-specific degradation of albumin by HO generated by the Fenton reaction between H2O2 and free Fe2+/EDTA in solution.

Albumins↗

PubMed1997

Shortened telomere length and increased telomerase activity in hamster pancreatic duct adenocarcinomas and cell lines.

Recently, shortened telomere length and increased telomerase activity have been demonstrated in various human cancers. In the study reported here, we ascertained whether gene changes are characteristic of pancreatic cancers. Hamster duct carcinomas and cell lines were investigated by Southern blot analysis for telomere restriction fragment (TRF) length and by the telomeric repeat amplification protocol (TRAP) assay for telomerase activity. Comparison with normal pancreas and spleen revealed shortened TRF length and markedly increased telomerase activity in primary pancreatic duct carcinomas induced by the rapid-production model as well as in a transplantable carcinoma and the cell lines. The enzyme level was 86.0-215.7 times the low levels found in control pancreas and spleen tissues. Late-passage Syrian hamster embryo cells, known to be immortalized and tumorigenic, had shorter TRFs than the original cells in primary culture did. These results indicate that hamster pancreatic duct carcinoma cells are immortalized, with the potential for proliferation ad infinitum, and provide a model for basic therapeutic research into the substances targeting telomerase.

Adenocarcinoma↗

PubMed1997

Ascending aorta to supraceliac abdominal aorta bypass for coarctation of the aorta in an adult.

We present herein a case of ascending aorta to supraceliac abdominal aorta bypass for coarctation of the aorta in a 46-year-old woman with a history of hypertension. Because of severe calcification of the coarctation segment, we performed an ascending aorta to supraceliac abdominal aorta bypass instead of a conventional resection and anastomosis of the coarctation segment. Following surgery, the patient's blood pressure normalized, and she was discharged on the 14th postoperative day without any complications. An ascending aorta to supraceliac abdominal aorta bypass for coarctation of the aorta in adults is thus considered to be safe and easy to perform.

Aorta↗

PubMed1997

Primary cardiac angiosarcoma: 53 months' survival after multidisciplinary therapy.

An 8-year-old girl underwent surgical excision of a tumor arising from the right atrium immediately after admission. Because histologic and immunohistochemical examination confirmed the diagnosis of angiosarcoma, adjunctive multidisciplinary therapy was administered for the following 2 years. She is leading a normal school life 53 months after the operation. Therapeutic strategy for this highly malignant cardiac tumor is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Nitric oxide stimulates prostaglandin synthesis in cultured rabbit gastric cells.

Both prostaglandins (PGs) and nitric oxide (NO) have cytoprotective and hyperemic effects in the stomach. However, the effect of NO on PG synthesis in gastric mucosal cells is unclear. We examined whether sodium nitroprusside (SNP), a releaser of NO, stimulates PG synthesis in cultured rabbit gastric mucus-producing cells. These cells did not release NO themselves. Co-incubation with SNP (2 x 10(-4), 5 x 10(-4), 10(-3) M) increased PGE2 synthesis, and SNP (10(-3) M) increased PGI2 synthesis in these cells. Hemoglobin, a scavenger of NO, (10(-5) M) eliminated the increase in PGE2 synthesis by SNP, but methylene blue, an inhibitor of soluble guanylate cyclase, (5 x 10(-5) M) did not affect the increase in PGE2 synthesis by SNP. 8-bromo guanosine 3':5'-cyclic monophosphate (8-bromo cGMP), a cGMP analogue, (10(-6), 10(-5), 10(-4), 10(-3) M) did not affect PGE2 synthesis. These findings suggest that NO increased PGE2 and PGI2 synthesis via a cGMP-independent pathway in cultured rabbit gastric cells.

Animals↗

PubMed1997

Cu, Zn-superoxide dismutase reaction in neonatal pontosubicular neuron necrosis.

The immunohistochemical localization and changes in copper/zinc superoxide dismutase (Cu, Zn-SOD) were examined in 14 neonates with pontosubicular neuron necrosis (PSN), as compared with those in 15 controls in which the cytoplasm of neurons and glial cells showed SOD immunoreactivity. In the temporal lobes and hippocampus with PSN, Cu, Zn-SOD reactivity was negative in neurons at 0 and 1 days after birth, but was positive after 5 days of age in 8 of 10 cases. In the pons and cerebellum, SOD-positive neurons appeared soon after birth, but eosinophilic or karyorrhectic neurons were SOD negative. On the other hand, glial cells were positive after birth in all cases of PSN, and their reactivity was increased in the cases of reactive astrogliosis. Early loss of the scavenging system directed at free radicals may lead to neuronal damage, and the induction of Cu, Zn-SOD may act as a defense mechanism against damage of neurons in neonates with PSN. Therefore, oxygen-derived free radicals may be one of the pathogenetic factors of PSN with characteristics of apoptosis in neonates.

Case-Control Studies↗

PubMed1997

Retrograde cerebral perfusion through antero-axillary thoracotomy in the aortic arch surgery.

OBJECTIVE: We have recently found that left antero-axillary thoracotomy provides an ideal view of aortic arch and makes the direct cannulation to superior vena cava possible for retrograde cerebral perfusion during circulatory arrest. METHOD: Twelve patients with distal aortic arch aneurysm or aortic dissection underwent the repair of aortic arch through this approach. Mean duration of retrograde cerebral perfusion was 41 min. RESULTS: Two hospital deaths occurred due to respiratory failure and stroke. The remaining patients survived without any neurological deficits. CONCLUSION: Antero-axillary thoracotomy may be an ideal approach which combines the advantages of median sternotomy and postero-lateral thoracotomy.

Adult↗

PubMed1997

Multistage regulation of Th1-type immune responses by the transcription factor IRF-1.

