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Biomedical subjects

N Imai

Publications and source records attributed to N Imai.

At least 19 recordsLinked to original sources
PubMed1999

Chamber-specific regulation of heme oxygenase-1 (heat shock protein 32) in right-sided congestive heart failure.

Heme oxygenase (HO)-1 is a stress protein (HSP 32) and, together with HO-2, catalyses oxidation of the heme molecule to generate carbon monoxide, a gas with vasodilatory properties, and bilirubin, an antioxidant. Right-sided heart failure (RHF) resulted in a two-fold increase in the HO-1 transcript (;1.8 kb) in the right ventricle (RV) of RHF dogs compared to that of controls. In contrast, the left ventricle showed no increase in HO-1 mRNA in RHF. The change in HO was unique to HO-1, because neither the HO-2 transcripts (;1.3 and 1.9 kb) nor the HSP 70 mRNA was altered in either ventricle. This increase in HO-1 mRNA in RV was accompanied by a two-fold increase in immunoreactive HO-1 protein, as judged by Western blot analysis, as well as by a significant increase in cGMP levels. There was, however, no significant increase in RV total nitric oxide synthase activity in RHF. Furthermore, since norepinephrine infusion also increased HO-1 transcript and protein levels, the HO-1 system probably was induced in RHF by the increased interstitial norepinephrine levels known to occur in failing myocardium. This differential regulation and induction of HO-1 gene in the failing ventricle might be one of the defense mechanisms by which the heart attempts to protect from stress caused by congestive heart failure.

Animals↗
PubMed1999

Molecular cloning of mouse p47, a second group mammalian RuvB DNA helicase-like protein: homology with those from human and Saccharomyces cerevisiae.

A 47k protein (p47) in a high-salt buffer extract of a rat liver nuclear matrix fraction was purified by means of a wheat germ agglutinin affinity column, reversed phase HPLC, and SDS-PAGE, and partial amino acid sequences were analyzed. Based on these sequences, the mouse cDNA of the protein was cloned and sequenced, and its amino acid sequence was deduced. Mouse p47 consists of 463 amino acid residues with a molecular weight of 51,112. The amino acid sequences of human and Saccharomyces cerevisiae p47s were also deduced from the nucleotide sequences of "expressed sequence tag" fragments and genomic DNA, respectively. These sequences contain helicase motifs and show homology to bacterial RuvB DNA helicases acting in homologous recombination. They also show homology with the putative mammalian helicases p50/TIP49 and RUVBL1. Comparison of the amino acid sequences of p47 group proteins and those of p50/TIP49 group proteins revealed the p47 group proteins to comprise a group distinct from the p50/TIP49 proteins. Ultracentrifugation and gel filtration analyses showed that p47 in the rat liver cytosol fraction exists as large complexes of 697k.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1999

The leukotriene B4 receptor antagonist ONO-4057 inhibits nephrotoxic serum nephritis in WKY rats.

To evaluate the role of leukotriene B4 (LTB4) in glomerulonephritis, this study was conducted to examine whether ONO-4057, an LTB4 receptor antagonist, moderated nephritis caused by the injection of nephrotoxic serum (NTS) into Wistar-Kyoto rats. Rats were given intraperitoneal injections of ONO-4057 or phosphate-buffered saline 24 h before the injection of NTS. These rats subsequently received equal doses of ONO-4057 or phosphate-buffered saline 3 h and 1, 2, 3, 4, 5, and 6 d later. Compared with the control groups, ONO-4057 treatment significantly reduced proteinuria and hematuria, suppressed the glomerular accumulation of monocytes/macrophages, and reduced the formation of crescentic glomeruli in a dose-dependent manner. These results suggest that LTB4 is responsible for the crescentic formations and renal dysfunction associated with NTS nephritis. The LTB4 receptor antagonist ONO-4057 may thus be beneficial in the treatment of crescentic glomerulonephritis.

Animals↗
PubMed1999

[Effect on gene expression of the expanded CTG repeat on 3'-untranslated region of myotonic dystrophy (DM) protein kinase].

Myotonic dystrophy is an autosomal dominant heritable disease associated with an expansion of CTG trinucleotide repeat within 3' untranslated region of the DMPK gene. The key question is how the mutation in the 3' untranslated region of the DMPK gene exerts an dominant effect at the cellular level, despite the fact that it does not alter the protein coding region of the gene. Although the mechanism of myotonic dystrophy remains controversial, some evidence suggests that CUG repeats in the DMPK mRNA may have pathological effects. A hypothesis on molecular mechanism of DM pathogenesis, in terms of RNA-protein interactions and regulation of gene expression through the 3' untranslated region of mRNAs, was discussed.

Gene Expression Regulation, Enzymologic↗
PubMed1998

Comparison of complications of vaginal hysterectomy in patients with leiomyomas and in patients with adenomyosis.

We reviewed 1246 vaginal hysterectomies performed at Handa City Hospital between January 1984 and December 1996. We divided the patients into 2 groups: those with leiomyomas (n = 893) and those with adenomyosis (n = 353). There was no difference in operative time and estimated blood loss between the 2 groups when analyzed by uterine weight. However, adenomyosis was associated with an increased risk of bladder injury.

