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Biomedical subjects

M Narita

Publications and source records attributed to M Narita.

At least 19 recordsLinked to original sources
PubMed1995

Two receptor systems are involved in the plasma clearance of tissue factor pathway inhibitor in vivo.

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of the blood coagulation factor VIIa-tissue factor complex, as well as a direct inhibitor of factor Xa. Intravenously administered TFPI is rapidly cleared from circulation predominantly via liver. We previously reported that the low density lipoprotein receptor-related protein (LRP), a multifunctional endocytic receptor, mediates the uptake and degradation of TFPI in hepatoma cells. This process is inhibited by a 39-kDa receptor-associated protein which binds to LRP and regulates its ligand binding activity. However, a distinct, low affinity binding site (perhaps heparin sulfate proteoglycans, HSPGs) on the endothelium and liver is thought to be responsible for the majority of TFPI cell surface binding. In the current study, we investigated the role of LRP and this second binding site in the clearance of 125I-TFPI in vivo using competitors and inhibitors of the receptors. Mice overexpressing the 39-kDa protein via adenoviral-mediated gene transfer displayed diminished plasma clearance of 125I-TFPI. Blockade of cell surface HSPGs sites by incubation with the positively charged molecule, protamine, inhibited 125I-TFPI binding to the hepatoma cells in vitro. In addition, preadministration of protamine in vivo prolonged the plasma clearance of 125I-TFPI in a dose-dependent manner. However, a dramatic increase of the plasma half-life of 125I-TFPI and virtual elimination of 125I-TFPI clearance was observed in mice overexpressing the 39-kDa protein and administered protamine. Taken together, our results suggest that two receptor mechanisms are involved in the clearance of TFPI in vivo.

Animals↗
PubMed1995

Inhibition of protein kinase C, but not of protein kinase A, blocks the development of acute antinociceptive tolerance to an intrathecally administered mu-opioid receptor agonist in the mouse.

A specific protein kinase C inhibitor, calphostin C, which injected alone had no effect on the antinociception induced by intrathecal (i.t.) administration of a selective mu-opioid receptor agonist, [D-Ala2,NMePhe4,Gly(ol)5]enkephalin (DAMGO), dose-dependently attenuated the development of acute tolerance to the i.t. DAMGO-induced antinociception in male ICR mice. On the other hand, a selective protein kinase A inhibitor, KT5720, did not have any effect on the development of acute tolerance to DAMGO antinociception. These findings suggest that protein kinase C, but not protein kinase A, plays an important role in the development of acute tolerance to the mu-opioid receptor agonist-induced antinociception.

Analgesics↗
PubMed1995

Pulmonary aspergillosis and pseudosequestration of the lung in chronic granulomatous disease.

We present a case of chronic granulomatous disease with an angiographically proven pseudosequestration of the lung. The patient was a 15-year-old boy who was admitted to the hospital with symptoms of fever, cough, hemoptysis and a subcutaneous abscess. Aspergillus fumigatus was isolated from the sputum and the abscess. During treatment, angiography demonstrated on anomalous blood supply to the right middle lobe. The therapeutic implications of pseudosequestration of the lung for the treatment of chronic granulomatous disease are discussed.

Adolescent↗
PubMed1995

Distribution of nitric oxide synthase in the central nervous system of Macaca fuscata: subcortical regions.

The distribution of nitric oxide synthase-immunoreactive neurons was studied in the Macaca fuscata by immunohistochemistry using antiserum against nitric oxide synthase. In the macaque lower brainstem, many nitric oxide synthase-containing cell bodies were found in the gigantocellular and parvocellular reticular nuclei, the nucleus of the spinal tract of trigeminal nerve, the cochlear nucleus, the prepositus hypoglossi and the nucleus of the solitary tract. Many nitric oxide synthase-immunoreactive perikarya were observed in the laterodorsal-pedunculopontine tegmental nucleus complex of the macaque pontine and midbrain tegmentum. In addition, there were many highly immunoreactive cell bodies in the superficial layers of the inferior and superior colliculi. In the forebrain, numerous cell bodies were observed in the caudate nucleus, putamen, nucleus accumbens, nucleus of the diagonal band, anterior perforated substance and amygdaloid complex. Whereas most of these neurons were labeled highly intense for nitric oxide synthase, there were also many lightly labeled nitric oxide synthase-immunoreactive neurons in the substantia innominata, globus pallidus, ansa peduncularis and lateral hypothalamic nucleus. The present observation indicated some species difference in the distribution of central nitric oxide synthase-containing neurons. Furthermore, the present neuroanatomical evidence that nitric oxide synthase is distributed in a variety of specific neuronal systems, with some differences in the patterns of cytoplasmic localization, further indicates the neural messenger role of nitric oxide in the central nervous system.

