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N Inoue

Publications and source records attributed to N Inoue.

At least 325 records · Page 18Linked to original sources
PubMed1995

Experimental study on the optimum flow rate and pressure for selective cerebral perfusion.

The optimum flow rate and pressure for selective cerebral perfusion during moderate hypothermia (25 degrees C) were investigated in 36 mongrel dogs. Cerebral perfusion was performed for 90 minutes at a flow rate of 100% (the physiologic flow rate), 50%, 25%, and 0%, or no flow (cerebrocirculatory arrest). Somatosensory evoked potentials were monitored to assess brain function. An excess lactate level was considered an index of anaerobic cerebral metabolism, and histopathologic evaluation was performed. Somatosensory evoked potentials showed no abnormalities at flow rates of 100% and 50%, but became abnormal in some dogs at 25% and in all dogs under no-flow conditions. The excess lactate level only increased at a no-flow rate, but not significantly. Histopathologic evaluation showed no ischemic changes at flow rates of 100% and 50%, but there were slight ischemic changes at 25% and severe ischemic damage at no flow. The mean carotid arterial pressure was 63.1 +/- 5.9, 39.8 +/- 6.2, 24.9 +/- 6.0, and 11.3 +/- 3.5 mm Hg at a flow rate of 100%, 50%, 25%, and no flow, respectively. These results suggest that the safe range of flow rates for cerebral perfusion during moderate hypothermia is more than 50% of the physiologic level with a carotid arterial pressure of about 30 mm Hg or more.

Animals↗
PubMed1995

The production of recombinant human erythropoietin.

Erythropoietin (EPO) is the glycoprotein hormone that promotes differentiation of erythroid progenitor cells in bone marrow. The normal kidney produces EPO to maintain erythrocyte for oxygen supply. This hormone activity was found in the serum of anemic animals in the 1890s. Renal failure results in severe anemia because of reduced EPO production, therefore anemia patients expected EPO treatment for long time. However, this was difficult due to the limited amount of EPO. Many researchers have tried to isolate EPO since the 1950s. Finally Miyake and Goldwasser purified highly active EPO from the urine of aplastic anemia patients. Since then, the characteristics and structural information from the purified material accelerated the cloning of the EPO gene. Mammalian cells were essential to produce EPO, because EPO contains 40% carbohydrate that plays some important roles in its activity, stability and biosynthesis. In 1984, two groups succeeded in cloning the EPO gene and expressing this gene in mammalian cells. Recombinant human EPO is currently available for anemia treatment. In this paper, we review production in mammalian cells, molecular characterization, especially carbohydrate moieties, and clinical applications of recombinant EPO.

Amino Acid Sequence↗
PubMed1995

Principle of the bark of Phellodendron amurense to suppress the cellular immune response: effect of phellodendrine on cellular and humoral immune responses.

Previously we have isolated the quaternary base alkaloids, magnoflorine and phellodendrine, from Phellodendri Cortex (cortex of Phellodendron amurense Rupr., Rutaceae) as the biologically active principles to suppress local graft-versus-host (GvH) reactions in mice. In this paper, we focus on phellodendrine. Phellodendrine suppressed local semisyngeneic GvH reactions and systemic allogeneic GvH reactions in X-ray irradiated recipient mice. Phellodendrine also suppressed the induction phase of sheep red blood cell (SRBC)-induced delayed type hypersensitivity in mice and tuberculin-induced delayed type hypersensitivity in guinea pigs, but did not suppress the effector phase of these reactions. Surprisingly, phellodendrine, unlike prednisolone and cyclophosphamide, did not affect antibody production in mice to SRBC. Phellodendrine was expected to be a valuable new type of immunosuppressor against the cellular immune response.

Animals↗
PubMed1995

Human herpesvirus 6B origin-binding protein: DNA-binding domain and consensus binding sequence.

We previously demonstrated by a DNA-binding assay that the human herpesvirus 6B (HHV-6B) replication origin has a structure similar to those of alphaherpesviruses, although the HHV-6B and herpes simplex virus type 1 (HSV-1) origin-binding proteins (OBPs) and origins are not interchangeable. Here we describe additional properties of the interaction between HHV-6B OBP and the HHV-6B origin. Competitive electrophoretic mobility shift assays (EMSAs) with DNA duplexes containing single-base alterations allowed deduction of a consensus DNA sequence for HHV-6B-specific OBP binding, YGWYCWCCY, where Y is T or C and W is T or A, while that for HSV-1-specific binding was reported to be YGYTCGCACT. By EMSA, the HHV-6B OBP DNA-binding domain was mapped to a segment containing amino acids 482 to 770. However, in Southwestern (protein-DNA) blotting, the region sufficient for the DNA binding encompassed only amino acids 657 to 770. Similarly, Southwestern blotting showed that amino acids 689 to 851 of HSV-1 OBP had HSV-1 origin-binding activity, although this region was insufficient for origin binding in the EMSA. Although the longer DNA-binding domains identified by EMSA have marginal overall homology among HHV-6B and alphaherpesvirus OBP homologs, the smaller regions sufficient for the binding observed by Southwestern blotting have significant similarity. From these results, we propose a hypothesis that the DNA-binding domain of herpesvirus OBPs consists of two subdomains, one containing a conserved motif that contacts DNA directly, and another, less well conserved, that may modulate either the conformation or accessibility of the binding domain.

