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Biomedical subjects

M Ohno

Publications and source records attributed to M Ohno.

At least 217 records · Page 12Linked to original sources
PubMed1996

High-affinity anti-DNA antibody parallels clinical course of immunoadsorption therapy for systemic lupus erythematosus.

Anti-DNA antibody, especially high-affinity anti-DNA antibody (ADNA), is thought to have an important role in the pathogenesis of lupus nephritis. In this study, ADNA which binds to double-stranded DNA under a high concentration of sodium chloride was measured in patients who had received immunoadsorption (IA) therapy with a dextran-sulfate column. Titers of high-affinity ADNA in the cases with renal dysfunction tended to be higher than in those without renal dysfunction. The change in the titer of high-affinity ADNA paralleled the clinical course. These findings suggest that measurement of high-affinity ADNA is useful for follow-up of the clinical course of patients who have undergone IA therapy.

Adult↗
PubMed1996

Oral biological activities of spontaneous nitric oxide releasers are accounted for by their nitric oxide-releasing rates and oral absorption manners.

We examined whether p.o. biological activities of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), a spontaneous nitric oxide (NO) releaser, and the derivatives, i.e., (+/-)-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexenyl]-3 - pyridinecarboxamide (FR144420) and (+/-)-N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-6-methyl-5- nitro-3-heptenyl]-3-pyridinecarboxamide (FR146801), could be accounted for by their NO-releasing rates and p.o. absorption manners. These compounds spontaneously released NO with the rates in the rank order of FK409 > FR144420 > FR146801. Total contribution of these drugs as NO donors in vivo was almost the same from the determination of urinary nitrite/nitrate (NOx) levels after p.o. administration of the compounds at 10 mg/kg to rats. Plasma NOx level after p.o. administration of FK409 at 10 mg/kg to rats reached maximal level at 120 min, and decreased gradually. On the other hand, plasma NOx levels time-dependently increased during 360 min after p.o. administration of FR144420 and FR146801 at the same dose. FK409 and FR144420 showed hypotensive effects immediately after p.o. administration at 10 mg/kg to rats, and the maximum response of FR144420 was less and the duration of the effect was longer than those of FK409, respectively. On the other hand, FR146801, which is most stable in solution, did not show any significant hypotensive effect during 240 min after p.o. administration at the same dose. In conclusion, the response and the duration of biological activity after p.o. administration of three spontaneous NO releasers can be closely accounted for by their NO-releasing rates and p.o. absorption manners.

Absorption↗
PubMed1996

[Evaluation of chemotherapy in the treatment of advanced colorectal cancer--pilot study of 5-FU by biochemical modulation].

We undertook a randomized trial in patients with advanced colorectal cancer, comparing 5-fluorouracil and leucovorin versus combination of these agents with additional cisplatin. Between July 1991 and October 1994, 21 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either 5-FU (500-750 mg/body) and LV (30 mg/body) for 5 days, or the combination of 5-FU and LV in the same daily dose plus cisplatin (10 mg/body). The overall responses were 30% and 36.3% for the 5-FU/LV and the 5-FU/LV/CDDP treatment arms, respectively. The three-drug combination appeared superior to 5-FU/LV for response duration. A comparative analysis of the toxicities experienced by the patients in the two treatment groups showed a comparable rate, although moderate leukocytopenia was prolonged in one patient treated with 5-FU/LV for 5 days. We conclude that the 5-FU/LV/CDDP treatment arm is an effective therapy for advanced colorectal cancer, but further attempts should be made to increase response rate, prolong response duration and assure effective therapy.

Adult↗
PubMed1996

[Neonatal hypoxic/ischemic encephalopathy: neuropathology and plasticity].

To obtain some clues for early management after neonatal hypoxic/ischemic brain injury, the cascade of cellular responses to the lesions was examined. Microglia is one of the principal glial element that responds to ischemic lesions. Microglia and astroglia may play important roles in neuronal degeneration and regeneration through secretion of some substances, such as neurotrophic factors which have been known to protect and/or rescue injured neurons. Platelet-derived growth factor B chain PDGF-B chain) is one of the neurotrophic factors, and an immediate enhancement of the expression of PDGF-B chain mRNA, protein and its receptor was observed in the injured brain. This enhancement persisted longer only in the neurons in the peri-infarct. Our findings suggested the crucial role of PDGF-B chain in the impending brain injury, as a neuroprotecting factor. Clinical application of neurotrophic factors is not anecdotal.