Amino Acid Oxidoreductases↗
PubMed1995

Inhibition of UDP-glucuronosyltransferase by aglycons of natural glucuronides in kampo medicines using SN-38 as a substrate.

7-Ethyl-10-[4-(piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), a potent anticancer agent for lung and gynecological cancers, is metabolized in vivo to the active compound, 7-ethyl-10-hydroxycamptothecin (SN-38), which is subsequently conjugated to SN-38-glucuronide by UDP-glucuronosyltransferase (UDP-GT). Three purified aglycons of natural glucuronides, baicalein, luteolin and glycyrrhetic acid, inhibited UDP-GT activity towards SN-38 as a substrate. The inhibitory potencies of these aglycons toward UDP-GT were similar to that of 1-naphthol. Based on these results, together with our previous finding that the corresponding glucuronides used in the present study strongly inhibited beta-glucuronidase in gut flora, we propose that materials in Kampo (Japanese herbal) medicines containing these aglycons of natural glucuronides could be used in vivo to decrease the enterohepatic circulation of SN-38 and other drugs.

Animals↗
PubMed1995

Measles encephalomyelitis in a patient with a history of vaccination.

Secondary vaccine failure (SVF) of measles is generally believed to run a milder course of illness than an ordinary course of infection. Severe complications such as central nervous system involvement have rarely been reported. A 12 year old girl, who had received a live attenuated measles vaccine 10 years earlier, developed an encephalomyelitis in the absence of symptoms indicative of ordinary measles such as Koplik spots. Anti-measles hemagglutination inhibition (HI) titer and measles IgM and IgG antibody titers were measured in a commercial laboratory. Measles virus genomic sequence was detected by polymerase chain reaction. Both serum and cerebrospinal fluid (CSF) samples obtained at acute phase already showed extremely high titers of HI (x8192 in serum and x1024 in CSF, respectively) and IgG antibody along with the presence of IgM antibody. Polymerase chain reaction detected the measles virus genomic sequence in the acute phase CSF. The patient's definite history of measles vaccination, high titers of HI and IgG antibodies observed at the very early stage of illness and the clinical course indicated that this patient has an encephalomyelitis due to SVF of measles. It is suggested that measles virus can be a pathogen of encephalitis without symptoms indicative of ordinary measles in individuals who received live attenuated measles vaccines.

Child↗
PubMed1995

Interleukin-6 in cerebrospinal fluid of patients with central nervous system infections.

Interleukin(IL)-6 levels were measured in cerebrospinal fluid (CSF) and serum samples from pediatric patients with central nervous system (CNS) infections by means of an enzyme-linked immunosorbent assay. Mean IL-6 concentrations in CSF samples from patients with bacterial meningitis (49,017 +/- 44,730 pg/ml) were significantly higher than those in patients with aseptic meningitis (1076 +/- 1572 pg/ml) or encephalitis (409 +/- 835 pg/ml). In aseptic meningitis and encephalitis, IL-6 levels in serum were within the lower ranges (< 100 pg/ml), in contrast with the highly elevated levels found in bacterial meningitis (14,332 +/- 18,385 pg/ml). In 5 of the 15 patients with encephalitis, elevated levels of IL-6 were observed in the initial CSF samples despite normal findings of routine CSF examinations. Also, sequential CSF samples revealed that there was an increase in the CSF cell count in two of the five patients. These results validated the potential of measuring IL-6 in CSF samples for the purpose of providing additional information on routine laboratory test results.

Blood-Brain Barrier↗
PubMed1995

Two receptor systems are involved in the plasma clearance of tissue-type plasminogen activator (t-PA) in vivo.

