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T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 307 records · Page 17Linked to original sources
PubMed1998

c-Fos induces apoptosis in germinal center B cells.

We examined the role of c-Fos in the differentiation of mature B cells into IgG-producing cells using transgenic mice carrying the c-fos gene under the control of the IFN-alpha/beta-inducible Mx promoter (Mx-c-fos) or the constitutive H-2Kb promoter (H2-c-fos). Splenic B cells from Mx-c-fos mice were cultured with LPS and rIL-4, and IgG1+ B cells were developed in the culture after day 3. When IFN-alpha/beta was added to the culture from day 2, development of IgG1+ B cells was perturbed, and the number of apoptotic cells increased within 24 h, suggesting that c-Fos induces apoptosis in Ig class-switching B cells. To confirm the effect of c-Fos on B cell differentiation in vivo, H2-c-fos mice were immunized with DNP-OVA. The mice produced primary IgM, but not IgG, anti-DNP Ab in serum and failed to generate germinal centers in spleen. The perturbation of germinal center formation in H2-c-fos mice was rescued by mating them with transgenic mice carrying the bcl-2 gene with the Ig promoter. However, primary IgG1 anti-DNP Ab production was still suppressed in doubly transgenic mice, suggesting that Bcl-2 can delay the time of c-Fos-induced apoptosis in Ig class-switching B cells but cannot rescue the death. Since c-Fos is induced in mature B cells reacted with Ags, and clonal deletion of self-reactive B cells in germinal centers is insensitive to Bcl-2, these results suggest that c-Fos plays a causal role in clonal deletion of germinal center B cells.

Animals↗
PubMed1998

Neonatal primary neuronal death induced by capsaicin and axotomy involves an apoptotic mechanism.

To clarify the mechanism of capsaicin-induced primary neuronal cell death, newborn and adult rats were given a subcutaneous injection of capsaicin (50 mg/kg). Neonatal capsaicin injection induced neuronal apoptosis in the trigeminal ganglion. Apoptotic neurons had peripheral stacks of long parallel endoplasmic reticulum that are characteristic to primary neurons of the B-type, and exhibited nucleoplasmic condensation, nuclear shrinkage and cytoplasmic fragmentation. Light microscopically, apoptotic neurons exhibited a sign of DNA fragmentation as revealed by a nick end labelling method. The proportion of apoptotic cells was quite low during the first 12 h after capsaicin injection (<1%), rapidly increase to 10.44% by 24 h, and decreased to 0.29% by 48 h. Normal and vehicle control levels of apoptosis were <1%. Nerve growth factor (NGF, 0.5 mg/kg) simultaneously administered with capsaicin reduced the incidence of apoptosis by about 35% at 24 h post-injection. Neonatal transection of the infraorbital nerve induced neuronal apoptosis similar to that produced by the neonatal capsaicin in the maxillary division of the trigeminal ganglion. Unlike capsaicin, however, the neurotomy-induced apoptosis was seen in neurons of both the A- and B-types. Neither the capsaicin injection nor the neurotomy induced apoptosis in adult rats, though mitochondrial swelling similar to that seen at 0.5 h after neonatal capsaicin was observed after capsaicin injection in adults. The results indicate that the capsaicin-induced and nerve injury-induced primary neuronal damages in newborn rats share a common final pathway, apoptosis.

Animals↗
PubMed1998

Shape Control of Monodisperse Hematite Particles by Organic Additives in the Gel-Sol System.