Animals↗
PubMed1995

N-methyl-D-aspartate stimulates dopamine release through nitric oxide formation in the nucleus accumbens of rats.

Intracerebral microdialysis technique was utilized to study the effect of NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, on N-methyl-D-aspartate (NMDA)-induced dopamine overflow in the nucleus accumbens of unanesthetized, freely moving rats. Perfusion of 1 and 3 mM NMDA through the microdialysis probe dose-dependently increased the extracellular dopamine level in the nucleus accumbens. Coapplication of 0.5 mM D-(-)-2-amino-5-phosphonovaleric acid (D-AP5), a selective and competitive NMDA receptor antagonist, significantly reduced the dopamine overflow induced by 3 mM NMDA. Perfusion of 0.5 mM NG-nitro-L-arginine alone did not affect the basal dopamine level, whereas it suppressed the NMDA-evoked dopamine overflow in the nucleus accumbens when concurrently applied with 3 mM NMDA. These results suggest that NO mediates, at least in part, dopamine release resulting from NMDA receptor activation in the nucleus accumbens of rats.

Animals↗
PubMed1995

Persistent increase in dopamine release following activation of metabotropic glutamate receptors in the rat nucleus accumbens.

Intracerebral microdialysis technique was utilized to study the effect of the metabotropic glutamate receptor agonist, 1-aminocyclopentane-1,3-dicarboxylic acid (ACDP), on extracellular dopamine concentration in the nucleus accumbens of unanesthetized, freely moving rats. Perfusion of 1 mM (1S, 3R)-ACPD, a selective metabotropic glutamate receptor agonist, through the microdialysis probe caused a significant and persistent increase in extracellular dopamine level in the nucleus accumbens, which disappeared 2 h after perfusion of (1S, 3R)-ACPD was discontinued. On the other hand, a temporary increase in dopamine overflow was observed when 1 and 3 mM N-methyl-D-aspartate (NMDA), an ionotropic glutamate receptor agonist, was perfused into the nucleus accumbens. Application of 1 mM (1R, 3S)-ACPD, an inactive isomer, into the nucleus accumbens had no effect on the extracellular dopamine concentration. The metabotropic glutamate receptor antagonist, alpha-methyl-4-carboxyphenylglycine (MCPG) (5 mM) did not affect the basal dopamine level, but it attenuated the (1S, 3R)-ACPD-evoked dopamine overflow in the nucleus accumbens when applied concurrently with 1 mM (1S, 3R)-ACPD. These results suggest that a long-lasting dopamine overflow following activation of metabotropic glutamate receptors contrasts with a transient one in response to NMDA receptor activation in the nucleus accumbens.

Animals↗
PubMed1995

Determination of left ventricular chamber stiffness from the time for deceleration of early left ventricular filling.

BACKGROUND: A noninvasive measure of left ventricular (LV) chamber stiffness (KLV) would be clinically useful. Our theoretical analysis predicts that KLV can be calculated from the time for deceleration of LV early filling (tdec) by [formula: see text] where p = density of blood, L = effective mitral length, and A = mitral area. METHODS AND RESULTS: We tested this hypothesis in eight conscious dogs instrumented for measurement of LV pressure (P) with use of a micromanometer and volume (V) with use of sonomicrometers. KLV was determined as the slope of the late diastolic portion of the LV P-V loop. KLV was varied from 0.99 +/- 0.35 to 2.58 +/- 0.92 mm Hg/mL with use of three graded doses of phenylephrine. We assumed that p = 1.0 and that L/A = 3.4. Thus, we predicted that KLV = (0.08/tdec)2. The LV filling pattern was determined from the derivative of LV volume (dV/dt). tdec was measured from peak early filling to the end of early filling. Predicted KLV and actual KLV were closely correlated (r = .94, SEE = 0.06 mm Hg/mL, P < .05). The regression line was close to the line of identity (slope = 0.95, intercept = 0.13 mm Hg/mL). Dobutamine did not alter the relation between tdec and KLV.tdec determined from the mitral valve flow velocity measured with Doppler echocardiography correlated well with that measured by dV/dt (r = .89, P < .01) but was 0.02 seconds longer. KLV-calculated tdec from the corrected Doppler tdec provided a good estimate of measured KLV (r = .75, SEE = 0.5 mm Hg/mL, P < .01). CONCLUSIONS: LV chamber stiffness can be determined from the time for deceleration of LV early filling, which can be measured noninvasively.

Animals↗
PubMed1995

Identification of the factors that interact with NCBP, an 80 kDa nuclear cap binding protein.