Tissue-type plasminogen activator (t-PA) is a serine protease, catalyzing the initial step in the fibrinolytic process. Intravenously administered t-PA is rapidly cleared from the circulation by the liver. Two distinct clearance mechanisms, which are mediated by the low density lipoprotein receptor-related protein (LRP) on liver parenchymal cells and by the mannose receptor on liver endothelial cells, have been described. Using competitors and inhibitors of the receptors, we investigated the role of LRP and carbohydrate receptors in t-PA clearance in vivo. To inhibit LRP, the 39-kD protein, which is a potent inhibitor of LRP activity, was overexpressed in the liver of mice using an adenoviral gene transfer technique. Expression of the 39-kD protein resulted in a sustained plasma concentration and an increase in the plasma half-life of 125I-t-PA from less than 1 min to 4-5 min. Blockade of the mannose receptor by intravenous administration of ovalbumin also prolonged the plasma half-life of 125I-t-PA to 3-4 min. The same degree of inhibition of t-PA clearance was also observed after administration of an inhibitor of the fucose receptor, fucosyl-BSA. However, under the conditions established for the complete blockade of the mannose receptor, no additional inhibition of t-PA clearance was observed using fucosyl-BSA, suggesting little or no role for the fucose receptor in the clearance of t-PA. Furthermore, a dramatic increase of the plasma half-life of 125I-t-PA (>> 20 min) was observed in mice overexpressing 39-kD protein and administered ovalbumin +/- fucosyl-BSA. Our results clearly demonstrate that two independent receptor systems, LRP and the mannose receptor, are involved in the hepatic clearance of t-PA.

Adenoviridae↗
PubMed1995

Desensitization of capsaicin-sensitive sensory neurons in rat stomachs on chronic treatment with sodium taurocholate.

We examined the effects of chronic treatment with 10 mM sodium taurocholate (TC) on gastric functions, capsaicin-sensitive afferent neurons and the gastric mucosa in male rats. Stomachs were mounted in Lucite chambers, and then the transmucosal potential difference (PD), luminal pH and gastric mucosal blood flow (GMBF) in response to TC or capsaicin was determined. In normal animals, 10 mM TC caused a reduction in PD, and increases in luminal pH and GMBF. Capsaicin (1 mg/ml) produced an apparent increase in GMBF without any change in PD or luminal pH. After 4- or 12-week treatment with TC, the basal PD was significantly reduced, and the luminal pH tended to increase. The increase in GMBF in response to TC or capsaicin was profoundly suppressed in TC-pretreated animals. The calcitonin gene-related peptide release in response to capsaicin was significantly reduced after 4 weeks treatment with TC. There were no microscopical changes in the oxyntic mucosa until 4 weeks after TC treatment except for exfoliation of surface cells. However, an increase in inflammatory cell infiltration was observed 12 weeks later. We conclude that chronic treatment with TC causes desensitization of capsaicin-sensitive afferent neurons and reduces GMBF, which may result in the production of gastritis.

Animals↗
PubMed1995

Enhanced gastric mucosal damage in rats after chronic treatment with sodium taurocholate.

We examined whether or not 4-week treatment with 10 mM sodium taurocholate (TC) weakens the mucosal defensive mechanism in rat stomachs. The ex vivo stomachs of anesthetized animals were perfused with 100 mM HCl. In the control tap water group, mucosal application of 10 mM TC dissolved in 100 mM HCl for 30 min caused a marked increase in gastric mucosal blood flow (GMBF), a reduction in transmucosal potential difference (PD), acid loss and visible mucosal damage. In the TC group, however, acidified TC applied for 30 min caused only a slight increase in GMBF, a reduction in PD, significant acid loss and severe mucosal damage. These results indicate that the mucosal defensive mechanism was extensively weakened after chronic treatment with TC.

Action Potentials↗
PubMed1995

[Allogenic bone marrow transplantation for Fanconi's anemia with leukemic transformation from an HLA identical father].

We report a case of a 19-year-old male with congenital aplastic anemia and multiple abnormalities; short stature, hypoplastic thumb, skin pigmentation and mental retardation. He was admitted to our hospital because of severe pancytopenia. Bone marrow aspiration showed markedly hypocellular marrow with 42% myeloblasts. He was diagnosed as AML (M2) transformed from Fanconi's anemia and underwent allo-BMT from an HLA-identical father. The conditioning regimen consisted of high dose Ara-C, high dose etoposide and 12Gy fractionated total body irradiation. Severe toxicity associated with the conditioning regimen was not observed. Cyclosporin A and short-term methotrexate were administered for prophylaxis of acute GVHD. Neither acute nor chronic GVHD were observed. He is well and free of disease for 15 months since BMT. Very few cases of Fanconi's anemia with leukemic transformation treated by BMT have been reported. Long-term observation will be necessary to evaluate our conditioning regimen for Fanconi's anemia with leukemic transformation.

