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Biomedical subjects

H Yasuda

Publications and source records attributed to H Yasuda.

At least 235 records · Page 13Linked to original sources
PubMed1998

Effects of the novel tricyclic quinoxalinedione derivatives, SM-18400 and its analogs, on N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in the isolated neonatal rat spinal cord in vitro.

We examined the effects of novel tricyclic quinoxalinedione derivatives, SM-18400 ((S)-9-chloro-5-[p-aminomethyl-o-(carboxymethoxy)phenylcarbamoylmethy l]-6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-dione hydrochloride trihydrate) and its analogs (i.e., ID-17263 and ID-17332), on the N-methyl-D-aspartate (NMDA) receptor-mediated polysynaptic reflex (PSR) in the isolated spinal cord of neonatal rats in vitro. Application of SM-18400 selectively suppressed the PSR activity in a concentration-dependent manner without affecting the monosynaptic reflex (MSR). Differential suppression of the PSR was also obtained with ID-17263, ID-17332 and other known NMDA receptor glycine-binding site antagonists, 5,7-dichlorokynurenate (5,7-diClkyn) and L-689,560 (4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4 -tetrahydroquinoline). Relative potencies of the test drugs for inhibition of the PSR were as follows: SM-18400 >> L-689,560 > ID-17332 > ID-17263 > 5,7-diClkyn. In addition, the inhibitory effects of SM-18400 on PSR were markedly antagonized by simultaneous application of D-serine, an agonist for NMDA receptor glycine-binding sites. These findings suggest that SM-18400 is a potent NMDA receptor glycine-binding site antagonist and blocks the NMDA receptor-mediated synaptic neurotransmission in the spinal cord in vitro.

Aminoquinolines↗
PubMed1998

(+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride) induces saliva and tear secretions in rats and mice: the role of muscarinic acetylcholine receptors.

We investigated effects of (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride), a rigid analogue of acetylcholine, on saliva and tear secretions in rats and mice to evaluate its therapeutical efficacy for xerostomia and xerophthalmia in patients with Sjogren's syndrome and X-ray exposure in the head and neck. Intraduodenal administrations of SNI-2011 increased saliva secretion in a dose-dependent manner at doses ranging from 3 to 30 mg/kg in normal rats and mice, two strains of autoimmune disease mice and X-irradiated saliva secretion defective rats. The salivation elicited by SNI-2011 was completely inhibited by atropine. A similar atropine-sensitive response was observed in tear secretion. In rat submandibular/sublingual gland membranes, [3H]quinuclidinyl benzilate (QNB) binding was saturable, and Scatchard plot analysis revealed a single population of binding sites with a Kd of 22 pM and a maximal binding capacity of 60 fmol/mg protein. The competitive inhibition curve of the [3H]QNB binding by SNI-2011 was obtained, and its dissociation constant value calculated from IC50 was 1-2 microM. These results suggest that SNI-2011 increases saliva and tear secretions through a direct stimulation to muscarinic receptors in salivary and lacrimal glands, and they suggest that SNI-2011 should be beneficial to patients with Sjögren's syndrome and X-ray exposure in the head and neck.

Animals↗
PubMed1998

Effects of the deleted form of hepatocyte growth factor on serum hyaluronate levels in rats with liver cirrhosis.

Effects of the deleted form of hepatocyte growth factor (dHGF) on serum hyaluronate levels, an index for liver cirrhosis, were studied in rats. The levels of serum hyaluronate increased in rats with dimethylnitrosamine- or carbontetrachloride-induced cirrhotic liver with prolongation of prothrombin time, which indicates disorder of liver function. Daily intravenous injection of dHGF reduced the elevated serum hyaluronate levels with improvement of the prolonged prothrombin time. These results suggest that the amelioration of hepatic function disorder by dHGF leads to a reduction of the increased serum hyaluronate levels.

Animals↗
PubMed1998

Neuropathy associated with angioimmunoblastic lymphadenopathy-like T-cell lymphoma.

A 75-year-old woman was admitted because of pain and numbness in the extremities and trunk. She subsequently suffered from lymphadenopathy and spiky fever. The immunohistochemical analysis of the biopsied lymph nodes and sural nerve and electrophysiological examination supported a diagnosis of angioimmunoblastic lymphadenopathy-like T cell lymphoma with polyneuropathy. The infiltrating lymphoma cells of the sural nerve and lymph node shared the same phenotype (CD45RO, CD3, CD30 positive). An increased expression of HLA-DR antigen was observed in endothelial and Schwann cells. Chemotherapy with CHOP-Bleomycin markedly relieved her pain. These findings suggest that a direct lymphocytic infiltration in the nerve may be associated with neuropathy in this case.