Adult↗
PubMed1998

Magnetic resonance imaging with gadolinium-diethylenetriamine pentaacetic acid is useful in assessment of tubal patency in a patient with iodine-induced hypothyroidism.

A 32-year-old woman presented for evaluation of primary infertility. Because she had a history of iodine-induced hypothyroidism, conventional hysterosalpingography was contraindicated. Tubal patency was assessed by magnetic resonance imaging (MRI) after infusion of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). Visualization of the contrast medium in the peritoneal cavity revealed tubal patency. Our case indicates that MRI with gadolinium-diethylenetriamine pentaacetic acid is a safe, simple, and easy way to confirm that at least one tube is patent when a patient is at risk for hysterosalpingography. To our knowledge, this is the first report that tubal patency was diagnosed on MRI.

Adult↗
PubMed1998

Effects of a novel elastase inhibitor, ONO-5046, on nephrotoxic serum nephritis in rats.

ONO-5046 is a potent, specific and intravenously active inhibitor of neutrophil elastase. To examine the role of elastase in glomerulonephritis, we tested the effects of ONO-5046 on nephrotoxic serum (NTS) nephritis in a rat model of the disease in humans. Rats were administered ONO-5046 or phosphate-buffered saline (PBS) intraperitoneally 24 hours prior to injection of NTS, and they were then given equal doses of ONO-5046 or PBS three hours and 1, 2, 3, 4, 5 and 6 days later. Compared with the control groups, ONO-5046 significantly reduced proteinuria and hematuria, and suppressed the formation of crescentic glomeruli in a dose-dependent manner. Our results suggest that neutrophil elastase participates in NTS nephritis by degrading glomerular basement membrane proteins, and that the elastase inhibitor, ONO-5046, suppresses crescentic formation and glomerular injury caused by elastase.

Animals↗
PubMed1998

Influence of intermittent ischemia on thioacetamide-induced rat liver cirrhosis.

We studied the influence of intermittent ischemic injury on thioacetamide-induced liver cirrhosis in rats. Wistar rats were divided into group A, intermittent ischemic injury to liver cirrhosis, and group B, continuous ischemic injury to liver cirrhosis. Total ischemic time was 60 min in both groups. In group A, ischemic injury consisted of a repetition 4 times of 15 min ischemia and 5 min reperfusion. The ATP level of the liver was measured before ischemia, before reperfusion, and 60 min after reperfusion. Bile was collected to determine bile flow rate. The ATP level in the liver tissue 60 min after reperfusion was significantly (p < 0.05) higher in group A than in group B. The ATP level immediately before reperfusion was also significantly (p < 0.05) higher in group A than in group B. The survival rate 1 week after ischemic injury and bile flow rate 60 min after reperfusion were significantly (p < 0.01) higher in group A compared with those in group B. The energy level was much higher in intermittent ischemic injury than in continuous ischemic injury immediately before reperfusion and after reperfusion. Survival rate and bile flow rate were higher in intermittent ischemic injury than in continuous ischemic injury. Therefore it suggests that the viability of the liver was maintained better in intermittent ischemic injury than in continuous ischemic injury.

Adenosine Triphosphate↗
PubMed1998

Gonadotropin-releasing hormone-induced elevation of serum hCG in choriocarcinoma: a case report.

We evaluated the effect of GnRH on the serum hCG level in gestational trophoblastic disease (GTD). Five patients with GTD were studied. Three patients had hydatidiform mole (two complete and one partial mole) and two had choriocarcinoma. Blood samples were collected immediately before and 30, 60 min after the 100 microg GnRH iv injection, followed by hCG assay. Only one case of choriocarcinoma demonstrated an hCG increase after intravenous administration of GnRH (positive GnRH test). In that case, the hCG level dropped to the normal range after eight cycles of chemotherapy but the GnRH test was still positive, suggesting the existence of viable cancer cells. Since the GnRH test became negative, no increase in hCG has been observed, indicating that the patient achieved complete remission. Although a positive GnRH test is not common in GTD, GnRH test before treatment might be useful to find a positive case where the test can be repeated to determine complete remission and the time when the chemotherapy may be discontinued.

Adult↗
PubMed1998

Resonance imaging of the eustachian tube cartilage in microtia.

OBJECTIVE: The purpose of this study was to determine whether external and internal defects in microtia are related. METHOD: Magnetic resonance images of the eustachian tube cartilage were evaluated for 20 patients who had unilateral microtia. Nineteen patients were classified as Grade 2, and one was classified as Grade 3. The Grade 3 patient also had unilateral facial palsy. RESULTS: On T1-, T2-, and proton-density-weighted images, the eustachian tube cartilage was clearly identified as a pair of straight lines with low signal intensity. There was no evidence of hypoplasia of the eustachian tube cartilage on the microtic side in any Grade 2 patient, but hypoplasia was evident on the microtic side of the patient classified as Grade 3. CONCLUSION: These findings are consistent with the view that impairment of embryonic development before 6 weeks results in injury to the immature primordium and malformation of both the external and middle ear. In contrast, injuries that occur at a later fetal age (i.e., after 3 months) do not appear to cause middle ear malformations.

