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Biomedical subjects

T Arima

Publications and source records attributed to T Arima.

At least 91 records · Page 5Linked to original sources
PubMed1997

Tolerance to heart and kidney grafts induced by nondepleting anti-CD4 monoclonal antibody (RIB 5/2) versus depleting anti-CD4 monoclonal antibody (OX-38) with donor antigen administration.

BACKGROUND: The monoclonal antirat CD4 antibody RIB 5/2 has been shown to modulate the CD4 glycoprotein without eliminating the affected T cells. We have shown that the administration of multiple doses of RIB 5/2 during the peritransplantation period prevents the rejection of rat kidney allografts. METHODS: We compared the efficacy of a single intraperitoneal dose of 20 mg/kg RIB 5/2 plus donor antigen (25 x 10(6) spleen cells [SCs]) given by either an intrathymic or an intravenous route with the depleting anti-CD4 monoclonal antibody (mAb) OX-38 plus antigen 21 days before a major histocompatibility complex (MHC)-mismatched Lewis (RT1l) to Buffalo (RT1b) rat cardiac or renal allograft. By delaying the transplantation for 21 days, recovery from the nonspecific effects of the antibody treatment allowed the demonstration of donor antigen-specific tolerance. RESULTS: OX-38 mAb given with intrathymic SCs induced tolerance to heart but not kidney grafts, whereas OX-38 given with intravenous SCs failed to prolong survival of either heart or renal allografts. In contrast, RIB 5/2 mAb administration, when combined with alloantigen given by either intravenous or intrathymic routes, induced tolerance to heart allografts, whereas only alloantigen given by the intravenous route with RIB 5/2 resulted in tolerance to renal grafts. CONCLUSIONS: Concomitant administration of intravenous donor alloantigen and the modulation of CD4+ recipIent cells by nondepleting RIB 5/2, rather than elimination of these CD4+ cells with depleting mAb OX-38, is a more potent method for the induction of allograft tolerance.

Animals↗
PubMed1997

Association of IGF2 and H19 imprinting with choriocarcinoma development.

We studied IGF2 and H19 expression, and methylation status of H19 gene in androgenetic moles and choriocarcinomas. The human placentae were examined similarly as a control. The CpG sites analyzed for methylation covered the 5' portion and the entire coding regions of H19. Although the paternal IGF2 and the maternal H19 allele were exclusively transcribed in full-term placentae, both H19 alleles were active in early placentate of 6-8 weeks gestation. The level of H19 expression in the mole was similar to that in normal placentae, which is compatible with the finding that half of the H19 gene was methylated and the remaining one was hypomethylated en masse in the complete mole. These imply the importance of regulating the level of H19 transcription not only for normal embryogenesis but also for the development of androgenetic moles. Choriocarcinomas were characterized by a low expression of IGF2 and a high expression of H19 with the transcripts being apparently intact in size. Biallelic expression of IGF2 or H19 was found frequently but not consistently in choriocarcinomas. Contrary to expectation, enhanced H19 expression was accompanied by hypermethylation of CpG sites over the entire gene region, apparently being at variance with the finding in normal placentae and androgenetic moles. The hypermethylation of CpG sites was also recognized in choriocarcinoma specimens surgically removed. The active H19 allele was unmethylated in placentae and probably so in androgenetic moles, but it was heavily methylated in choriocarcinomas. These findings provide the possibility that the mutated promoter is responsible for overcoming transcriptional suppression by CpG methylation in the H19 gene.

Blotting, Southern↗
PubMed1997

Identification of interleukin-6 producing fibroblastoid cells in cerebrospinal fluid from patients with leukemic meningitis.

Cytokine producing native cells in cerebrospinal fluid (CSF) have not been identified. So, we investigated the cytokine producing ability of floating cells in CSF from patients with leukemic meningitis. Morphologic study revealed that established cell lines were polygonal or elongated in shape and had an abundant and irregular branched cytoplasm. Immunocytochemical analysis demonstrated positive reactivity with monoclonal anti-fibroblast antibody only. Interleukin-6 (IL-6) was constitutively produced in vitro by these cell lines; both interleukin-1 and lipopolysaccharides significantly increased its synthesis. These findings imply that these fibroblastoid cells are floating in CSF of patients with leukemic meningitis and produce IL-6 in response to various inflammatory stimulations in vivo.

Adult↗
PubMed1997

Alterations in acetylcholine, NMDA, benzodiazepine receptors and protein kinase C in the brain of the senescence-accelerated mouse: an animal model useful for studies on cognitive enhancers.