It has been shown that the monomethylated cap structure plays important roles in pre-mRNA splicing and nuclear export of RNA. As a candidate for the factor involved in these nuclear events we have previously purified an 80 kDa nuclear cap binding protein (NCBP) from a HeLa cell nuclear extract and isolated its full-length cDNA. In this report, in order to obtain a clue to the cellular functions of NCBP, we attempted to identify a factor(s) that interacts with NCBP. Using the yeast two-hybrid system we isolated three clones from a HeLa cell cDNA library. We designated the proteins encoded by these clones NIPs (NCBP interacting proteins). NIP1 and NIP2 have an RNP consensus-type RNA binding domain, whereas NIP3 contains a unique domain of Arg-Glu or Lys-Glu dipeptide repeats. We also show that NCBP requires NIP1 for binding to the cap structure. Possible roles of NIPs in cap-dependent nuclear processes are discussed.

Amino Acid Sequence↗
PubMed1995

Isolation and sequence polymorphism of a rat retinoblastoma (RB) cDNA.

A cDNA of the rat retinoblastoma gene (RB) was prepared from total RNA of rat liver using reverse transcription-polymerase chain reaction (RT-PCR). The 4432-nt sequence isolated contained 2700-nt translated and 1732-nt 3'-untranslated regions (UTR). The isolated cDNA detected poly(A)+RNAs of 5.4 and 3.4 kb in rat liver and kidney by Northern blot hybridization. The nt sequence of the isolated cDNA had 85% homology with that of mouse and 73% with human. The 899-amino-acid (aa) sequence was 95% homologous to that of mouse and 90% to human. The aa sequences of two functional domains of oncoprotein-binding and ten putative phosphorylation sites regulating RB function were conserved in the three species. However, the 3'-UTR were less homologous among the three, and had polymorphism in three portions, even in rats. These polymorphisms were strain-specific and genetically segregated. Thus, the rat RB cDNA and its sequence information may be useful for clarifying the role of the RB protein and genetic linkage analysis in basic biomedical research using rats, especially in experimental carcinogenesis.

Amino Acid Sequence↗
PubMed1995

Intrahippocampal administration of (+)-SKF 10,047, a sigma ligand, reverses MK-801-induced impairment of working memory in rats.

In order to clarify the roles of the hippocampal sigma site and phencyclidine (PCP) binding site on the NMDA receptor/channel complex in the regulation of working memory in rats, the effects of intrahippocampal administration of ligands for both binding sites on this behavior were examined with a three-panel runway task. MK-801, a potent noncompetitive NMDA antagonist with high affinity for the PCP site, significantly increased the number of working memory errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points), when injected bilaterally at 0.1 and 0.18 microgram/side into the dorsal hippocampus. However, intrahippocampal injection of (+)-SKF 10,047, a sigma ligand, at doses up to 1.0 microgram/side had no significant effect on the number of working memory errors. The working memory impairment induced by intrahippocampal MK-801 (0.18 microgram/side) was attenuated by concurrent injection of 1.0 microgram/side (+)-SKF 10,047, but not by that of 1.0 microgram/side (-)-SKF 10,047. These results suggest that activation of hippocampal sigma and PCP binding sites exerts antagonistic effects on working memory function, possibly through modulation of NMDA receptor-mediated glutamatergic neurotransmission.

Animals↗
PubMed1995

FR144420, a novel, slow, nitric oxide-releasing agent.

We report that (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409) decomposes and releases nitric oxide (NO) spontaneously in solution. (+/-)-N-[(E)-4-Ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexen-1- yl]-3- pyridinecarboxamide (FR144420) was synthesized with the aim of discovering a compound with longer duration of effects in vivo, compared with FK409. FR144420, like FK409, released NO spontaneously in solution, but the amount of NO released from FR144420 during a 5-min incubation was half the amount from FK409. In addition, FR144420 spontaneously decomposed and generated nitrite, which is an oxidative metabolite of NO, at half the rate of FK409. In a vasorelaxant study with isolated rat aorta, FR144420 had a weaker potency than FK409 (EC50 = 54 and 8.1 nM, respectively). In in vivo studies, FR144420 decreased mean blood pressure immediately after intravenous and oral administration to conscious rats. The maximum hypotensive effects of FR144420 were less than those of FK409. However, the durations of FR144420-induced (i.v. and p.o.) hypotensive effects were longer than those of FK409-induced effects. In conclusion, FR144420 is more stable and releases NO more slowly in solution than does FK409. In in vivo experiments, FR144420 showed a longer duration of effects than FK409. FR144420 may be very useful for investigating the in vivo actions of NO.

