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N Sakai

Publications and source records attributed to N Sakai.

At least 271 records · Page 15Linked to original sources
PubMed1998

[Eosinophilic cystitis induced by tranilast: a case report].

We report a patient with tranilast-induced eosinophilic cystitis who had no allergies, but had been administered tranilast to reduce prednisolone. A 62-year-old man presented with macroscopic hematuria and bladder irritative symptoms. The patient had a past medical history of idiopathic thrombocytopenic purpula and had been treated with 15 mg of prednisolone since 1980. He had been receiving 300 mg of tranilast for the past 18 months. Urinalysis revealed a marked increase in eosinophils (4 x 10(4)/ml). A cystoscopic examination revealed reddish mucosa throughout the bladder. A retrograde cystogram showed incomplete bilateral vesicoureteral reflux. Histological examinations of biopsied bladder specimens revealed a marked increase in the number of eosinophils (1,126/mm2), but not of mast cells (12/mm2). The symptoms resolved within one week after cessation of tranilast.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Leiomyoma of the spermatic cord extending along the vas deferens.

We report an unusual case of a leiomyoma of the spermatic cord. The tumor did not present as a mass but presented as a hard structure along the spermatic cord. To our knowledge, this is the first case report of a leiomyoma of the spermatic cord with such an unusual appearance.

Aged↗
PubMed1998

[Factitious anemia with severe iron deficiency caused by self-venesection].

A 22-year-old unmarried female student of nurse school was admitted to our hospital because of hypochromic anemia and fever of unknown origin. She was diagnosed as having iron-deficiency anemia and was treated with iron, but progressive anemia recurred periodically. In particular, rapidly progressive anemia was observed after the patient stayed overnight, so we strongly suspected factitious anemia. A search of her locker in the sickroom and her room at home revealed many syringes, injection needles and a bottle of blood. Factitious anemia was diagnosed and she confessed to self blood-drawing. After a psychiatric consultation, anemia tended to to resolve gradually. However she did not go to the hospital after 6 months from her discharge. Physicians should consider factitious anemia in a patient with severe chronic hypochromic anemia who dose not respond to adequate iron therapy, particularly in a patient with medical training.

Adult↗
PubMed1998

[Retroperitoneal Castleman's disease: a case report].

We report a case of retroperitoneal Castleman's disease. A 57-year-old woman was referred for evaluation of microscopic hematuria. Computed tomography demonstrated a small solid retroperitoneal mass. The mass was surgically resected and the histopathological diagnosis of the resected tissue was hyalin vascular type of Castleman's disease. Although retroperitoneal Castleman's disease is an uncommon disease. We should always consider this tumor in the differential diagnosis of retroperitoneal tumors.

Castleman Disease↗
PubMed1997

BDNF potentiates spontaneous Ca2+ oscillations in cultured hippocampal neurons.

Brain-derived neurotrophic factor (BDNF) is thought to regulate neuronal plasticity in developing and matured neurons, although the molecular mechanisms are less well characterized. We monitored changes in the intracellular calcium (Ca2+) levels induced by BDNF using a fluorescence Ca2+ indicator (Fluo-3) by means of confocal laser microscopy in rat cultured hippocampal neurons. BDNF acutely potentiated spontaneous Ca2+ oscillations in dendrites and also in the soma of several neurons, although it increased intracellular Ca2+ in only selective proportion of resting neurons without Ca2+ oscillations. The potentiation was observed both in the frequency and the amplitude of Ca2+ oscillations, completely blocked by K-252a, and significantly reduced by 2-aminophosphonovaleric acid. These findings suggest that BDNF increases glutamate release and N-methyl-D-aspartate (NMDA) channel-gated Ca2+ influx via TrkB and regulates the frequency and the amplitude of Ca2+ oscillations. BDNF may have the potential to modulate spontaneous Ca2+ oscillations to regulate neuronal plasticity in developing hippocampal neurons.

2-Amino-5-phosphonovalerate↗
PubMed1997

Direct visualization of the translocation of the gamma-subspecies of protein kinase C in living cells using fusion proteins with green fluorescent protein.