Amino Acid Sequence↗
PubMed1995

Molecular regulation of the bovine endothelial cell nitric oxide synthase by transforming growth factor-beta 1.

The promoter region of the endothelial cell nitric oxide synthase (ecNOS) gene contains potential response elements for transforming growth factor-beta 1 (TGF beta 1). TGF beta 1 plays an important role in the pathogenesis of atherosclerosis, vascular hypertrophy, and angiogenesis. We therefore sought to determine whether TGF beta 1 might modulate ecNOS expression in bovine aortic endothelial cells (BAEC). TGF beta 1 increased ecNOS mRNA in a dose-dependent manner. TGF beta 1 also increased ecNOS protein content. The production of nitrogen oxides (NOx), assessed by chemiluminescence, and nitric oxide synthase activity, assessed by arginine/citrulline conversion were increased in TGF beta 1-treated cells. Transcriptional activity of the 5'-flanking promoter region of the ecNOS gene was increased by TGF beta 1, as assessed by transfection with promoter/luciferase constructs. Deletion analysis suggested that the TGF beta 1-response element was present between nucleotides -1269 and -935 from the first transcription start site, in which a putative nuclear factor-1 (NF-1) binding site existed. Gel shift assays showed that nuclear protein(s), immunologically similar to CCAAT transcription factor/NF-1, bound to the putative NF-1 binding site in a sequence-specific manner. Mutation of the putative NF-1 binding site in the promoter/luciferase construct significantly decreased the responsiveness to TGF beta 1. In conclusion, TGF beta 1 increases ecNOS expression associated with an increase in production of NO in BAEC. This response is probably mediated by transcriptional activation of the ecNOS gene promoter.

Amino Acid Oxidoreductases↗
PubMed1995

Inhibition of endothelial nitric oxide synthase activity by protein kinase C.

Nitric oxide (NO) is an important molecular messenger accounting for endothelium-derived relaxing factor. Recently, NO synthase (NOS) from cultured endothelial cells has been purified and molecularly cloned. To evaluate the effect of phosphorylation by protein kinase C (PKC) and cyclic AMP-dependent protein kinase (PKA) on endothelial constitutive NOS catalytic activity, we incubated purified endothelial NOS with PKC or PKA. Endothelial NOS was stoichiometrically phosphorylated by PKC and PKA. In intact bovine aortic endothelial cells (BAECs), NOS was phosphorylated by stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA). NOS activity measured by the conversion of [3H]arginine to [3H]citrulline in homogenates of BAECs treated with TPA or phorbol 12,13-dibutyrate was reduced by 30%, whereas dibutylyl cyclic AMP did not affect NOS activity. Moreover, we measured NO release from cultured BAECs by a chemiluminescence method to examine the effect of PKC and PKA on endothelial NOS activity. In cultured BAECs, ATP gamma S and A23187 induced NO release in time- and dose-dependent manners. Phorbol esters such as TPA and phorbol 12,13-dibutyrate dose dependently inhibited NO release stimulated by A23187 as well as ATP gamma S. Reduction of NO release by TPA was almost completely prevented by pretreatment with staurosporine, an inhibitor of PKC. NO release by A23187 was increased in PKC-downregulated BAECs. In contrast, dibutylyl cyclic AMP or 8-bromo cyclic GMP had no effect on NO release from BAECs induced by A23187 or ATP gamma S. These results indicate that phosphorylation of NOS by PKC is associated with a reduction of its catalytic activity in vascular endothelial cells.

Amino Acid Oxidoreductases↗
PubMed1995

Involvement of pituitary hormone in the sex-related regulation of hepatic epoxide hydrolase activity in mice.