The senescence-accelerated mouse (SAMP8) is a useful murine model of accelerated aging and learning deficiency. We examined bindings of [3H]pirenzepine, [3H]dizocilpine (MK-801), [3H]flunitrazepam, [3H]8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and [3H]phorbol 12,13-dibutylate (PDBu) in SAMP8 brains, and compared them to those of SAMR1 (control). In the hippocampus of SAMP8 at 12 months, bindings of [3H]pirenzepine, [3H]MK-801, [3H]flunitrazepam, [3H]8-OH-DPAT and [3H]PDBu were significantly lower than those in SAMR1. In the cerebral cortex, bindings of [3H]pirenzepine, [3H]flunitrazepam and [3H]8-OH-DPAT were higher in SAMP8 than in SAMR1 at 12 months. [3H]PDBu binding was decreased in both the fractions of the membrane and cytosol in the hippocampus of SAMP8. The neurochemical findings presented here support behavioral and pharmacological findings that SAMP8 is a useful model of learning dysfunction and anxiety-deficiency. The usefulness of SAMP8 in studies on cognitive enhancers is also discussed.

Aging↗
PubMed1997

5-Hydroxytryptamine-induced Ca2+ -independent cGMP formation is mediated by nitric oxide in a nitric oxide synthase-independent manner in NG108-15 cells.

A novel pathway of 5-hydroxytryptamine (5-HT)-induced cGMP formation, which does not require Ca2+ and is distinct from the 5-HT, receptor-mediated pathway, is reported to exist in NG108-15 cells. Although the possible involvement of undefined 5-HT receptors and membrane-bound guanylyl cyclase is suggested. the mechanism is not clarified in detail in this Ca2+ -independent cGMP formation. In the present study, we investigated the activation mechanism of guanylyl cyclase activity. 5-HT-induced Ca2+ -independent cGMP formation was not observed in the cell membrane preparation. In intact cells, the 5-HT-induced Ca2+ -independent cGMP formation was inhibited by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazolin-1-oxyl 3-oxide (carboxyPTIO), a nitric oxide (NO)-specific trapper, and by 3,7-bis(dimethylamino)-phenothiazinium chloride (methylene blue), a cytosolic guanylyl cyclase-specific inhibitor, suggesting the involvement of NO and cytosolic guanylyl cyclase. Ca2+ -independent cGMP formation was not inhibited by 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA-AM), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), and various arginine-derivative nitric oxide synthase (NOS) inhibitors. Our findings suggest that 5-HT stimulation results in the generation of NO followed by cGMP formation in an NOS-independent manner in NG108-15 cells.

Animals↗
PubMed1997

Effects of kyotorphin (L-tyrosyl-L-arginine) ON[3H]NG-nitro-L-arginine binding to neuronal nitric oxide synthase in rat brain.

L-Tyrosyl-L-arginine (kyotorphin) is known as an endogenous analgesic neuropeptide. We examined whether kyotorphin and other arginine-containing neuropeptides were endogenous substrates for neuronal nitric oxide synthase (NOS) in the rat brain. Cytosol fractions of the rat cerebellum contained higher concentrations of neuronal NOS (nNOS) than endothelial NOS. In rat cerebellar cytosol, the binding activity of [3H]NG-nitro-L-arginine (NNA) was inhibited equally by L-arginine (L-Arg), kyotorphin, and L-leucyl-L-Arg (a kyotorphin receptor antagonist). Binding activities were inhibited to lesser degrees by fibronectin active fragments, bradykinin, and dynorphin A, but were not inhibited by L-tyrosyl-D-Arg or substance P. Interestingly, the inhibition of [3H]NNA binding by kyotorphin was attenuated by inhibitors of kyotorphin-hydrolyzing peptidases (KTPases) such as bestatin and arphamenine B. These results suggest that kyotorphin is degraded to L-Arg by KTPases, which in turn may act as substrate for nNOS.

Animals↗
PubMed1997

NG-nitro-L-[3H]arginine binding properties of neuronal nitric oxide synthase in rat brain.