It has been found that not only inorganic anions such as sulfate and phosphate, but also organic reagents such as dihydroxybenzenes, dihydroxynaphthalenes, ethylenediamine tetraacetic acid (EDTA), and nitrilotriacetic acid (NTA) can be used as a shape controller for forming ellipsoidal hematite (alpha-Fe2O3) particles in the gel-sol system. Specifically, this paper focuses on the formation process of monodisperse ellipsoidal hematite particles with hydroxybenzenes. Interestingly, while 1,3-dihydroxybenzene had no effect on the shape of hematite, 1,4- and 1,2-dihydroxybenzenes could produce ellipsoidal particles. However, 1,4-dihydroxybenzene (hydroquinone) itself turned out to have no ability of adsorption to hematite. It was finally concluded that hydroquinone was oxidatively polymerized to form a kind of humic compound during aging at 100 degreesC for the growth of hematite particles, controlling the anisotropic growth by adsorption of the polymerized species. In addition, a considerable amount of the adsorbed polymer was found to be retained in the internal grain boundaries of the subcrystals, as revealed from XPS, XRD, and FT-IR analyses. Lastly, the mechanism of shape control by 1,2-dihydroxy-3,5-benzenedisulfonic acid disodium salt (Tiron) which is directly adsorbed to growing hematite particles is also discussed. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors.

The peptide nociceptin (also named orphanin FQ) acts in the brain to produce various pharmacological effects, including hyperalgesia and hypolocomotion. The nociceptin receptor uses guanine-nucleotide-binding proteins to mediate the inhibition of adenylyl cyclase, the activation of potassium channels and inhibition of calcium channels. It has been shown using knock-out mice that the nociceptin receptor is not required for regulation of nociceptive responses or locomotion activity, but modulates the auditory function. Here we show that mice lacking the nociceptin receptor possess greater learning ability and have better memory than control mice. Histological analysis revealed the expression of both the nociceptin precursor and the nociceptin receptor in the hippocampus, thought to take part in aspects of learning and memory. Moreover, the receptor-deficient mice showed larger long-term potentiation in the hippocampal CA1 region than control mice, without apparent changes in presynaptic or postsynaptic electrophysiological properties. These results show that the loss of the nociceptin receptor results in a gain-of-function mutation in both the memory process and the long-term potentiation mechanism in CA1, perhaps as a result of altered intracellular signal transduction systems in neurons.

Animals↗
PubMed1998

Papid Growing Fibroadenoma in an Adlescent.

INTRODUCTION: We report a case of rapidly growing fibroadenoma. PATIENT: A 13-year-old girl consulted the outpatient clinic regarding a left breast mass. The mass was diagnosed as fibroadenoma by clinical examinations, and the patient was carefully monitored. The mass enlarged rapidly with each menses and showed a 50% increase in volume four months later. Lumpectomy was performed. The tumor was histologically diagnosed as fibroadenoma organized type and many glandular epithelial cells had positive immunohistochemical staining for anti-estrogen receptor antibody in the nuclei. CONCLUSION: The estrogen sensitivity of the tumor could account for the rapidgrowth.

Journal Article↗
PubMed1998

A Theoretical Analysis of Sea-anchor Soaring.

This study presents a concise mathematical model that accounts for sea-anchor soaring, a special flight technique used by sea birds, in particular storm petrels. Conventional wing theory is used to reveal the mechanics of sea-anchor soaring. The feasibility and existence of an equilibrium are summarized by formulae giving the wind velocity criteria. The stability of the equilibrium is also revealed: among two possible equilibria, the equilibrium at the very low velocity to water is shown to be stable. Numerical examples show the following: sea-anchor soaring is almost always stable; Wilson's storm petrel can soar at 0.256 ms-1 in wind with 4.79 ms-1 under the best conditions. Larger sea-birds like albatrosses need gusty winds to soar, but such strong winds make the sea choppy and hence prevent soaring. Foot-web size regulates the size of a bird utilizing sea-anchor soaring at low velocities to water.Copyright 1998 Academic Press Limited

Journal Article↗
PubMed1998

Induction of immediate-early genes c-fos and zif268 in the subnucleus oralis by noxious tooth pulp stimulation.

c-fos and zif268 expression were assessed by immunocytochemistry for c-Fos and Zif268 proteins in the sensory trigeminal nuclear complex following noxious mechanical stimulation of the mandibular incisor pulp of rats. Marked up-regulation of both immediate early genes was observed in the subnucleus oralis ipsilateral to the stimulation. Cavity preparation of the dentine without reaching the pulp did not cause significant up-regulation detectable by immunocytochemistry. These results provide evidence that noxious dental signals reach the ipsilateral subnucleus oralis and up-regulate the transcription of immediate early genes c-fos and zif268.