Administration, Oral↗
PubMed1995

Nitric oxide synthase inhibitors block behavioral sensitization to methamphetamine in mice.

Repeated administration of methamphetamine (1.0 mg/kg) once daily for 7 consecutive days resulted in an augmentation of the locomotor-activating effect of methamphetamine (0.5 mg/kg) challenged 72 h after the last injection. Administration of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (10 and 30 mg/kg), before daily methamphetamine injections dose dependently prevented the development of behavioral sensitization to subsequent methamphetamine challenge. The mice given another NO synthase inhibitor, NG-nitro-L-arginine methyl ester (100 mg/kg), before daily methamphetamine injections showed significantly less locomotor activity in response to 0.5 mg/kg methamphetamine challenge than the mice given daily methamphetamine alone. Such effects were not observed when the inactive isomer, NG-nitro-D-arginine methyl ester (100 mg/kg), was administered daily prior to methamphetamine. Both NO synthase inhibitors exerted the acute effect to reduce spontaneous and methamphetamine-stimulated locomotor activity, while neither spontaneous locomotion nor hyperlocomotion in response to 1.0 mg/kg methamphetamine was altered 72 h after repeated administration of NG-nitro-L-arginine (30 mg/kg) or NG-nitro-L-arginine methyl ester (100 mg/kg) alone once daily for 7 days. On the other hand, pretreatment with the NMDA receptor antagonist, MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate), at 0.2 mg/kg also suppressed the development of sensitization to the locomotor-activating effect of methamphetamine. These findings suggest that NO formation possibly mediated by NMDA receptors is involved in mechanisms underlying the development of behavioral sensitization to methamphetamine.

Amino Acid Oxidoreductases↗
PubMed1995

Glial responses to hypoxic/ischemic encephalopathy in neonatal rat cerebrum.

This study was undertaken to examine glial responses in the immature rat brain to hypoxic/ischemic injury. The results indicate that developing microglia are the first and principle glial element that responds to hypoxic/ischemic injury during the neonatal period. The astrocyte response occurs later and macrophage infiltration may be delayed or absent.

Animals↗
PubMed1995

Structures of genes encoding TATA box-binding proteins from Trimeresurus gramineus and T. flavoviridis snakes.

A cDNA encoding the Trimeresurus gramineus (Tg; green habu snake) TATA-box-binding protein (TgTBP) was cloned and sequenced. The cDNA encodes a 33-kDa protein with an extensive sequence similarity to those derived from other organisms, except for the N-terminal domain. Genes encoding TgTBP and Trimeresurus flavoviridis (Tf; habu snake) TBP (TfTBP) were isolated using a TgTBP cDNA and their nt sequences were determined. They are the first TBP genes entirely sequenced in higher animals. Both genes span over 15 kb and are constructed from eight exons and seven introns. Comparison of the loci of introns on the aligned amino-acid sequences of TBP from six organisms (Tg, Tf, mouse, Arabidopsis thaliana, Schizosaccharomyces pombe and Acanthamoeba castellanii) indicated that there are three highly conserved loci in the C-terminal domain.

Amino Acid Sequence↗
PubMed1995

Molecular evolution of group II phospholipases A2.

The nucleotide sequences of 13 cDNAs encoding group II phospholipases A2 (PLA2s), which are from viperidae snake venoms and from mammalian sources, were aligned and analyzed by phylogenetic trees constructed using various components of the sequences. The evolutionary trees derived from the combined sequences of the untranslated (5' and 3') region and the signal peptide region of cDNAs were in accord with the consequences from taxonomy. In contrast, the evolutionary trees from the mature protein-coding region sequences of cDNAs and from the amino acid sequences showed random patterns. These observations indicated that the mature protein-coding region has evolved through a process differently from the untranslated and signal peptide regions. The trees built from the nucleotide differences at each of three positions of codons in the mature protein-coding region suggested that snake-venom-gland PLA2 genes have evolved via a process different from mammalian PLA2 genes. The occurrence of accelerated evolution has been recently discovered in Trimeresurus flavoviridis venom-gland group II PLA2 isozyme genes (Nakashima et al. 1993, Proc Natl Acad Sci USA 90:5964-5968), so the present phylogenetic analysis together with the estimation of nucleotide divergence of cDNAs provides further evidence that snake-venom-group II PLA2 isozyme genes have evolved by accelerated evolution to gain diverse physiological activities.

Amino Acid Sequence↗