Biomedical subjects

M Imoto

Publications and source records attributed to M Imoto.

At least 55 records · Page 3Linked to original sources

PubMed1997

[A fatal case of overwhelming postsplenectomy infection syndrome developing 10 years after splenectomy].

UNLABELLED: Splenectomized patients are likely to suffer from severe infections, such as sepsis and meningitis. This syndrome is called overwhelming postsplenectomy infection (OPSI) in Europe and America. The course is rapid, the clinical symptoms are serious, and the prognosis is very poor. We treated one adult patient with OPSI syndrome that developed 10 years after splenectomy. CASE: A 26-year-old man had undergone a splenectomy following a traffic accident 10 years previously. On January 7, 1996, he had diarrhea and nausea. On January 10, he became drowsy and presented at our hospital with multiple organ failure. He underwent hemodialysis and plasmapheresis because of acute renal failure and also received immune globulin, antibiotics and prednisolone. However, these medications were not effective. He died 7 hours later. We identified diplococcus on a blood smear, IgG 3 deficiency and a low titer of specific pneumococcal IgG 2 antibody. The autopsy findings included bilateral acute hemorrhagic necrosis of the adrenal glands (Waterhouse-Friderichsen syndrome).

Adult↗

PubMed1997

[Screening of phosphatidylinositol turnover inhibitors and regulation of cell cycle progression].

Phosphatidylinositol (PI) turnover is considered to be involved in the regulation of cell growth. The enzymes for PI turnover include phospholipase C (PLC), PI4-kinase and PI synthase. We have isolated pholipeptin and fluvirucin B2 from microorganisms and akaterpin from a marine sponge as PLC gamma inhibitors. We also isolated echiguanines from Streptomyces as PI4-kinase inhibitors. Since echiguanines did not inhibit the enzyme in situ, we synthesized their ribosylated derivatives that were effective in cultured cells. We previously isolated inostamycin from Streptomyces as an inhibitor of PI synthase. We found that inostamycin induced G1 block in cycling NRK cells. Inostamycin inhibited the serum-induced S-phase induction in quiescent NRK cells. Inostamycin was found to decrease serum-induced expression of cyclin D and cyclin E, without inhibiting the activation of MAP kinase. It also inhibited serum-induced activation of CDK2 and phosphorylation of pRB. Thus, PI synthesis was suggested to be involved in regulation of serum-induced S-phase induction by modulating G1 cyclin expression.

Animals↗

PubMed1996

Involvement of hydrogen peroxide production in erbstatin-induced apoptosis in human small cell lung carcinoma cells.

Tyrosine kinase inhibitor, erbstatin, induced morphological apoptosis and DNA fragmentation in human small cell lung carcinoma (SCLC) cells. Erbstatin-induced apoptosis was inhibited by antioxidants, whereas erbstatin-inhibited tyrosine phosphorylation was not affected by them. Erbstatin was shown by means of flow cytometry to induce hydrogen peroxide generation. Furthermore, hydrogen peroxide induced morphological apoptosis and DNA fragmentation in the SCLC cells. We also demonstrated that erbstatin-induced hydrogen peroxide production and DNA fragmentation were partially suppressed by inhibition of protein synthesis. Thus, erbstatin-induced apoptosis would be due to hydrogen peroxide generation via newly synthesized protein.

Antioxidants↗

PubMed1996

Inhibition of G1 cyclin expression in normal rat kidney cells by inostamycin, a phosphatidylinositol synthesis inhibitor.

We previously reported that inostamycin, an inhibitor of CDP-DG: inositol transferase, inhibited cell proliferation in normal rat kidney (NRK) cells by blocking cell cycle progression at the G1 phase. In the present paper, we report the effect of inostamycin on the serum-induced activation of Ser/Thr protein kinases that are involved in G1 progression. In quiescent NRK cells mitogen-activated protein kinase (MAP kinase) and casein kinase II were activated within 15 min after serum addition. Neither activation was affected by the treatment with inostamycin. However, in the inostamycin-treated cell, cyclin-dependent kinase 2 (CDK2) failed to be activated after serum stimulation. Since serum-induced expression of cyclin E was also suppressed by inostamycin, this inhibitor would appear to block CDK2 activation by inhibiting cyclin E expression. Furthermore, inostamycin also inhibited cyclin D1 expression induced by serum; and consequently, hyperphosphorylation of retinoblastoma protein (pRB) by RB-kinases such as CDK4 and CDK2 was abolished, which would result in elimination of functional inactivation of pRB. Thus, early G1 arrest in NRK cells by inostamycin is due to the inhibition of cyclin D1 and E expressions.