Animals↗
PubMed1998

Diurnal change of the cold-inducible RNA-binding protein (Cirp) expression in mouse brain.

RNA-binding proteins are believed to play important roles in regulation of neural functions. Recently, a mouse cDNA encoding the cold-inducible RNA-binding protein, Cirp, has been isolated, the amino acid sequence of which showed similarity to plant circadian rhythm proteins. In the present study, diurnal expression of Cirp in the mouse nervous system was examined. Northern blot analysis showed that the level of Cirp mRNA was diurnally regulated in the brain but not in the testis and liver. The level increased during the daytime and decreased during the nighttime. Immunohistochemistry using an anti-Cirp antibody showed that Cirp was expressed in the nucleus of neurons and that the level of Cirp was diurnally regulated in the suprachiasmatic nucleus and the cerebral cortex. The diurnal regulation was not observed in the brain of adult mice kept in constant darkness nor that of 3-day-old mice. These findings suggest that Cirp plays a role in biological rhythms as known for plant proteins and that expression of Cirp is regulated differentially in discrete brain regions.

Animals↗
PubMed1998

Hydrogen peroxide induces up-regulation of Fas in human endothelial cells.

Hydrogen peroxide (H2O2), an oxidant generated by inflammatory cells, is an important mediator of injury of endothelial cells (ECs). Here we show that H2O2 induces up-regulation of the expression of Fas, a death signal, in human ECs in culture. Flow cytometric analysis with a mAb against human Fas showed that incubation for 24 h with H2O2 induced a dose-dependent increase in the level of Fas in ECs. Coincubation with catalase, which rapidly degrades H2O2, inhibited H2O2-induced up-regulation of Fas. H2O2 also induced a dose-dependent increase in Fas mRNA level. A significant increase in Fas mRNA levels was observed from 6 h after stimulation with H2O2. Vanadate, a protein phosphatase inhibitor, significantly enhanced Fas mRNA and protein levels in H2O2-treated ECs. On the other hand, genistein, a tyrosine kinase inhibitor, inhibited H2O2-induced Fas mRNA expression. Furthermore, a flow cytometric method with propidium iodide staining and electron microscopic analysis showed that incubation with an agonistic Ab against Fas (anti-Fas IgM) induced apoptosis in H2O2-treated cells. These findings suggest that H2O2 induces up-regulation of Fas in ECs and that activation of protein tyrosine kinase may be involved in the mechanism of H2O2-induced Fas expression. Therefore, Fas-mediated apoptosis may have a pathologic role in H2O2-induced EC injury and thereby provide a new therapeutic target.

Apoptosis↗
PubMed1998

The kinase suppressor of Ras (KSR) modulates growth factor and Ras signaling by uncoupling Elk-1 phosphorylation from MAP kinase activation.

The Ras GTPase plays an essential role in many cellular signal transduction events. Activation of the mitogen activated protein (MAP) kinase is a primary consequence of Ras activation and plays a key role in mediating Ras signal transduction. A novel kinase, KSR, has recently been functionally isolated as a positive regulator of Ras signaling in Caenorhabditis elegans vulval induction and Drosophila photoreceptor differentiation. We have examined the effect of KSR on growth factor and Ras-induced MAP kinase signaling in mammalian cells. Surprisingly, we observed that KSR specifically blocks EGF and Ras-induced phosphorylation and activation of ternary complex factors (TCF), physiological substrates of MAP kinases, without affecting the activation of MAP kinase itself. A kinase-deficient mutant of KSR, KSR-RM, appears to function as a dominant interfering mutant which elevates phosphorylation of Elk-1, a member of the TCF family, and Elk-1-dependent transcription. The effect of KSR on Elk-1 was significantly decreased by inhibition of calcineurin, a putative Elk-1 phosphatase. These observations demonstrate that KSR is capable of uncoupling the MAP kinase activation from its target phosphorylation, and thus provide a novel mechanism for modulating the Ras-MAP kinase signaling pathway. This study provides the first evidence that signal output of MAP kinase cascades is subject to regulation at a level independent of MAP kinase activity.