NG-Nitro-L-arginine (L-NNA), a derivative of L-arginine (L-Arg), is known as a pseudosubstrate and inhibitor for nitric oxide synthase (NOS). To clarify the regulatory mechanism of substrate-binding domain in neuronal NOS (nNOS), we examined the characteristics of NG-nitro-L-[3H]Arg (L-[3H]NNA) binding using the cytosolic fraction and purified nNOS from the rat cerebellum, in comparison with L-[14C]citrulline formation from L-[14C]Arg. The L-[3H]NNA binding was inhibited by L-NNA > NG-methyl-L-Arg > diphenyleneiodonium > L-Arg, but was not inhibited by L-citrulline and D-Arg. Thus, L-NNA seems to bind the substrate-binding domain in the nNOS with high affinity rather than L-Arg. Even in the absence of NADPH, tetrahydrobiopterin (BH4) and Ca2+, the L-[3H]NNA binding activity was observed in the cerebellar cytosol, although L-[14C]citrulline could not be produced from L-[14C]Arg. L-[3H]NNA binding was increased by BH4 alone and was markedly enhanced by NADPH plus BH4 (NADPH/BH4), but not by Ca2+/CaM. In contrast, L-[14C]citrulline was formed only in the presence of NADPH/BH4 and Ca2+. Similar results were obtained in purified nNOS. These results suggest that L-[3H]NNA seems to bind the substrate-binding domain in the nNOS but the binding affinity of L-Arg was lower than the affinity of L-NNA. Although the substrate binding is necessary to BH4 and NADPH, Ca2+/CaM are further necessary for the formation of NO and L-citrulline.

Animals↗
PubMed1997

[Ameliorating effects of dan-shen and its major ingredient calcium/magnesium lithospermate B on cognitive deficiencies in senescence-accelerated mouse].

Effect of the long-term treatment with a Dan-Shen (Salviae miltiorrhizae radix) methanol extract (DME) or its major ingredient lithospermate B (LSB) on memory and learning in scenescence-accelerated mouse (SAM) was investigated by means of Morris's water maze task. DME or LSB treatment significantly decreased the escape latency in the P8 strain of SAM (SAMP8), which strain spontaneously develops learning deficits. These results suggest that DME and LSB treatment improved spacial learning. Neurochemical investigations indicated that both drugs did not affect the cholinergic system, but enhanced functions of the glutamate-PKC system in hippocampus, since the increases in [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]-cyclohepten-5,10-imine maleate) binding in cortex and [3H]PDBu (phorbol 12,13-dibutyrate) binding in hippocampus were observed in DME and LSB treatments. Our previous studies indicate the decrease in PDBu binding and NMDA receptor-mediated functions in SAMP8 brain. Thus, it is suggested that 1) Methanol extract of Dan-Shen is effective for prevention of spacial learning deficit caused with aging, 2) lithospermate B is one of the active ingredients, 3) SAMP8 is useful model animal to investigate drugs for anti-aging or anti-dementia.

Aging↗
PubMed1997

An innovative method using the Leeds-Keio artificial ligament in the unstable spine.

We have designed two innovative surgical procedures using the Leeds-Keio artificial ligament to solve the difficult problems caused by the difference in physical properties between bone structure and spinal implants, such as pedicle screw systems, used for treating the unstable lumbar spine. The procedures aim at intervertebral immobilization or reinforcement of a posterior lumbar interbody fusion. Twenty-one patients with over 2 years of follow up were evaluated. The clinical results showed these procedures to be advantageous compared with various pedicle screw systems. We conclude that these combined procedures may be applicable to patients with various types of unstable lumbar spine problems who, until now, were treated with instrumentation surgery. The best indications for these two procedures are degenerative spondylolisthesis or degenerative disk lesion with various instabilities, degenerative canal stenosis for which wide laminectomy is essential, and herniated disk with instability during flexion.

Adult↗
PubMed1997

[Lectin-histochemical analysis of pleomorphic adenoma of the lacrimal gland].

The sugar structures of the glycoconjugates in pleomorphic adenoma of the lacrimal gland were analyzed by examining the binding sites of 5 biotinylated lectins on tissue sections with or without sialidase digestion. Both galactose (Gal) beta 1,3 N-acetylgalactosamine and Gal beta 1,4 N-acetylglucosamine were present on the surfaces of ductal basal cells and stromal cells. The galactsyl residues in the glycoconjugates of ductal basal cells were either sialylated or exposed, whereas those of stromal cells were all sialylated. Since the synthesis of sugar chains of glycoconjugates is terminated by sialylation, their structure may mature as they progress from ductal basal cells to stromal cells.

Acetylgalactosamine↗
PubMed1996

Cyclic GMP elevation by 5-hydroxytryptamine is due to nitric oxide derived from endogenous nitrosothiol in NG108-15 cells.