Adult↗
PubMed1995

Neutrophil chemotactic N-acetyl peptides from the calpain small subunit are also chemotactic for immunocytes.

N-terminal peptides from the calpain small subunit were shown to have dose-dependent chemotactic activity toward several types of leukemia cells: T cell, B cell, monocyte and granulocyte/monocyte line leukemia cells. In order to prove that chemotaxis is mediated via receptors, a fluorescein-labeled probe was prepared from one of the N-terminal peptides and its interaction with peripheral leukocytes was estimated by means of flow cytometry, resulting in staining not only of neutrophils but also of most of the monocytes and more than half of the T and B lymphocytes. The results indicate that calpain-derived N-terminal peptides may be involved in defense mechanisms, inducing chemotaxis of immunocytes as well as that of neutrophils.

Amino Acid Sequence↗
PubMed1995

[Fatty acid metabolism in patients with idiopathic dilated cardiomyopathy: characteristics and prognostic implications].

The characteristics of myocardial fatty acid metabolism in patients with idiopathic dilated cardiomyopathy (DCM) were investigated by myocardial imaging with beta-methyl-p-[123I]iodophenyl-pentadecanoic acid (BMIPP) in 16 patients with DCM, 8 patients with hypertensive heart failure (HHF), and 11 normal subjects. Rest myocardial imaging with BMIPP and 201Tl was performed on another day. The index of myocardial BMIPP uptake, or uptake ratio, was calculated from the percentage uptakes of BMIPP and 201Tl. The index of inhomogeneity of intramyocardial isotope distribution was calculated as the coefficient of variation of BMIPP and 201Tl. The uptake ratio was significantly lower in DCM and HHF patients than in normal subjects (p < 0.01). Uptake ratio correlated well with fractional shortening (r = 0.76, p < 0.01), and left ventricular ejection fraction (r = 0.58, p < 0.01). Although uptake ratio was not different between DCM and HHF patients, defects in BMIPP imaging appeared more frequently in DCM (69%) than in HHF (38%) patients. Furthermore, the extent of the defect in BMIPP imaging in DCM patients was larger than that in 201Tl imaging (p < 0.05), but in HHF patients the extent of the defects in both methods was similar. The coefficient of variation of BMIPP in DCM patients was greater than those in HHF patients and in normal subjects, but those of 201Tl were not different between the three groups. The coefficient of variation of BMIPP in DCM patients correlated well with serum norepinephrine level (r = 0.57, p < 0.01) and atrial natriuretic peptide (r = 0.77, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Primary gastric Hodgkin's disease. Morphologic, immunohistochemical, and immunogenetic analyses.

Two cases of primary gastric Hodgkin's disease were examined morphologically and immunohistochemically. Immunogenetic studies were also made in one of the cases. Case 1 was diagnosed as nodular sclerosis and case 2 as mixed cellularity Hodgkin's disease. Large atypical mononuclear or multinucleated giant cells were immunohistochemically positive for BerH2, whereas they were negative for LCA, L26, DAKO CD3, MT1, UCHL-1, S100 protein, and MAC387. In case 1, large atypical cells examined immunohistochemically on frozen tissue specimens were positive for Ki-1 and negative for T- and B-cell markers. Southern blot hybridization studies performed on material from case 1 revealed germline configuration of immunoglobulin JH and T-cell-receptor beta-chain genes. To our knowledge, this is the first report in which primary gastric Hodgkin's disease has been studied immunogenetically. Although rare in incidence, the existence of Hodgkin's disease in the stomach must be noted.

Aged↗
PubMed1994

A protein kinase inhibitor, H-7, inhibits the development of tolerance to opioid antinociception.

To investigate the effect of a protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), on the development of tolerance to antinociception induced by morphine (mu-opioid receptor agonist) and butorphanol (mu/delta/kappa-mixed opioid receptor agonist), rats were infused i.c.v. with morphine, butorphanol and H-7 through osmotic minipumps for 3 days. Concomitant infusion of H-7 dose dependently inhibited the development of tolerance to i.c.v. morphine- and butorphanol-induced antinociception. These results suggest that protein kinases may play an important role in the development of opioid tolerance.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