The involvement of the pituitary gland in the expression of sex-related differences in the activities of epoxide hydrolase (EH) in liver was examined in hypophysectomized and neonatally monosodium L-glutamate (MSG)-treated male and female mice. In hypophysectomized mice, the hepatic microsomal EH activity of males and females increased considerably above those of the respective sham-operated controls, and the female activity exceeded that of the sham-operated males. The hypophysectomy caused a decrease in soluble EH activity in males, while the operation led to an elevation of the activity in females. Neonatal treatment with MSG resulted in marked increases of microsomal EH activity in males and females at adulthood and the activity was about 2 times that of the male control mice. Treatment of hypophysectomized males and females with growth hormone (GH) resulted in a significant decrease in microsomal EH activity below those of the corresponding hypophysectomized controls, while the hormone treatment had no effect on the soluble enzyme activities. These results suggest that murine hepatic microsomal EH activity is principally under the suppressive control of the pituitary and GH is a causal hormone involved in the expression of sexual dimorphism in the enzyme activity.

Animals↗
PubMed1995

No relation of plasma morphine level to the severity of naloxone-induced withdrawal in acute morphine-dependent rats.

Plasma morphine concentration and naloxone-precipitated withdrawal body weight loss and plasma corticosterone (PCS) increase were determined at 12, 18 and 24 hr after i.v. infusion of morphine at a constant rate of 10 mg/kg/hr for 4 hr in Sprague-Dawley rats. Plasma morphine concentration declined 98.0% within 12 hr and further declined 58.8% during 12-24 hr after morphine infusion. There was a significant difference between plasma morphine concentrations at 12 and 24 hr after the morphine infusion. Naloxone (0.5 and 2.0 mg/kg)-precipitated withdrawal, but not spontaneous withdrawal, was elicited at 12-24 hr after the morphine infusion, and the severity of withdrawal precipitated by 2.0 mg/kg naloxone was the same at 12-24 hr after the morphine infusion. Furthermore, there was no significant correlation between plasma morphine concentration and body weight loss or PCS increase. The results suggest that a constant degree of morphine dependence is sustained during 12-24 hr after the morphine infusion and the severity of naloxone-precipitated withdrawal is not related to the plasma morphine concentration at the time of naloxone injection, that is, the rate of morphine removal from its receptor sites.

Animals↗
PubMed1995

Acute revascularization for bihemispheric anterior cerebral artery thrombosis--case report.

A 65-year-old male presented with rapidly progressive paraparesis and akinetic mutism due to occlusion of the bihemispheric anterior cerebral artery (ACA). He was treated by intra-arterial thrombolytic therapy but reocclusion of the arteriosclerotic lesion occurred. Bilateral superficial temporal artery (STA)-ACA anastomoses achieved lasting neurological improvement. Bilateral STA-ACA anastomoses are quite effective to prevent ischemia of the bilateral ACA territories.

Aged↗
PubMed1995

Retrograde perfusion of the cerebral vein with antioxidant LY231617 reduces brain damage in the rat focal ischemia model.

Retrograde perfusion of the cerebral vein (RPCV) with antioxidant LY231617 was evaluated in the focal ischemia model in rats as a new therapeutic route to deliver cytoprotective agents more selectively and efficiently into ischemic brain tissue. Thirty-six Sprague-Dawley rats were divided into Groups A through D. Focal ischemia was induced for 3 hours in the rats, then all groups were treated differently for 2 hours and then sacrificed. Rats in Group A (n = 10) served as the control group and was left untreated. Rats in Group B (n = 10) received an intravenous infusion of LY231617 (10 mg/kg/hr). Rats in Group C (n = 6) received saline (86 microliters/min) through RPCV. Rats in Group D (n = 10) received LY231617 (10 mg/kg/hr) in saline (86 microliters/min) through RPCV. The regional cerebral blood flow (rCBF) was measured using [14C]iodoantipyrine autoradiography, and phorbol 12,13-dibutyrate (PDBu) binding by in vitro [3H]PDBu autoradiography. Ischemic brain damage was assessed quantitatively after staining with cresyl violet and Luxol fast blue. Rats in Group D showed significantly higher rCBF (41-400%, p < 0.05) in the ischemic cortical and subcortical areas, and a significant reduction (66%, p < 0.01) in the total volume of ischemic damage and reduction of PDBu binding (p < 0.05) in the lateral striatum of the ischemic hemisphere, as compared to the rats in Groups A-C. RPCV with antioxidant LY231617 achieves a more beneficial effect on focal ischemic tissue than regular systemic administration.

Animals↗
PubMed1995

Chronic toxicity of tar from heavy-duty diesel exhaust following intratracheal instillations to the lungs of hamsters.