Aged↗
PubMed1998

Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.

Gene regulation in the cardiovascular tissues of diabetic subjects has been reported to be altered. To examine abnormal activities in transcription factors as a possible cause of this altered gene regulation, we studied the activity of two redox-sensitive transcription factors--nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1)--and the change in the mRNA content of heme oxygenase-1, which is regulated by these transcription factors in the cardiac tissues of rats with streptozotocin-induced diabetes. Increased activity of NF-kappaB and AP-1 but not nuclear transcription-activating factor, as determined by an electrophoretic mobility shift assay, was found in the hearts of 4-week diabetic rats. Glycemic control by a subcutaneous injection of insulin prevented these diabetes-induced changes in transcription factor activity. In accordance with these changes, the mRNA content of heme oxygenase-1 was increased fourfold in 4-week diabetic rats and threefold in 24-week diabetic rats as compared with control rats (P < 0.01 and P < 0.05, respectively). Insulin treatment also consistently prevented changes in the mRNA content of heme oxygenase-1. The oral administration of an antioxidant, probucol, to these diabetic rats partially prevented the elevation of the activity of both NF-kappaB and AP-1, and normalized the mRNA content of heme oxygenase-1 without producing any change in the plasma glucose concentration. These results suggest that elevated oxidative stress is involved in the activation of the transcription factors NF-kappaB and AP-1 in the cardiac tissues of diabetic rats, and that these abnormal activities of transcription factors could be associated with the altered gene regulation observed in the cardiovascular tissues of diabetic rats.

Animals↗
PubMed1998

Synthesis and structure-activity relationships of 1beta-methylcarbapenems with quaternary ammonium side chains.

The synthesis and antibacterial activity of 1beta-methylcarbapenems with quaternary ammonium groups at the C-2 position have been studied. Two types of new carbapenem derivatives have been synthesized. These 1beta-methylcarbapenems, one type having a (2S,4S)-2-[1,1-dimethyl-2-(1-piperazinyl)carbonyl]pyrrolidinio-4-+ ++ylthio group and the other type having a (2S,4S)-2-(4-carbamoylmethyl-4-methylhomopiperazinio-1-yl carbonyl)pyrrolidin-4-ylthio group, show potent and well balanced antibacterial activity as well as high stability against dehydropeptidase-I. The in vivo potency of these two carbapenems was compared with that of meropenem. The structure-activity relationships leading to these carbapenems are also described.

Animals↗
PubMed1998

[Priapism treated by caverno-glandular shunt, caverno-saphenous shunt and caverno-spongiosum shunt: report of a case].

A 44-year-old man visited a local urologist complaining of continuous pain and tumescence at penis persisting for 3 days. He was diagnosed with priapism. A caverno-glandular and caverno-saphenous shunt was performed. He presented to our hospital 3 days later, because the symptoms especially tumescence continued. We confirmed the diagnosis of low-flow priapism from cavernosography and intracavenal blood-gasometry and performed caverno-spongiosum shunt. Detumescence was finally achieved after the operation.

Adult↗
PubMed1997

Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53.

The tumor suppressor p53 is degraded by the ubiquitin-proteasome system. p53 was polyubiquitinated in the presence of E1, UbcH5 as E2 and MDM2 oncoprotein. A ubiquitin molecule bound MDM2 through sulfhydroxy bond which is characteristic of ubiquitin ligase (E3)-ubiquitin binding. The cysteine residue in the carboxyl terminus of MDM2 was essential for the activity. These data suggest that the MDM2 protein, which is induced by p53, functions as a ubiquitin ligase, E3, in human papillomavirus-uninfected cells which do not have E6 protein.

Amino Acid Sequence↗
PubMed1997

Long-lasting salivation induced by a novel muscarinic receptor agonist SNI-2011 in rats and dogs.