We expressed the gamma-subspecies of protein kinase C (gamma-PKC) fused with green fluorescent protein (GFP) in various cell lines and observed the movement of this fusion protein in living cells under a confocal laser scanning fluorescent microscope. gamma-PKC-GFP fusion protein had enzymological properties very similar to that of native gamma-PKC. The fluorescence of gamma-PKC- GFP was observed throughout the cytoplasm in transiently transfected COS-7 cells. Stimulation by an active phorbol ester (12-O-tetradecanoylphorbol 13-acetate [TPA]) but not by an inactive phorbol ester (4alpha-phorbol 12, 13-didecanoate) induced a significant translocation of gamma-PKC-GFP from cytoplasm to the plasma membrane. A23187, a Ca2+ ionophore, induced a more rapid translocation of gamma-PKC-GFP than TPA. The A23187-induced translocation was abolished by elimination of extracellular and intracellular Ca2+. TPA- induced translocation of gamma-PKC-GFP was unidirected, while Ca2+ ionophore-induced translocation was reversible; that is, gamma-PKC-GFP translocated to the membrane returned to the cytosol and finally accumulated as patchy dots on the plasma membrane. To investigate the significance of C1 and C2 domains of gamma-PKC in translocation, we expressed mutant gamma-PKC-GFP fusion protein in which the two cysteine rich regions in the C1 region were disrupted (designated as BS 238) or the C2 region was deleted (BS 239). BS 238 mutant was translocated by Ca2+ ionophore but not by TPA. In contrast, BS 239 mutant was translocated by TPA but not by Ca2+ ionophore. To examine the translocation of gamma-PKC-GFP under physiological conditions, we expressed it in NG-108 cells, N-methyl-D-aspartate (NMDA) receptor-transfected COS-7 cells, or CHO cells expressing metabotropic glutamate receptor 1 (CHO/mGluR1 cells). In NG-108 cells , K+ depolarization induced rapid translocation of gamma-PKC-GFP. In NMDA receptor-transfected COS-7 cells, application of NMDA plus glycine also translocated gamma-PKC-GFP. Furthermore, rapid translocation and sequential retranslocation of gamma-PKC-GFP were observed in CHO/ mGluR1 cells on stimulation with the receptor. Neither cytochalasin D nor colchicine affected the translocation of gamma-PKC-GFP, indicating that translocation of gamma-PKC was independent of actin and microtubule. gamma-PKC-GFP fusion protein is a useful tool for investigating the molecular mechanism of gamma-PKC translocation and the role of gamma-PKC in the central nervous system.

3T3 Cells↗
PubMed1997

GABAergic neurotransmission in rat taste buds: immunocytochemical study for GABA and GABA transporter subtypes.

Gamma-aminobutyric acid (GABA) is known to be a candidate for the neurotransmitter involved in the sense of taste. We hereby studied GABA and its termination system, GABA transporters, in rat taste buds by immunocytochemical approaches. Immunoblot analysis of three GABA transporter subtypes (GAT1, GAT2 and GAT3) revealed that the immunoreactive bands of GAT2 and GAT3, but not GAT1, were detected in the tongue. GAT3-immunoreactive band was recognized only in the circumvallate papilla containing a large number of taste buds while GAT2-immunoreactive bands were seen in all areas of the tongue. GAT2 immunoreactivity appeared to be specifically in the nerve fibers beneath the lingual epithelium. Both GAT3 and GABA immunoreactivities were detected only in taste buds. A few GAT3-immunoreactive cells were found in a cross-section of each taste bud but most GAT3-immunoreactive cells were localized in the margin of the taste bud. GAT3 was predominantly concentrated in the distal portion of the GAT3-immunoreactive cells. In contrast, GABA-immunoreactive cells were seen more frequently within each taste bud and the immunoreactivity was distributed throughout the perikarya of the cells. These results suggest that the GABA-uptake system is present in the taste buds and the GABAergic neurotransmission involved in the sensation of taste is terminated by the uptake of GABA into certain taste cells via GAT3.

Animals↗
PubMed1997

Ornithine decarboxylase inhibitor lessens the rat gastric carcinogenesis enhancement caused by tyrosine methyl ester.

The effects of combined administration of a catecholamine precursor, tyrosine methyl ester (TME), and an ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the incidence of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the norepinephrine (NE) concentration and ODC activity of the gastric wall, and the labeling index of the gastric mucosa were investigated in inbred Wistar rats. Rats received s.c. injections of TME, 512 mg/kg body weight, every other day and drinking water with or without 2.5 g/l of DAP after 25 weeks of oral administration of MNNG. At week 52, administration of TME resulted in significant increases in the incidence of gastric cancers, in the NE concentration and the ODC activity of the antral portion of the gastric wall, and in the labeling index of antral epithelial cells. Administration of both TME and DAP significantly reduced the enhancements by TME of gastric carcinogenesis, NE concentration and ODC activity of the antral wall, and the labeling index of the antral mucosa. Our results suggest that ODC inhibition lessens enhancement by TME of gastric carcinogenesis and that the enhancement by TME of gastric carcinogenesis is mediated in part by polyamine biosynthesis.

Animals↗
PubMed1997

The significant role of telomerase activity in human brain tumors.