Eradication of a given pathogen is dependent on the selective differentiation of T helper (Th) cells into Th1 or Th2 types. We show here that T cells from mice lacking the transcription factor IRF-1 fail to mount Th1 responses and instead exclusively undergo Th2 differentiation in vitro. Compromised Th1 differentiation is found to be associated with defects in multiple cell types, namely impaired production of interleukin-12 by macrophages, hyporesponsiveness of CD4+ T cells to interleukin-12, and defective development of natural killer cells. These results indicate the involvement of IRF-1 in multiple stages of the Th1 limb of the immune response.

Animals↗

PubMed1997

Interleukin-8 stimulates leukocyte migration across a monolayer of cultured rabbit gastric epithelial cells. Effect associated with the impairment of gastric epithelial barrier function.

Acute Helicobacter pylori infection produces predominantly neutrophilic infiltration of the gastric mucosa. However, the precise mechanisms and mediators of neutrophil migration are not known. Interleukin-8 (IL-8), a potent chemotactic factor for neutrophils, is present at high concentration in the gastric mucosa of subjects with chronic gastritis caused by H. pylori infection. The aims of this study were to determine whether IL-8 stimulates polymorphonuclear leukocyte (PMN) migration across a cultured monolayer of rabbit gastric epithelial cells and whether PMN migration affects epithelial cell barrier function. Confluent gastric epithelial monolayers grown on the inserts were overlaid with PMNs and various amounts of IL-8 were administered into the well under the insert. Gastric epithelial barrier function was assessed by sodium back diffusion. IL-8 stimulated PMN migration across the monolayer in a dose- and time-dependent manner. PMN transmigration significantly increased sodium back diffusion. In conclusion, IL-8 induces PMN migration across a monolayer of cultured gastric epithelial cells. This IL-8 action is associated with impairment of gastric epithelial barrier function. Since H. pylori infection causes a local mucosal increase of IL-8, our present findings may explain the mechanism of H. pylori-induced PMN infiltration of the gastric glands and mucosal injury.

Animals↗

PubMed1997

The effects of a simplified method for cryopreservation and thawing procedures on peripheral blood stem cells.

A simplified method for cryopreservation at -80 degrees C of peripheral blood stem cells (PBSC) has been increasingly used for autologous PBSC transplantation in Japan. Although this method, using 6% hydroxyethyl starch (HES) and 5% dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing, has several advantages over the conventional method using 10% DMSO with rate-controlled freezing, little is known about effects of long-term cryopreservation for years and thawing process on hematopoietic progenitors. We examined the recovery rates of BFU-E and CFU-GM in sample tubes cryopreserved by the simplified method under various conditions as follows: (1) long-term storage for 1-5 years; (2) DMSO exposure for 1 h after rapid thawing; and (3) thawing at a lower temperature other than 37 degrees C. In our study, we found that the recovery rates of BFU-E and CFU-GM were not affected by the length of cryopreservation period; they remained at more than 70% on average for 16-61 months. In our hands, a 1-h exposure to DMSO after rapid thawing was not toxic for hematopoietic progenitors. Furthermore, there was no significant difference in the recovery rates of BFU-E and CFU-GM between thawing at 37 degrees C and 20 degrees C. These observations indicate that PBSC cryopreserved for at least 5 years by the simplified method can be used clinically without losing hematopoietic activity, and suggest that hematopoietic activity of the thawed PBSC may be unaffected when PBSC are infused slowly within 60 min or even when PBSC are thawed gradually at room temperature.

Blood Preservation↗

PubMed1997

Pigmented renal cell carcinoma: accumulation of abnormal lysosomal granules.

AIMS: Five cases of renal cell carcinoma (RCC) with abnormal pigmentation have been examined by histochemical, immunohistochemical and ultrastructural methods. METHODS AND RESULTS: Compared with conventional RCCs, there was no difference in histological findings of each case, except for the presence of pigmented cells. In three cases, tumour cells possessing various sized brown granules with neuromelanin-like features were scattered throughout the tumour. The granules observed in one of the others were angulated lysosomes and in another tumour cells in the pigmented areas possessed the granules closely resembling those of granular cell tumour. However, melanosome or neurosecretory granules could not be detected in any of the cases examined. In three cases, some of these abnormal granules showed a weak acid phosphatase activity. On immunohistochemical examination, tumour cells showed a positive immunoreaction for epithelial markers and lacked any antigens suggesting neuroectodermal or neuroendocrine differentiation. The granules in three cases were faintly positive for lysozyme and KP-1. CONCLUSIONS: These findings indicate that abnormal pigmentation of RCCs examined in this study is attributed to accumulation of abnormal lysosomal granules in the neoplastic cells.

Adult↗

PubMed1997

Parasites of the Asian tiger mosquito and other container-inhabiting mosquitoes (Diptera:Culicidae) in northcentral Florida.

Seven microorganisms including 4 protozoans, 2 fungi, and a bacterium infected Aedes albopictus (Skuse) larvae collected from 12 counties in northecentral Florida. Ae albopictus and 14 other species of mosquitoes were collected from tires, flower-holding vases in cemeteries, other types of artificial containers, and treeholes. Ascogregarina taiwanensis (Lien & Levine) was the most common parasite of Ae. albopictus throughout the year. The microsporidium Vavraia culicis (Weiser) infected Aedes aegypti (L.), Ae. albopictus, Aedes triseriatus (Say), and Orthopodomyia sinifera (Coquillett). A vibrio bacterium and 2 fungi (Leptolegnia sp. and Smittium culisetae Lichtwardt), infected Ae. albopictus larvae but were observed infrequently. A. taiwanensis, S. culisetae, and the vibrio bacterium previously have been reported from Ae. albopictus. This is the 1st report of the other 4 microorganisms parasitizing Ae. albopictus larvae.

Aedes↗