Animals↗

PubMed1996

Idiopathic adulthood ductopenia.

In 1981, a 26 year old man occasionally demonstrated elevated serum transaminase concentrations. He had no history of medication, or a personal or family history of jaundice, except for prolonged physiological jaundice as a neonate. Serum hepatitis B surface antigen, hepatitis C virus antibody and anti-mitochondrial antibody were absent. A wedge biopsy specimen revealed ductular proliferation, mild inflammation of the portal area and disappearance of bile ducts from 80% of the portal tracts. Serial sections demonstrated a vanishing bile duct. Endoscopic retrograde choledochopancreatography, portography and arteriography demonstrated no abnormalities. In 1994, the patient died of hepatic failure following a 12 year observation period. He was subsequently diagnosed with idiopathic adulthood ductopenia on the basis of the criteria proposed by Ludwig.

Adult↗

PubMed1996

A long-term follow-up study of interferon treatment for chronic hepatitis C in Japanese patients with congenital bleeding disorders.

Twenty-one HIV negative Japanese patients with chronic hepatitis C who had congenital bleeding disorders, 15 hemophilia A, 3 hemophilia B, 1 von Willebrand's disease, 1 afibrinogenemia and 1 thrombasthenia, were treated with 9 million units 3 times a week of natural interferon (IFN)-alpha for 6 months. They were followed, biochemically and virologically, for at least 18 months after therapy discontinuation to evaluate the long-term results. Liver biopsy, hepatitis C virus (HCV) genotyping and quantification of viral load by polymerase chain reaction (PCR) were performed to identify the predictors of a favorable response to IFN treatment. One male patient with hemophilia A dropped out because of general fatigue and was excluded from evaluation. Ten (50.0%) patients continued to be HCV RNA negative in serum together with normal ALT levels throughout the study. Subtype 1b and a high level of viremia significantly associated with an unfavorable outcome on the response to IFN although liver histology was not definitive for predicting the response. We concluded that a 6-month treatment with high doses of natural IFN-alpha was effective in inducing a long-term response without relapse of viremia in 50% of chronic hepatitis C patients with congenital bleeding disorders and that HCV subtype and pretreatment level of viremia were useful predictors of the response to IFN in treating such patients.

Adolescent↗

PubMed1995

Such hydrophobic peptides as dansylated mastoparan can elevate the fertilization membrane of sea urchin eggs.

Melittin is known to be a major hydrophobic peptide component in honeybee venom that can cause as much elevation of fertilization membrane of sea urchin eggs as normal fertilization. The action of melittin has been thought to be closely related with its ability to facilitate the phospholipase A2 activity on the eggs. However, another peptide "mastoparan" from wasp venom was not found here to cause any elevation of the membrane, although it can activate the enzyme as well as melittin. On the other hand, mastoparan was found to get the membrane-elevating activity only when its amino groups were modified with hydrophobic substituents. N epsilon-Substituted mastoparan with a dansyl group in Lys11 residue was most effective among the analogs examined here. Our findings indicate that the facilitation of phospholipase by the peptides have little relation with the membrane generation. Such hydrophobic moiety as the dansyl group in the peptides must cause the cortical reaction on the eggs in cooperation with peptide moiety. The dansylated peptide will be a useful tool to induce the artificial fertilization of sea urchin eggs.

Amino Acid Sequence↗

PubMed1995

Induction of erythroid differentiation in leukaemic K562 cells by an S-adenosylhomocysteine hydrolase inhibitor, aristeromycin.

We have isolated an unusual nucleoside, aristeromycin, from the culture filtrate of Actinomycetes as a compound that induces normal morphology in v-ablts-NIH3T3 cells. Aristeromycin also induced erythroid differentiation in abl-expressing human chronic myelogenous leukaemia K562 cells. It did not affect the amount of Abl or the Abl-associated tyrosine kinase activity in either v-ablts-NIH3T3 or K562 cells. As a potent inhibitor of S-adenosylhomocysteine hydrolase, aristeromycin inhibited methylation of phosphatidylethanolamine to form phosphatidylcholine in K562 cells. Among aristeromycin analogues, the activity to inhibit S-adenosylhomocysteine hydrolase was paralleled with the induction of erythroid differentiation. Thus, aristeromycin inhibits abl functions indirectly, possibly by inhibiting biological methylations.