BACKGROUND: In this study, telomerase activity in human brain tumors was analyzed. METHODS: Telomerase activity was examined in 41 brain tumor cases (20 of glioblastoma multiformes [GBMs] [14 primary tumors and 6 recurrent tumors], 3 anaplastic astrocytomas [AAs], 4 low grade astrocytomas [LGAs] [World Health Organization Grade 2], 2 oligodendrogliomas [OGs], 9 meningiomas [MNs], and 3 metastatic brain tumors [MBTs]) by means of telomeric repeat amplification protocol assay. The activity of telomerase was compared with histologic diagnosis, the MIB-1 proliferative cell index (PCI), and the patient's prognosis. RESULTS: Twelve of 20 GBMs, 2 of 2 OGs, and 3 of 3 MBTs demonstrated telomerase activity. AAs, LGAs, and MNs exhibited no activity. No clear correlations were confirmed in GBMs between telomerase activity and the MIB-1 PCI data. However, the telomerase activity tended to correlate with the patient's prognosis. CONCLUSIONS: These results suggest that telomerase activity may be an important marker of brain tumor malignancy. Furthermore, the change from negative activity to positive activity in the recurrent tumors appeared to be a useful prognosticator for malignant astrocytic tumor.

Antigens, Nuclear↗
PubMed1997

Inhibition of apoptosis by the actin-regulatory protein gelsolin.

Gelsolin is an actin-regulatory protein that modulates actin assembly and disassembly, and is believed to regulate cell motility in vivo through modulation of the actin network. In addition to its actin-regulatory function, gelsolin has also been proposed to affect cell growth. Our present experiments have tested the possible involvement of gelsolin in the regulation of apoptosis, which is significantly affected by growth. When overexpressed in Jurkat cells, gelsolin strongly inhibited apoptosis induced by anti-Fas antibody, C2-ceramide or dexamethasone, without changing the F-actin morphology or the levels of Fas or Bcl-2 family proteins. Upon the induction of apoptosis, an increase in CPP32(-like) protease activity was observed in the control vector transfectants, while it was strongly suppressed in the gelsolin transfectants. Pro-CPP32 protein, an inactive form of CPP32 protease, remained uncleaved by anti-Fas treatment in the gelsolin transfectants, indicating that gelsolin blocks upstream of this protease. The tetrapeptide inhibitor of CPP32(-like) proteases strongly inhibited Fas-mediated apoptosis, but only partially suppressed both C2-ceramide- and dexamethasone-induced apoptosis. These data suggest that the critical target responsible for the execution of apoptosis may exist upstream of CPP32(-like) proteases in Jurkat cells and that gelsolin acts on this target to inhibit the apoptotic cell death program.

Actins↗
PubMed1997

Conditioned taste aversion and c-fos expression in the rat brainstem after administration of various USs.

Conditioned taste aversion (CTA) is a form of association learning established when an animal associates a conditioned stimulus (taste) with a subsequent unconditioned stimulus (US, illness). We have studied the relationship between the efficacy of inducing CTA to 0.1% saccharin and c-fos expression in the lower brain stem following administration of 13 different USs in rats. The effective USs were grouped into abdominal irritants, rewarding drugs and emetic agents. Regardless of the properties of USs, good correlation was detected between the strength of CTA and c-fos expression within the area postrema, caudal and intermediate subdivisions of nucleus tractus solitarius and the external lateral subnucleus of the parabrachial nucleus. Only hypertonic saline was exceptional because of the experimental procedure: it induced strong c-fos expression, but was not an effective US for CTA formation. Different dosages of the emetic LiCl induced CTA and c-fos expression in a dose-dependent manner.

Animals↗
PubMed1997

Identification of differentially expressed mRNAs during rat C6 glial cell differentiation by mRNA fingerprinting using arbitrarily primed PCR (RAP).

Differentiation of glial cells is controlled by a complex program of differential expressions of many genes. To identify differentially expressed genes that are involved in rat C6 glial cell differentiation induced by dibutyryl cyclic AMP and theophylline, mRNA fingerprinting using arbitrarily primed PCR (RAP) was used. Four cDNA fragments, that were differentially expressed during differentiation, were isolated. Sequence analysis revealed that one of them, abundantly expressed during differentiation, was homologous to a hamster calcium-dependent serine protease. Another one was highly similar to rabbit dystrobrevin and the other two clones were identical to rat triose phosphate isomerase and calnexin. The results obtained suggest that the expressions of particular genes were changed and that RAP is a useful method to identify genes which are differentially expressed during glial cell differentiation.

Animals↗
PubMed1997

Disulfide bond formation is not involved in cap-binding activity of Xenopus translation initiation factor eIF-4E.

