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Biomedical subjects

T Tsurumi

Publications and source records attributed to T Tsurumi.

At least 73 records · Page 4Linked to original sources
PubMed1987

Mechanism of inhibition of herpes simplex virus replication by delta 7-prostaglandin A1 and delta 12-prostaglandin J2.

We studied the effect of prostaglandins (PGs) A1, delta 7-A1, A2, D2, E1, E2, F2 alpha, J2 and delta 12-J2 on the replication of herpes simplex virus type 2 (HSV-2). Of nine PGs we tested, delta 7-PGA1 was found to have the most potent inhibitory effect; 50% inhibitory dose (ID50) was 0.35 microgram/ml in the plaque reduction assays and HSV-2 induced protein synthesis was strongly suppressed at 0.5 microgram/ml whereas at this dose, the protein synthesis of uninfected cells was not inhibited. Dot blot hybridization analysis revealed that delta 7-PGA1 and delta 12-PGJ2 inhibited the primary transcription of HSV-2. Thus we suggest that those PGs are primarily active at the level of mRNA synthesis.

Cell Transformation, Viral↗
PubMed1987

Nucleotide sequence of the DNA polymerase gene of herpes simplex virus type 2 and comparison with the type 1 counterpart.

The complete nucleotide sequence of the DNA polymerase gene of herpes simplex virus (HSV) type 2 strain 186 has been determined. The gene included a 3720-bp major open reading frame capable of encoding 1240 amino acids. The predicted primary translation product had an Mr of 137,354, which was slightly larger than its HSV-1 counterpart. A comparison of the predicted functional amino acid sequences of the HSV-1 and HSV-2 DNA polymerases revealed 95.5% overall amino acid homology, the value of which was the highest among those of the other known polypeptides encoded by HSV-1 and HSV-2. The functional amino acid changes were spread in the N-terminal one-third of the protein, whereas the C-terminal two-third was almost identical between the two types except a particular hydrophilic region. A highly conserved sequence of 6 aa, YGDTDS, which has been observed in DNA polymerases of HSV-1, Epstein-Barr virus, adenovirus, and vaccinia virus, was also present at positions 889 to 894 in the C-terminal region of HSV-2 DNA polymerase.

Amino Acid Sequence↗
PubMed1987

Effects of the epipodophyllotoxin VP-16-213 on herpes simplex virus type 2 replication.

It has been recently shown that VP-16-213, a semi-synthetic derivative of podophyllotoxin, inhibits the function of mammalian DNA topoisomerase II. In the present study, we examined the effects of VP-16-213 on the replication of herpes simplex virus type 2 (HSV-2). The compound did not inhibit the synthesis of early viral polypeptides at concentrations at which viral DNA synthesis was strongly suppressed, but induced double-strand breaks in newly synthesized HSV DNA. Electron microscopic examination of treated cells revealed the presence of a number of capsids with empty or partial cores. The level of topoisomerase II activity remained unaltered after infection, and all attempts to isolate VP-16-213-resistant mutants of HSV-2 have failed in spite of extensive efforts. It is suggested therefore that the mode of action of VP-16-213 may be inhibition of viral DNA synthesis by impairing the function of host cell topoisomerase II.

Animals↗
PubMed1987

A single-base change within the DNA polymerase locus of herpes simplex virus type 2 can confer resistance to aphidicolin.

An aphidicolin-resistant (Aphr) mutant of herpes simplex virus (HSV) type 2 strain 186 previously has been shown to induce an altered viral DNA polymerase that is more resistant to aphidicolin and more sensitive to phosphonoacetic acid (PAA) than is wild-type DNA polymerase. In this study the mutation responsible for the aphidicolin-resistant phenotype was physically mapped by marker transfer experiments. The physical map limits for the Aphr mutation were contained in a 1.1-kilobase pair region within the HSV DNA polymerase locus. The 1.1-kilobase-pair fragment of the Aphr mutant also conferred hypersensitivity to PAA, and DNA sequence analysis revealed an AT to GC transition within this fragment of the Aphr mutant. Analysis of the three potential open reading frames within the 1,147-base-pair fragment and comparison with the amino acid sequence of DNA polymerase of HSV type 1 indicated that the Aphr mutant polymerase had an amino acid substitution from a tyrosine to a histidine in the well-conserved region of the DNA polymerase. These results indicate that this single amino acid change can confer altered sensitivity to aphidicolin and PAA and suggest that this region may form a domain that contains the binding sites for substrates, PPi, and aphidicolin.

Animals↗
PubMed1986

Molecular cloning of herpes simplex virus type 2 DNA.

Restriction enzyme HindIII digestion of the whole genome of herpes simplex virus type 2 strain 186 yielded 10 DNA fragments with molecular weights ranging from approximately 22 X 10(6) to 1.2 X 10(6), which were cloned into the HindIII site of bacterial plasmid pACYC 184. The cloned fragments were identified by hybridization to HSV-2 virus DNA and by double digestion with restriction endonucleases. The recombinant plasmids, even if they carried DNA sequences with molecular weights of more than 10(7), were efficiently replicated in E. coli HB101.