3T3 Cells↗
PubMed1998

c-fos induction in the subnucleus oralis following trigeminal nerve stimulation.

Neurons with c-Fos protein-like immunoreactivity (fos-neurons) were examined in the rostral parts of the brainstem sensory trigeminal nuclear complex following intense electrical stimulation of the trigeminal nerves and noxious mechanical stimulation of the trigeminal receptive fields. Stimulation of all the examined nerves and receptive fields induced some fos-neurons at the medial edge of the subnucleus interpolaris but not in the principal sensory trigeminal nucleus. Stimulation of the primary neurons innervating the intraoral structures but not facial skin induced fos-neurons in the ipsilateral subnucleus oralis. These oralis fos-neurons were located in the dorsomedial nucleus that contained calcitonin gene-related peptide-like immunoreactivity. The oralis fos-neurons are considered to be involved in the processing of intraoral nociceptive signals.

Analysis of Variance↗
PubMed1998

Percutaneous isolated liver chemoperfusion for treatment of unresectable malignant liver tumors: technique, pharmacokinetics, clinical results.

We have developed a single-catheter technique for percutaneous isolated liver chemoperfusion (PILP) with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) for the treatment of malignant liver tumors. We report here the surgical technique, pharmacokinetics, and effectiveness of PILP in multiple advanced liver tumors. Twenty-eight patients with hepatocellular carcinoma (HCC) and 18 with metastatic liver tumors underwent a total of 61 PILPs with HVI-CHP. HVI-CHP was accomplished mainly by the single-catheter technique using a novel four-lumen, two-balloon catheter; it was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. Under HVI-CHP, either doxorubicin 960-150 mg/m2) or cisplatin (150-200 mg/m2) was infused via the hepatic artery. The PILP was completed successfully in all 61 trials. Two of forty-six patients died early; one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Excluding these two deaths, the treatments were well tolerated. The major side effects were mild to moderate chemical hepatitis and reversible myelosuppression. Of the 27 evaluable HCC patients, 17 (63%) had an objective tumor response (5 complete and 12 partial responses). In 15 patients with colorectal hepatic metastases (CHM), 7 had a sharp decrease in serum carcinoembryonic antigen (CEA) levels (to < 50% of their pretreatment levels) after treatment. However, a single PILP had limited efficacy in terms of the durability of remission (< or = 6 months in most CHM patients, as assessed by CEA levels). These results indicate that PILP with HVI-CHP has high efficacy in most patients with multiple advanced liver tumors. In addition, the results suggest a role of multiple treatment courses of PILP in the induction of long-term remission, especially for patients responsive to the first treatment.

Antineoplastic Agents↗
PubMed1998

Successful surgical treatment of an Edwards type IIIB right aortic arch aneurysm: report of a case.

A true aneurysm of the right aortic arch which accompanies various branching characteristics is very rare. We report herein the successful surgical treatment of an elderly patient found to have an Edwards type IIIB right aortic arch aneurysm encircling and compressing the trachea. The complete right aortic arch and right subclavian artery were reconstructed through the inside of the aneurysm using selective cerebral perfusion. The patient recovered well, with no residual neurologic deficit and with resolution of the dyspnoic attacks he had suffered preoperatively.

Aortic Aneurysm, Thoracic↗
PubMed1998

Repeat tricuspid valve replacement for acquired valvular heart disease: report of a case.