The sialogogic effect of SNI-2011, a novel muscarinic receptor agonist, (+/-)-cis-2-methylspilo [1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate, was compared with that of pilocarpine hydrochloride in a dose range in which the two muscarinic agonists exhibited approximately similar efficacy in eliciting salivation. Pilocarpine (0.66-2.0 mg/kg, i.d.) induced a marked but short-lasting salivation in rats, whereas the salivation induced by SNI-2011 (20-60 mg/kg, i.d.) lasted 1.4- to 1.8-fold longer. In dogs, the sialogogic effect of SNI-2011(1-3 mg/kg, i.v.) also lasted about 2-fold longer than that of pilocarpine (0.1-0.3 mg/kg, i.v.). The plasma SNI-2011 level that caused salivation at a rate of 0.4 ml/min was about 100 ng/ml and higher rates of salivation (over 0.4 ml/min) induced by 1 mg/kg SNI-2011 lasted for about 90 min in dogs. The plasma pilocarpine level that caused salivation at a rate of 0.4 ml/min was about 25 ng/ml and the higher rate of salivation (over 0.4 ml/min) induced by 0.1 mg/kg pilocarpine lasted only for 20 min in dogs. Effective plasma levels of SNI-2011 persisted longer than those of pilocarpine. These results indicate that SNI-2011 may be useful in the treatment of xerostomia because of its long-lasting sialogogic action.

Animals↗
PubMed1997

Beraprost sodium, an analogue of prostacyclin, induces the expression of mitogen-activated protein kinase phosphatase and inhibits the proliferation of cultured mesangial cells.

Beraprost sodium, an analogue of prostacyclin, increases intracellular cyclic adenosine monophosphate (cAMP) in cultured glomerular mesangial cells. We examined the effect of beraprost on mesangial cell proliferation. Beraprost was able to inhibit fetal bovine serum-stimulated proliferation of mesangial cells in concentrations enough to increase cellular cAMP. By northern blot analysis, beraprost induced the expression of MKP-1, a mitogen-activated protein kinase phosphatase, in a dose- and time-dependent manner, similarly to dibutyryl cAMP and adrenomedullin. These results indicate that beraprost inhibits the proliferation of mesangial cells and one of the mechanisms might be cAMP-dependent induction of MKP-1.

Animals↗
PubMed1997

Fission yeast Cut2 required for anaphase has two destruction boxes.

The fission yeast Schizosaccharomyces pombe cut2(+) gene is essential for sister chromatid separation. Cut2 protein, which locates in the interphase nucleus and along the metaphase spindle, disappears in anaphase with the same timing as mitotic cyclin destruction. This proteolysis depends on the APC (Anaphase-Promoting Complex)-cyclosome which contains ubiquitin ligase activity. The N-terminus of Cut2 contains two stretches similar to the mitotic cyclin destruction box. We show that both sequences (33RAPLGSTKQ and 52RTVLGGKST) serve as destruction boxes and are required for in vitro polyubiquitination and proteolysis. Cut2 with doubly mutated destruction boxes inhibits anaphase, whereas Cut2 with singly mutated boxes can suppress cut2 mutations. Strong expression of the N-terminal 73 residues containing the destruction boxes leads to the accumulation of endogenous cyclin and Cut2, and arrests cells in metaphase, whereas the same fragment with the mutated boxes does not. Cut2 proteolysis occurs in vitro using Xenopus mitotic extracts in the presence of functional destruction boxes. Furthermore, Cut2 is polyubiquitinated in an in vitro system using HeLa extracts, and this polyubiquitination requires the destruction boxes.

Anaphase↗
PubMed1997

14-3-3 zeta protein binds to the carboxyl half of mouse wee1 kinase.

To identify proteins which bind to mouse wee1 kinase, the yeast "two-hybrid" system was used with a mouse cDNA library. Using the carboxyl half of weel kinase, the 14-3-3 zeta protein was isolated. Recombinant 14-3-3 zeta was demonstrated to bind to wee1 kinase in vitro. The wee1 kinase phosphorylated by cdc2 kinase also bound to 14-3-3 zeta protein. When both wee1 kinase and 14-3-3 zeta were transfected into COS-1 cells, they formed a complex in a cell. The sequence of wee1 kinase necessary for the binding was tested by a two hybrid system expressing different lengths of peptides derived from wee1 kinase. Both the entire kinase domain and a sequence in the carboxyl terminus was thought to be necessary for the binding. The function of 14-3-3 zeta protein remained to be elucidated in relation to the regulation of G2 to M phase transition through wee1 kinase.

14-3-3 Proteins↗
PubMed1997

Preparation of Copolymer Particles of Styrene with N-Vinylimidazole-Metal Complexes

The preparation of fine copolymer particles of N-vinylimidazole-metal complexes with styrene by emulsifier-free emulsion polymerization was investigated. Monodisperse spherical particles were formed in low concentrations of monomers. Significant amounts of Co and Ni were introduced into the copolymer particles. The amounts of Co incorporated into the particles are higher than those of Ni.

Journal Article↗
PubMed1997

CD8 cytotoxic T-cell clone rapidly transfers autoimmune diabetes in very young NOD and MHC class I-compatible scid mice.