The eukaryotic initiation factor eIF-4E from Xenopus laevis was expressed in Escherichia coli and refolded in an active form. To define the cysteine residues forming a disulfide bond in Xenopus eIF-4E, each of the 3 cysteine residues was changed to serine by site-directed mutagenesis. Cap-binding activities of the mutant proteins were evaluated by 7-methyl-GTP(m7GTP)-affinity column chromatography. Even the mutant protein containing no cysteine showed an affinity for m7GTP. From the above results and the estimation of the sulfhydryl groups by Ellman's assay method, we concluded that a disulfide bond is not involved in the active Xenopus eIF-4E.

Amino Acid Sequence↗
PubMed1997

Gustatory and visceral inputs to the amygdala of the rat: conditioned taste aversion and induction of c-fos-like immunoreactivity.

Expression of proto-oncogene c-fos was immunohistochemically examined in the central and basolateral amygdaloid nuclei in rats after ingestion of taste solutions (0.5 M sucrose or 0.005 M saccharin), intragastric infusion of these solutions, or an intraperitoneal injection of malaise-inducing lithium chloride (LiCl). C-Fos-like immunoreactive neurons were distributed most densely in the central nucleus in response to the LiCl injection, followed by the ingestion and intragastric infusion of sucrose. The intraoral infusion of sucrose, but not of saccharin, elicited intense c-fos expression in the central nucleus after establishment of conditioned taste aversion to these taste stimuli. The results are discussed in terms of post-ingestional factors and the conditioned illness reaction after taste aversion learning.

Administration, Oral↗
PubMed1997

Targeted disruption of the mouse lecithin:cholesterol acyltransferase (LCAT) gene. Generation of a new animal model for human LCAT deficiency.

We have established a mouse model for human LCAT deficiency by performing targeted disruption of the LCAT gene in mouse embryonic stem cells. Homozygous LCAT-deficient mice were healthy at birth and fertile. Compared with age-matched wild-type littermates, the LCAT activity in heterozygous and homozygous knockout mice was reduced by 30 and 99%, respectively. LCAT deficiency resulted in significant reductions in the plasma concentrations of total cholesterol, HDL cholesterol, and apoA-I in both LCAT -/- mice (25, 7, and 12%; p < 0. 001 of normal) and LCAT +/- mice (65 and 59%; p < 0.001 and 81%; not significant, p = 0.17 of normal). In addition, plasma triglycerides were significantly higher (212% of normal; p < 0.01) in male homozygous knockout mice compared with wild-type animals but remained normal in female knockout LCAT mice. Analyses of plasma lipoproteins by fast protein liquid chromatography and two-dimensional gel electrophoresis demonstrated the presence of heterogenous prebeta-migrating HDL, as well as triglyceride-enriched very low density lipoprotein. After 3 weeks on a high-fat high-cholesterol diet, LCAT -/- mice had significantly lower plasma concentrations of total cholesterol, reflecting reduced levels of both proatherogenic apoB-containing lipoproteins as well as HDL, compared with controls. Thus, we demonstrate for the first time that the absence of LCAT attenuates the rise of apoB-containing lipoproteins in response to dietary cholesterol. No evidence of corneal opacities or renal insufficiency was detected in 4-month-old homozygous knockout mice. The availability of a homozygous animal model for human LCAT deficiency states will permit further evaluation of the role that LCAT plays in atherosclerosis as well as the feasibility of performing gene transfer in human LCAT deficiency states.

Animals↗
PubMed1997

Generation of free radicals during lipid hydroperoxide-triggered apoptosis in PC12h cells.

The compound 13-L-hydroperoxylinoleic acid (LOOH) triggered the death of clonal rat pheochromocytoma PC12h cells (LD50 = about 8 microM). LOOH induced nuclear condensation and DNA fragmentation, which was prevented by cycloheximide (a protein synthesis inhibitor) and NGF, indicating that LOOH triggered apoptosis in PC12h cells. LOOH produced reactive oxygen species (ROS) in PC12h cells in a time- and dose-dependent manner, as measured by flow cytometry using the ROS-specific fluorescent indicator, 6-carboxy-2,7-dichorodihydrofluorescein diacetate, di(acetoxymethyl ester) (C-DCDHF-DA). Antioxidants such as N,N'-diphenyl-p-phenylenediamine (DPPD), vitamin E and N-acetylcysteine, and a ferric iron chelator, deferoxamine, inhibited the LOOH-triggered apoptosis and simultaneously decreased the generation of ROS, whereas an inhibitor of glutathione synthesis, buthionine sulfoximine (BSO), enhanced the apoptosis and increased the generation of ROS. These results indicate that LOOH triggers the apoptosis of PC12h cells by increasing the production of ROS. A confocal analysis with the Ca(2+)-specific fluorescent indicator, fluo-3, demonstrated that LOOH at concentrations up to 200 microM, did not increase the intracellular Ca2+ concentration. These data indicate that LOOH induces apoptosis of PC12h cells through the enhanced production of ROS, not through increasing the permeability of Ca2+.

Animals↗