Adolescent↗
PubMed1997

Missense mutations of the glycoprotein (GP) Ib beta gene impairing the GPIb alpha/beta disulfide linkage in a family with giant platelet disorder.

We describe here the molecular basis of an isolated hereditary giant platelet disorder (GPD) which is not accompanied with thrombocytopenia or leukocyte inclusion. Platelet aggregation with ristocetin and botrocetin was almost normal in this patient. Flow cytometric analysis showed that the glycoprotein (GP) Ib/IX complex was expressed on the platelet membranes at decreased levels. The amount of platelet GPIb alpha and the plasma glycocalicin concentration, the water-soluble extracellular portion of GPIb alpha, were also decreased. The anti-GPIb alpha antibody coprecipitated GPIb beta and GPIX, although the ratios of these polypeptides to GPIb alpha was greatly decreased compared with the ratio in normal platelets. Immunoblot analysis under nonreduced conditions showed that most of the GPIb alpha in the patient's platelets was not disulfide linked with GPIb beta. DNA sequencing analysis showed compound heterozygosity for two independent single nucleotide substitutions: from Tyr (TAC) to Cys (TGC) at residue 88, and from Ala (GCC) to Pro (CCC) at residue 108 in her GPIb beta gene. These substitutions were not found in genomic DNA samples from 108 normal individuals. These mutations might result in decreased expression of the GPIb/IX complex and may influence the association of the complex with the membrane skeleton, consequently impairing normal platelet morphology. Furthermore, the phenotype caused by mutations in the subunits of the GPIb/IX complex could span the spectrum from a normal phenotype, to isolated GPD, to a full-blown bleeding disorder, such as Bernard-Soulier syndrome.

Adult↗
PubMed1997

Establishment and characterization of a new erythropoietin-dependent acute myeloid leukemia cell line, AS-E2.

We have established an erythropoietin-dependent human leukemia cell line, AS-E2, from a patient with acute myeloid leukemia. These cells have many characteristics of late erythroid progenitor cells, they are positive for CD36, Glycophorin A, and CD71 but negative for CD41, and positive for benzidine and PAS staining. These cells express GATA-1 and have low affinity erythropoietin (EPO) receptor on their surface. Interestingly, AS-E2 cells are strictly dependent on EPO for their growth and survival; other cytokines including GM-CSF, stem cell factor, or IL-3 cannot support the growth of this cell line. These features are similar to late erythroid lineage cells, like normal BFU-E or CFU-E, and we have demonstrated that EPO stimulation induces the tyrosine phosphorylation of several proteins in AS-E2 cells including the EPO receptor and JAK2 kinase. This new cell line is a useful reagent to study biological and molecular events during the late stages of erythropoiesis, and to understand transforming events in human erythroid cells.

Acute Disease↗
PubMed1997

Characterization of the binding of nuclear envelope precursor vesicles and chromatin, and purification of the vesicles.

The binding of nuclear envelope precursor vesicles and chromatin was characterized by using an in vitro system constituted from a Xenopus egg extract and demembranated Xenopus sperm chromatin. The results of binding studies in the presence of salts, urea, and a chelator showed that the binding involves an ionic interaction. Chemical modification studies suggested that a protein(s) in the vesicles, which is responsible for the binding with chromatin, has essential lysine, histidine, and methionine residues. The vesicle protein could not be extracted from vesicles with 1 M KCl, 2 M urea, or 0.1 M Na2CO3, suggesting that it is an intrinsic membrane protein. The protein was denatured with 8 M urea and 0.1 M Na2CO3, and could be renatured by incubation at 23 degrees C, suggesting that the native conformation of the protein is important for the binding. Affinity purification of nuclear envelope precursor vesicles was achieved by binding to chromatin and dissociation with 0.24 M NaCl. The vesicle fraction thus obtained exhibited the ability to form nuclear envelope on incubation with chromatin in Xenopus egg cytosol without any other membrane fraction. These results suggested that there is a nuclear envelope precursor vesicle population containing both a chromatin targeting protein and vesicle fusion machinery.

Animals↗
PubMed1997

In vivo effect of recombinant human leukemia inhibitory factor in primates.

Leukemia inhibitory factor (LIF) is known to be a causative factor for cachexia and thrombocytosis in nude mice bearing human cancer cells. In the present study, we investigated whether recombinant human (rh) LIF can induce these biological activities in a primate model. rhLIF was synthesized by the expression of LIF protein in Escherichia coli. rhLIF (5, 20, or 80 micrograms/kg) was administered subcutaneously twice daily to cynomolgus monkeys for 14 consecutive days. A remarkable decrease of body weight (10%) was observed in the 80 micrograms/kg/day group. Approximately two-fold increases in platelet counts were observed at doses higher than 5 micrograms/kg/day when compared with control counts. These biological effects disappeared soon after the cessation of rhLIF treatment. Macroscopically, a remarkable reduction in subcutaneous fatty tissues and severe splenomegaly were observed. The results of this study demonstrate that rhLIF induces weight loss and thrombocytosis in a primate model.

Alanine Transaminase↗