A CD8 T-cell clone (YNK1.3) generated from acutely diabetic NOD mouse islets, showed proliferation and cytotoxicity when challenged with NOD and BALB/c islet cells and NOD-derived insulinoma cells. When 1-2 x 10(7) YNK1.3 cells were administered to 7-10-day-old NOD mice, the cells transferred overt diabetes very rapidly in each of the 16 recipients within 4 days of cell transfer. However, of 14 recipients receiving YNK 1.3 cells above 14 days of age none became diabetic. Fluorescent dye-labelled YNK1.3 cells extensively accumulated in the islets by 36 h after transfer in 7-day-old NOD recipients, while no significant insulitis was seen in 21-day-old recipients. Over half of NOD-scid recipients (5/9) rapidly became diabetic within 5 days after transfer of 1-2 x 10(7) YNK1.3 cells at 7 days of age, whereas only one of 12 recipients over 14 days of age became diabetic. Furthermore, YNK1.3 cells also transferred diabetes to H-2Kd-matched very young BALB/c-scid and CB17-scid mice, but not to C57BL/6-scid mice. Thus, optimally activated islet-specific CD8 T-cell clones are able to rapidly transfer diabetes to NOD and MHC class I compatible scid mice when a large enough number is administered at 7 days of age. Administration of monoclonal antibodies against adhesion molecules involved in the trafficking of lymphocytes from the circulation into the inflammatory tissues, could not prevent the cellular infiltration of YNK1.3 cells into the islets in 7-day-old NOD recipients. The results indicate that islet cells in the mouse around 7 days of age are generally susceptible to cytotoxic CD8 T cells, suggesting, therefore, that CD8 T cells may play an important role in the initiation of autoimmune diabetes in NOD mice.

Adoptive Transfer↗
PubMed1997

Suppression of mouse contact hypersensitivity after treatment with antibodies to leukocyte function-associated antigen-1 and intracellular adhesion molecules-1.

We investigated the effects of the antibodies against the adhesion molecules leucocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) on mouse allergic contact hypersensitivity. Mice were injected intraperitoneally with both antibodies before sensitization by an epicutaneous application of dinitrofluorobenzene (DNFB). Simultaneous administration of the antibodies induced suppression of ear swelling in the effector phase of contact hypersensitivity. To show the effect of antibodies in vitro, lymph node cells (LNC) of mice treated with antibodies or with phosphate-buffered saline (PBS) were cultured in the presence of dinitrobenzene sulphonic sodium salts (DNBS), and the production of interleukin-2, interleukin-4 and interleukin-10 in the culture supernatants was measured using an enzyme-linked immunosorbent assay (ELISA). It was found that the production of interleukin-2 in the cells of mice treated with the antibodies was significantly lower than in the cells of PBS-treated mice. On the other hand, no difference was noted in the production of interleukin-4 or interleukin-10. Our results indicate that in vivo simultaneous administration of antibodies to cell adhesion molecules before hapten sensitization induces the suppression of contact hypersensitivity in mice and that the suppression may be due to the inhibition of the production of interleukin-2.

Animals↗
PubMed1997

Selective depression of the spinal polysynaptic reflex by the NMDA receptor antagonists in an isolated spinal cord in vitro.

1. The effects of N-methyl-D-aspartate (NMDA) receptor glycine-binding site antagonists 7-chlorokynurenate (7-Clkyn) and (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966) on spinal reflexes in an isolated spinal cord that was maintained in Mg(2+)-free medium in vitro were examined. The actions of 7-Clkyn and HA-966 were compared with those of the channel-site antagonist (i.e., dizocilpine) and NMDA-binding site antagonists--that is, 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (CPP) and DL-2-amino-5-phosphonovalerate (APV). 2. 7-Clkyn and HA-966 produced a selective depression of the polysynaptic reflex (PSR) while negligibly affecting the activity of the monosynaptic reflex (MSR). The PSR was also differentially suppressed by dizocilpine, CPP and APV. The PSR inhibitory activity of the NMDA antagonists was in the following order: dizocilpine > CPP > APV = 7-Clkyn > HA-966. 3. The inhibitory effects of 7-Clkyn on PSR were markedly antagonized by the simultaneous application of D-serine, an agonist for the NMDA receptor glycine-binding sites. However, PSR inhibition by dizocilpine and CPP was unaffected. 4. Inhibition of the PSR by 7-Clkyn persisted in the presence of strychnine, which markedly increased the PSR activity by itself. 5. These findings suggest that the NMDA receptor glycine-binding sites play a role in generating the NMDA receptor-mediated PSR in the spinal cord in vitro.

Animals↗