3T3 Cells↗

PubMed1995

Hepatitis C virus infection and genotypes in Japanese hemophiliacs.

Liver function and antibodies to hepatitis C virus and to human immunodeficiency virus-1 were examined in 195 Japanese patients with hemophilia. One hundred and seventy-three were positive for antibody to HCV and 61 for antibody to human immunodeficiency virus-1. In 63 patients, we examined HCV genotypes according to the double polymerase chain reaction method. Forty cases (63%) were infected with hepatitis C virus with a single genotype, including type 1a in five, type 1b in 21, type 2a in seven and type 2b in seven; 16 (25%) were infected with double genotypes, including types 1a + 1b in 14, types 1b + 2a in one and types 1b+2b in one; and four (6%) were infected with triple genotypes, including types 1a + 1b + 2b in two. Genotype could not be determined in three patients by this method. In the 191 nonhemophiliac patients with chronic hepatitis C, HCV genotyping was as follows: type 1a in 0, type 1b in 121, type 2a in 40 and type 2b in 10 of 171 cases (89.5%) with single infection and types 1b + 2a in five and types 2a + 2b in one of six (5.5%) with double infection. In the remaining 14 patients, genotype could not be determined. Frequent transfusion of domestic and/or imported coagulation factor concentrates probably caused the high incidence of HCV infection with rare or mixed genotypes in Japanese hemophiliacs.

Adolescent↗

PubMed1995

Effects of ajmaline on non-sodium ionic currents in guinea pig ventricular myocytes.

The lack of currently available data stimulated us to investigate the electrophysiological effects of ajmaline, a classical class Ia antiarrhythmic agent, on various currents responsible for the action potential plateau and repolarization phases. The whole cell patch clamp recording technique was applied to guinea pig ventricular myocytes. Ajmaline suppressed the Ca2+ current (Ica) in a dose-dependent manner (Kd = 1.2 x 10(-5) M) without affecting the steady-state inactivation kinetics and the voltage dependency of the current-voltage relationship. Ajmaline inhibited the inward portion of the inward rectifying K+ current (IKl). Ajmaline decreased the delayed rectifier K+ current (IK) without altering the activation or deactivation time courses. All these inhibitory effects of ajmaline prolonged the action potential duration in a dose dependent manner. The inhibitory actions of ajmaline on the action potential upstroke and various currents responsible for the plateau and repolarization may contribute to the observed suppression of depolarization-induced abnormal automaticities by this agent.

Action Potentials↗

PubMed1995

Inhibition of phosphatidylinositol-specific phospholipase C activity by fluvirucin B2.

We isolated fluvirucin B2 from the culture broth of Streptomyces as an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC). It inhibited PI-PLC of A431 cell cytosol with an IC50 of 1.6 micrograms/ml. Fluvirucin B2 also inhibited PI-PLC in cultured A431 cells, whereas it did not inhibit phosphatidylinositol synthesis and macromolecular synthesis markedly. It also inhibited epidermal growth factor-induced rapid rounding of A431 cells, in which PI turnover is involved.

Cells, Cultured↗

PubMed1994

Enhancement of CDP-DG:inositol transferase activity in src- and erbB2-transformed cells.

Phosphatidylinositol (PI) synthesis was activated in Rous sarcoma virus-infected NIH3T3 or activated erbB2-transformed NIH3T3 cells. The in vitro activity of CDP-DG:inositol transferase prepared from these cells was also higher than that from normal parent NIH3T3 cells, although phospholipase C and PI kinase activities were not significantly different among these cells. A tyrosine kinase inhibitor, erbstatin, inhibited the PI synthesis in cultured cells, suggesting that Src and ErbB2-associated tyrosine kinases are involved in activation of CDP-DG:inositol transferase in these cell lines.

1-Phosphatidylinositol 4-Kinase↗

PubMed1994

Involvement of phosphatidylinositol synthesis in the regulation of S phase induction.

The addition of serum to quiescent normal rat kidney (NRK) cells induced phosphatidylinositol (PI) synthesis after 4 h and DNA synthesis after 16 h. Inostamycin, an inhibitor of CDP-DG:inositol transferase, added within 4 h, inhibited both the serum-induced PI synthesis and S phase entry. By contrast, inostamycin added 8 h after release from quiescence did not inhibit the S phase entry. Inostamycin did not affect the G2/M/G1 transition, and incubation with inostamycin induced cell synchronization at early G1 phase. Thus, PI synthesis is involved in the regulation of S phase induction.