To clarify the involvement of nitric oxide (NO) derived from nitrosothiols (RSNO) in 5-hydroxytryptamine (5-HT)-induced Ca(2+)-independent cGMP formation (CIGF) in NG108-15 cells, we investigated the effects of 5-HT on intracellular contents of RSNO as well as of NO metabolites. 5-HT stimulation resulted in an increase in the intracellular contents of nitrate and cGMP. RSNO was detected in NG108-15 cells and was decreased by 5-HT stimulation. Furthermore, the time course of nitrate increase was coincident with that of RSNO decrease. CarboxyPTIO inhibited 5-HT-induced CIGF, whereas oxyhemoglobin failed to inhibit it. The data suggest that NO is stored in a stable form as RSNO and that 5-HT stimulates NO generation from endogenous RSNO, which is followed by elevation of cGMP via activation of cytosolic guanylyl cyclase by NO in NG108-15 cells. We suggest the existence of a novel 5-HT signal transduction pathway involved in NO generation in NG108-15 cells.

Animals↗
PubMed1996

Kyotorphin (L-tyrosyl-L-arginine) as a possible substrate for inducible nitric oxide synthase in rat glial cells.

L-Arginine (L-Arg) is an endogenous substrate for nitric oxide synthase (NOS). In the present study, we examined whether L-tyrosyl-L-Arg (kyotorphin), an endogenous analgesic neuropeptide, might be a substrate for inducible NOS (iNOS) in the brain. Both kyotorphin and L-Arg caused an accumulation of nitrites in lipopolysaccharide (LPS)-treated glial cells cultured from infant rat brains. However, such accumulation of nitrites was not induced by NG-nitro-L-Arg (a NOS inhibitor), L-tyrosyl-D-Arg (D-kyotorphin) or D-Arg. L-Leucyl-L-Arg (an antagonist for kyotorphin receptors) or bestatin (an inhibitor for kyotorphin-hydrolyzing peptidase) did not inhibit the kyotorphin-induced accumulation of nitrites in LPS-treated cells. On the contrary, L-Leucyl-L-Arg caused an accumulation of nitrites in a concentration-dependent manner. The results indicate that nitric oxide (NO) is produced in LPS-treated glial cells directly from kyotorphin through the catalytic action of iNOS.

Analgesics↗
PubMed1996

Senescence-accelerated mouse. Neurochemical studies on aging.

Senescence-accelerated mouse (SAMP8) is known as a murine model of accelerated aging and memory dysfunction. The binding activity of [3H] 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide (PK-11195) as a neurochemical marker of gliosis markedly increased with aging in the cerebral cortex and hippocampus of SAMP8. Immunoreactivity for glial fibrillary acidic protein (GFAP) was also enhanced. A beta-amyloid precursor protein (APP)-like immunoreactivity and 27-kDa-carboxyl terminal fragments of APP increased in SAMP8 brain. In addition, anti-APP antibody stained reactive astrocytes surrounding spongy degeneration in brain stern of SAMP8. These results suggest that astrocytosis and production of APP-derived fragments occur markedly in SAMP8 brains.

Aging↗
PubMed1996

Inhibition by CTLA4Ig of experimental allergic encephalomyelitis.

B7-1 and B7-2 are well characterized costimulatory ligands on Ag presentation cells for the CD28 and CTLA4 receptors on T cells. The fusion protein CTLA4Ig can block this interaction and prevent specific T cell activation. The development of fatal CD4+ T cell-mediated experimental allergic encephalomyelitis (EAE) in susceptible female Lewis rats was optimized by immunization with 20 mg of guinea pig spinal cord homogenate in CFA on day 0 with three doses of 1 microgram pertussis toxin given i.v. on days 0, 3, and 7. This immunization regimen uniformly resulted in the development of severe clinical neurologic signs of EAE with 100% mortality by day 17 postimmunization. Treatment with 0.5 mg/dose of rhCTLA4-Ig on days - 2, 0, 3, 6, 9, 12, 15 and 18 significantly decreased the incidence, delayed the onset, and reduced the severity of clinical EAE (p = 0.0002 vs control by the Mann-Whitney U test) enough to completely prevent fatal EAE, whereas treatment with control human IgG had no effect. Histologically, perivascular neutrophilic infiltrates were also dramatically decreased in the spinal cords of animals treated with CTLA4 but not in those treated with control human IgG. The proliferative response to encephalitogenic Ags (guinea pig myelin basic protein and proteolipid protein) by lymph node cells from animals immunized with guinea pig spinal cord 10 days before was also significantly suppressed in vitro by CTLA4Ig (1 microg/ml). However, the protective effect of CTLA4Ig could be completely prevented by the daily i.p. administration, from day 0 to 10, of exogenous human rIL-2 (180,000 IU). These results indicate a critical requirement of the costimulatory B7/CD28 pathway early in the development of CD4+ T cell-mediated EAE in the rat.

Abatacept↗