A patient was admitted to our hospital for investigation of exertional dyspnea and liver dysfunction, 10 years after undergoing mitral valve replacement (MVR) and tricuspid valve replacement (TVR) using a Bjork-Shiley mechanical valve and a Carpentier-Edwards bioprosthesis, respectively. Echocardiographic examinations, magnetic resonance imaging (MRI), and cardiac catheterization subsequently revealed severe degenerative changes of the artificial tricuspid valve. Thus, a repeat TVR with plication of his enlarged right atrium that was compressing the right lung was performed. The extracorporeal circulation was adjusted so that the oxygen saturation of the hepatic vein was maintained above 50% to prevent liver damage. The patient had a good postoperative course and has encountered no further problems since his discharge from hospital.

Female↗
PubMed1998

[Spontaneous splenic rupture after mitral valve replacement for infective endocarditis].

We report a successful treatment of massive bleeding due to spontaneous splenic rupture after mitral valve replacement. A 61-year-old man was admitted to our hospital for intermittent high fever. An echocardiogram demonstrated a large vegetation on the posterior cusp of the mitral valve and mitral regurgitation of moderate degree. Staphylococcus epidermidis was cultured from his arterial blood. He underwent a mitral valve replacement after 3 weeks of antimicrobiological therapy with penicillin G crystalline and minocycline hydrochloeide. The patient fell into hemorrhagic shock on postoperative day 11 after complaining dull pain on his left upper abdomen for 3 days. A computed tomography demonstrated a splenic rupture and massive hematoma in the retroperitoneum. A splenic arterial embolization was done before splenectomy. The blood and clot of 2800 g were sucked from peritoneal and retroperitoneal cavities. There were no mycotic aneurysms nor abscess but the torn capsule on the swelled and partially necrotic spleen. The patient discharged uneventfully on postoperative day 43. Infective endocarditis frequently causes splenic infarction but rarely splenic rupture. Anticoagulation therapy after mitral valve replacement might have emphasized the bleeding in the patient.

Endocarditis, Bacterial↗
PubMed1998

Pharmacological characterization of YM087, a potent, nonpeptide human vasopressin V1A and V2 receptor antagonist.

The effects of YM087 (4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d] [1]benzazepin-6-yl)-carbonyl]-2-phenylbenzanilide monohydrochloride), a novel nonpeptide vasopressin (AVP) receptor antagonist, on [3H]AVP binding to human AVP receptors (V1A, V1B and V2) cloned and transiently expressed in COS-1 cells generated from monkey renal tissue were studied. Scatchard analysis of saturation isotherms for the specific binding of [3H]AVP to membranes, prepared from COS-1 cells transfected with human V1A, V1B and V2 receptors, yielded an apparent equilibrium dissociation constant (Kd) of 0.67 nM, 0.28 nM and 2.14 nM and a maximum receptor density (Bmax) of 2180 fmol/mg protein, 369 fmol/mg protein and 2660 fmol/mg protein, respectively. YM087 showed high affinity for AVP V1A and V2 receptors with Ki values of 6.3 and 1.1 nM, respectively, but had no effect on [3H]AVP binding to AVP V1B receptors. In COS-1 cells expressing either AVP V1A or V1B receptors, AVP caused a concentration-dependent increase in intracellular Ca2+ concentration ([Ca2+]i). YM087 inhibited the AVP-induced increase in [Ca2+]i in COS-1 cells expressing AVP V1A receptors in a concentration-dependent manner with an IC50 value of 14.3 nM, but did not influence this increase in AVP V1B-receptor expressing cells. In contrast, stimulation of COS-1 cells expressing AVP V2 receptors resulted in an accumulation of cAMP. YM087 inhibited AVP-induced cAMP production in COS-1 cells expressing AVP V2 receptors in a concentration-dependent manner with an IC50 value of 1.95 nM. In all assays used, YM087 was devoid of any agonistic activity. These results suggest that YM087 is a potent nonpeptide dual human AVP V1A and V2 receptor antagonist, and that YM087 will be a powerful tool in investigation of the physiological and pathophysiological roles of AVP.

Animals↗