Animals↗

PubMed1994

Localization of synaptophysin immunoreactivity in the human liver.

The distribution of synaptophysin, specifically located in nerve terminals, was investigated immunohistochemically in normal and diseased human livers in 4 patients with normal liver, 6 with chronic active hepatitis, 12 with cirrhosis, and 8 with hepatocellular carcinoma. In normal liver and chronic hepatitis synaptophysin immunoreactivity was detected in the lobules and portal areas. In cirrhosis it was found in the fibrous septum but in no pseudolobules. Parenchymal innervation would thus appear to cease with the development of cirrhosis, and denervation from the parenchyma may lead to various functional abnormalities in liver cirrhosis. In hepatocellular carcinoma no synaptophysin immunoreactivity was found along carcinomatous sinusoids. Immunoreactive spots were present in the capsules of hepatocellular carcinoma to a much lesser extent than in the fibrous septum of cirrhosis. Neural functions may thus have little effect on the microcirculation of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

PubMed1994

Antitumor effect of piericidin B1 N-oxide.

Piericidin B1 N-oxide was isolated from a culture broth of Streptomyces sp. as a novel inhibitor of phosphatidylinositol (PI) turnover. Piericidin B1 N-oxide specifically inhibited orthophosphate labeling of PI induced by epidermal growth factor (EGF) without affecting the formation of phosphatidic acid (PA). Like piericidins A1 and B1, piericidin B1 N-oxide inhibited ATP synthesis in A431 cells; however, the effect of piericidin B1 N-oxide on PI synthesis was stronger than that of piericidins A1 and B1. At the concentration inhibiting PI synthesis, piericidin B1 N-oxide showed no inhibitory effect on DNA, RNA, or protein synthesis. We also demonstrated that piericidin B1 N-oxide reversibly inhibited the growth of A431 cells in situ and suppressed the growth of Ehrlich carcinoma in vivo when administered to mice by intraperitoneal (ip) injection.

Adenosine Triphosphate↗

PubMed1994

Partial hepatectomy for hepatocellular carcinoma in a patient with hemophilia: a case report.

We describe successful partial hepatectomy for hepatocellular carcinoma (HCC) in a 43-year-old man with severe factor VIII deficiency (hemophilia A). Tumor size and plasma alpha-fetoprotein (AFP) decreased spontaneously prior to surgery. HCC was found in the anterior superior segment of the liver, with invasion of the diaphragm. A limited partial resection of the liver and diaphragm was performed. The administration of factor VIII during and immediately after surgery resulted in no postoperative bleeding complications. Macroscopic findings revealed hemorrhage and necrosis throughout the intrahepatic portion of the tumor. Viable HCC cells were recognized histologically in the intrahepatic tumor and infiltrating the diaphragm. In patients with hemophilia there is a tendency for HCC to hemorrhage, which may obscure the diagnosis. Appropriate administration of factor VIII permits the safe resection of HCC in hemophilia A.

Adult↗

PubMed1993

Induction of normal phenotypes in ras-transformed cells by damnacanthal from Morinda citrifolia.

We have screened tropical plant extracts for substances that induce normal morphology in K-rasts-NRK cells. As a result we isolated an anthraquinone compound, damnacanthal, from the chloroform extract of the root of Morinda citrifolia. Damnacanthal induced normal morphology and cytoskeletal structure in K-rasts-NRK cells at the permissive temperature, without changing the amount and localization of Ras. The effect of damnacanthal was reversible, and the compound had no effect on the morphology of RSVts-NRK cells expressing the src oncogene. Thus, damnacanthal is a new inhibitor of ras function.

Animals↗

PubMed1993

Isolation of a novel substrate-competitive tyrosine kinase inhibitor, desmal, from the plant Desmos chinensis.

In the course of a screening program for tyrosine kinase inhibitors, the chloroform extract of a tropical plant, Desmos chinensis, strongly inhibited the enzyme activity. The active substance was purified by silica gel, gel filtration, and finally crystallized. The structure was elucidated by mass spectrometry and X-ray crystallography to be 8-formyl-2,5,7-trihydroxy-6- methylflavanone, and we named it desmal. Desmal competed with peptide substrate and non-competed with ATP. It inhibited tyrosine kinase in situ in epidermal growth factor (EGF) receptor-overexpressing NIH3T3 (ER12) cells. It also inhibited EGF-induced inositol phosphate formation and morphological changes.

3T3 Cells↗