Chronic toxicity of tar from heavy-duty diesel exhaust (HD tar) was studied in male Syrian golden hamsters which received 15 mg, 7.5 mg or 1.5 mg of HD tar as the total dosages by intratracheal instillations once a week for 15 weeks. As a control group, hamsters were treated with the 0.1 ml of Tween 60: ethanol: phosphate buffer (pH 6.88, 0.25 M) solution (5.8: 8.7: 100 by volume) once a week in the same manner. The survival rate during the instillation period in the group given 15 mg of HD tar, the high-dose group of HD tar, was the lowest, and the effect was dose-dependent. However, the survival rates during the subsequent observation period showed no marked differences among HD tar treated groups. During their total life span, one papilloma in the larynx was seen in the 44 hamsters in the group given 1.5 mg of HD tar, one papilloma in the larynx was appeared in the 59 hamsters in the group given 1.5 mg of HD tar and one lung adenoma was developed in the 58 hamsters in the control group. There were no tumors in the respiratory tract in the group given 7.5 mg of HD tar. Concerning the histopathological findings of the lung, the incidence of alveolar cell or bronchiolar cell hyperplasia in the group given 1.5 mg of HD tar was significantly higher than that in the control group. From these results, although we could not observe any tumorigenicity or carcinogenic effect of HD tar, it would seem that HD tar caused weak but positive damage to the lungs of hamsters.

Animals↗
PubMed1995

[Peripheral blood stem cell transplantation for rapidly spreading myeloma].

We report a case of rapidly spreading myeloma of immature cell morphology treated by peripheral blood stem cell transplantation (PBSCT). A 54-year-old man had a right orbital tumor, which subsequently was removed and proved to be plasmacytoma. Three years later a mass lesion appeared in his left lung and bilateral kidneys. The specimen obtained at lung biopsy confirmed the diagnosis of plasmacytoma. Serum M-protein, IgG lambda was increased, but there was no increase in plasma cells in the bone marrow. Since chemotherapy with VAD did not show any improvement, a high dose etoposide (500 mg/day, 4 days) was administered. When bone marrow suppression recovered, PBSCs were harvested (3.3 x 10(6)/kg). After conditioning therapy with cyclophosphamide (2.0 g/day, 2 days), etoposide (200 mg/day, 3 days) and ranimustine (200 mg/day, 2 days), the stored PBSCs were injected. Minor response was obtained and he was discharged. 2 months thereafter, it was found that plasma cells increased in the bone marrow. He died of pulmonary bleeding soon. Autopsy revealed immature plasma cell infiltration in multiple organs including the heart, liver, spleen, kidneys, intestine, bone and bone marrow.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Effect of branched-chain amino acids on glutamate neurotoxicity in primary cultured rat cerebral neurons].

The neurotoxicity of glutamate has recently been postulated to participate in the pathogenesis of amyotrophic lateral sclerosis (ALS), and branched-chain amino acids have been proposed as possible therapeutic compounds for this disease. This study was undertaken to investigate whether branched-chain amino acids have any protective effect on cultured neurons exposed to glutamate. Primary cultures of cerebral neurons were prepared from fetal rats, using an established technique. For the assessment of glutamate toxicity, photomicrographs were taken before and after glutamate exposure both with phase-contrast and with bright field following incubation in trypan blue, a dye normally excluded by healthy cells. The activity of lactate dehydrogenase released from damaged cells was also measured. Exposure to glutamate in various concentrations was carried out, and leucine, isoleucine and varine, each separately, were added in advance to culture dishes. Glutamate neurotoxicity was confirmed, but no protective effect of branched-chain amino acids was observed. Although possible clinical benefit of branched-chain amino acids in ALS may not be denied, they do not prevent glutamate neurotoxicity in cultured cerebral neurons.

Amino Acids, Branched-Chain↗
PubMed1995

Hemodialysis patient regarded as a primary hyperoxaluria after long-term hemodialysis and renal transplantation.

Primary hyperoxaluria (PH) is a rare inborn error of oxalate metabolism resulted in autosomal recessive genetic defects. Clinical manifestations and end stage renal failure are developed during childhood in most cases, but occasionally they begin later in life. The diagnosis of PH is quite difficult due to diminished oxalate excretion after the renal function was declined. especially after initiation of hemodialysis therapy. We report here an adult case who was introduced into hemodialysis and subsequently regarded to have primary hyperoxaluria (PH). In clinical situations, this case had some peculiar clinical signs such as histories of frequent stone formations, impressive dental manifestations and destructive erosions of bones resembling renal osteodystrophy. There might be more PH patients among hemodialysis patients. PH should be considered in hemodialysis patients whenever curious bone changes and/or dental manifestations with history of frequent urolithiasis are recognized in the earlier course of hemodialysis therapy.

Adult↗