Chromosome Mapping↗
PubMed1986

[Abnormalities of blood coagulation and effect of anticoagulant therapy in postoperative patients with lung cancer].

To evaluate coagulable state, beta-thromboglobulin (beta-TG) levels have been followed sequentially in 70 postoperative patients with lung cancer. Nineteen out of them were treated with warfarin plus ticlopidine at a dosage enough to prolong the thrombo-test time to approximately 20% of normal value. There was a significant rise in beta-TG compared with control subjects and beta-TG was correlated with stages of disease. Serial beta-TG determinations revealed that beta-TG and CEA levels fairly paralleled with each other which suggested beta-TG might be useful in following tumor progression or response to therapy in postoperative period. As to the relation between beta-TG levels and five-year survivals, patients whose beta-TG were under 50 ng/ml showed more favorable prognoses than those who had higher levels. Long term anticoagulation with warfarin plus ticlopidine reduced the beta-TG levels of 19 stage 3 or 4 patients, especially in stage 4 the rate of reduction was marked. Nineteen patients with anticoagulant-treated group demonstrated a more prolonged time from beginning of treatment to first evidence of disease progression than 18 non-treated patients. Also anticoagulant-treated group had a more prolonged clinical course than non-treated group after disease progression. These results might be associated with disease stabilization which achieved with anticoagulant therapy. Survival at 30 months after initiation of treatment was 74% in the treated group and 64% in the nontreated group. Although there was no statistical difference in two groups, survival of treated group exceeded that of the non-treated group throughout the observation period. In stage 4 patients, however, the difference between two groups was statistically significant.

Adult↗
PubMed1984

Mechanism of interference between influenza A/WSN and B/Kanagawa viruses.

Simultaneous infection of MDCK cells with influenza viruses A/WSN and B/Kanagawa resulted in mutual interference with virus protein synthesis and in significant suppression of A/WSN growth. When infection by one virus preceded the other by 1 or 2 h, growth of the superinfecting virus was selectively inhibited at the level of transcription. Interference by the pre-infecting virus was strongly dependent on the expression of the viral genome but not on haemagglutinin activity. When the replication of both virus types was restricted to primary transcription by cycloheximide, the only translation products following removal of the drug were those of the preinfecting virus. This result was not affected by blocking secondary transcription by actinomycin D. These findings suggest that intertypic interference occurs at the level of primary transcription. This concept was supported further by the observation that a ts mutant of A/WSN (ts-65) with a defect in primary transcription interfered only with superinfection by B/Kanagawa at the permissive temperature.

Animals↗
PubMed1984

Abortive infection of L cells by influenza B virus: defect in bud formation.

Host-dependent restriction of influenza B virus replication in L cells was analysed in comparison with productive infection in MDCK or 1-5C-4 cells. The synthesis and intracellular distribution of virus-specific proteins and the production of cytoplasmic ribonucleoproteins in nonpermissive L cells were similar to those in permissive MDCK cells. However, an electron microscopic study of infected L cells showed neither extracellular virions nor budding virus particles on the cell surface, in contrast to MDCK cells which produced numerous virus particles. PAGE analysis of the plasma membrane isolated from the cells demonstrated no significant difference in the composition of viral polypeptides between permissive 1-5C-4 and nonpermissive L cells. It was noted that the abortiveness of influenza B virus infection in L cells may be due to a defect in host cell function involved in the initiation of virus budding.

Animals↗
PubMed1984

A case of chronic pancreatitis successfully treated by endoscopic removal of protein plugs.

A 56 years old male with chronic pancreatitis complained of intractable abdominal pain, anorexia, emaciation and peripheral edema. Medical treatment initiated only partial improvement in the general condition and hypoproteinemia. Endoscopic retrograde cholangiopancreatography revealed multiple filling defects in the dilated main pancreatic duct. Endoscopic aspiration of pure pancreatic juice yielded numerous protein plugs. The endoscopic removal of protein plugs from the pancreatic duct resulted in remarkable improvement in symptoms, laboratory findings and ERCP findings. We consider this procedure to be an important new treatment of chronic pancreatitis.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1983

Heat(40 degrees C)-induced polypeptides in human embryonic fibroblasts.

The synthesis of 3 polypeptides with molecular weights of 103-, 80- and 78-kdalton (K) was dramatically accelerated when the cultures of human embryonic fibroblasts were transferred from 37 to 40 degrees C. The induction of these polypeptides was not observed if actinomycin D was added to the cultures at the beginning of the rising of the temperature, indicating that this response may be mediated by increased transcription of their messenger RNA.

Female↗
PubMed1983

Effect of splenectomy and immunotherapy on advanced gastric cancer associated with total gastrectomy.

Immunotherapy with levamisole (LMS) and combined splenectomy were performed in the cases of stages III and IV gastric cancer of the upper and middle stomach and associated with total gastrectomy. The cell-mediated immunity and the survival rates for both groups were compared with controls. Combined splenectomy was not effective for cases of stage III gastric cancer, but was effective for those in stage IV. Comparing the cumulative survival rates of the immunotherapy group with the controls, cases of stages III and IV gastric cancer without splenectomy, the survival rate of those with immunotherapy was higher than that of the control group in the cases of the stage III, but the result was reverse in cases of stage IV gastric cancer. Changes in the cell-mediated immunity correlated with the survival rates.

Gastrectomy↗
PubMed1983

Identification of DNA polymerase(s) involved in the repair of viral and cellular DNA in herpes simplex virus type 2-infected cells.

When human embryonic fibroblasts (HEF) were infected with herpes simplex virus type 2 (HSV-2), replicative viral DNA synthesis and some repair synthesis of cellular DNA were induced at the early stage of infection, but almost all DNA synthesis at the late stage of infection was derived from repair synthesis of cellular and viral DNA (Y. Nishiyama and F. Rapp, Virology 110, 466-475, 1981). In this study, we have assessed the effects of DNA polymerase inhibitors on repair DNA synthesis HSV-2-infected HEF. Both viral and cellular DNA syntheses during the late stage of infection were extremely resistant to aphidicolin and phosphonoacetic acid but partially sensitive to high concentrations of 1-beta-D-arabinofuranosylcytosine, while replicative viral DNA synthesis during the early stage of infection was very sensitive to all of those inhibitors. The results suggest that neither HSV-induced DNA polymerase nor cellular DNA polymerase alpha was involved in the repair synthesis of viral and cellular DNA but that cellular DNA polymerase beta was.

Aphidicolin↗
PubMed1983

Mechanism of uncoating of influenza B virus in MDCK cells: action of chloroquine.

Exposure of influenza B virus-infected MDCK cells to chloroquine at the time of infection resulted in significant inhibition of infection. The appearance of input virus in the intracellular vesicles was not affected in the presence of the drug, but primary transcription of the virus genome did not occur. Chloroquine caused a rapid rise in the pH inside the lysosomes of MDCK cells, to 6.5 from the physiological pH 5.6. In contrast, exposure of infected cells incubated in acidic medium (pH 6.0) to chloroquine did not cause an increase in lysosomal pH and this low pH treatment during the chloroquine-sensitive phase was followed by virus production. Influenza B virus induced haemolysis of chick erythrocytes at low pH values (5.0 to 5.9) which was associated with cell-cell membrane fusion. It is likely that chloroquine prevents the uncoating of influenza B virus by increasing the lysosomal pH above the critical value required for inducing fusion between the virus envelope and the lysosomal membrane.

Animals↗
PubMed1983

Effect of high salt treatment on influenza B viral protein synthesis in MDCK cells.

Based on the information that high salt inhibits the initiation of cellular mRNA translation which depends on the function of the 5'-terminal structure of mRNA, we compared the effect of high salt on translation of host cellular mRNAs and influenza viral mRNAs, both of which are of 5'-terminal structure. Brief exposure of influenza B virus-infected MDCK cells to high salt medium resulted in a dose-dependent inhibition of viral polypeptide synthesis as well as of cellular polypeptide synthesis, but it had less effect on synthesis of viral polypeptides, particularly nonstructural protein (NS). Under these conditions the Na+ content of the infected cells was significantly increased. A similar salt effect on in vitro translation of viral and cellular mRNAs extracted from infected cells was also observed. There was no significant difference in sensitivity to hypertonic block of in vivo translation of influenza viral mRNAs and vesicular stomatitis virus mRNAs, the latter of which possess a virus-directed structure at the 5'-terminus.

Animals↗
PubMed1983

[The tumor--immunological significance of splenectomy for cancer therapy].

In animal experiment, 5 X 10(5) MH-134 tumor cells were transplanted s.c. on the back of the C3H/He mice. Three, seven, 14 and 21 days after tumor transplantation, splenectomy or sham operation were performed and the tumor growth and survival days were examined in each group. As the results, the tumor growth was inhibited and the survival days prolonged not only in the group splenectomized three days but also 21 days after tumor transplantation. Clinically, the effect of splenectomy in combination with immunotherapy on cell-mediated immunity and the survival rates were studied in the gastric cancer patients of upper and middle stomach with 90 cases of stage III and 48 cases at stage IV, totalling 138 cases who underwent total gastrectomy during 1965 and 1981. Immunotherapy was conducted with immunomodulator levamisole at a daily dose of 150 mg, three consecutive days every other week. As a result, splenectomy was not effective for advanced gastric cancer at stage III and in the patients spleen should be retained for immunotherapy. Splenectomy for gastric cancer at stage IV, particularly in combination with immunotherapy, produced augmentation of cell-mediated immunity and longer survival as well. Complications caused by splenectomy were small.

Animals↗
PubMed1982

Role of viral glycoproteins in haemolysis by influenza B virus.

Influenza B virus exhibited haemolytic activity at low pH, but the pH profile for its activity varied from strain to strain. The results of selective heat-inactivation of the enzyme activity of neuraminidase (NA) or elimination from virions of the enzyme-active portion of the NA molecule by trypsin digestion, suggest that proteolytically cleaved haemagglutinin, but not enzyme activity of NA, is essential for haemolysis by influenza B virus.

Animals↗