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T Ooka

Publications and source records attributed to T Ooka.

At least 73 records · Page 4Linked to original sources

[A case of bromocriptine-induced interstitial pneumonitis in an iron factory worker exposed to sand dust].

A 62-year-old male, was admitted on Oct. 7, 1987 because of productive cough and dyspnea. He worked for an iron factory, where pneumoconiosis was regarded as an occupational disease, for 40 years. No abnormal finding had been noted on his mass screening chest roentgenograms. He was well until three years ago when hypertension and Parkinsonism were noted. Since then he was treated with beta blockers, L-DOPA, amantadine and bromocriptine. Two weeks before admission, he suddenly complained of dyspnea and productive cough. His chest roentgenograms showed diffuse reticulonodular infiltration in both lung fields. The partial pressure of oxygen of the arterial blood was 65.9 Torr. The first transbronchial lung biopsy obtained from right B8 on Sept. 29, 1987 (before the admission) revealed some epithelioid granulomas and the second biopsy obtained from right B10 on Oct. 14, 1987 demonstrated bronchiolar edema and infiltration of inflammatory cells. Fibrotic changes associated with carbon dust between airways and vessels were also noted. Lymphocyte stimulation index by bromocriptine was 362%, and that by amantadine, 139%, L-DOPA, 150%, respectively. After ceasing the administration of bromocriptine, productive cough, dyspnea and the reticulonodular shadows diminished gradually. These findings strongly suggest that the interstitial pulmonary lesions are bromocriptine-induced interstitial pneumonitis. His occupational exposure to inorganic dust may be a predisposing factor.

Bromocriptine↗

[A case of breast cancer with multiple metastases to the lung and bone responding well to cisplatin and vindesine].

A case of recurrent breast cancer with metastases to the lung and bone responding well to cisplatin and vindesine in a 45-year-old woman was reported. She had a radical mastectomy for the right breast cancer (pT2N0M0) at 28 years old. She was well until March 1985, when right iliac bone pain appeared. Osteolytic changes were noted on her pelvic roentgenogram. A biopsy obtained from the right iliac bone revealed metastatic adenocarcinoma. She was admitted to our hospital in December 1985 because of chest pain and swelling of the left axillary lymph nodes. Lymph nodes also showed metastatic adenocarcinoma with positive estrogen receptor. Her chest roentgenogram demonstrated a coin lesion in the left hilum and also left pleural effusion. Cytology of the effusion revealed adenocarcinoma. She was first treated with Adriamycin, 5-FU and Cyclophosphamide, but no significant response was noted. But, after two courses of chemotherapy containing cisplatin (80 mg/m2) and vindesine (3 mg/m2), the coin lesion of the lung and pleural effusion disappeared. The osteolytic bone change of the pelvic bone also improved. The serum CEA level decreased from 34.2 ng/ml to 4.2 ng/ml. These results suggest that cisplatin and vindesine were effective for lung and bone cancers metastatic from adenocarcinoma of the breast.

Adenocarcinoma↗

Altered expression of two Epstein-Barr virus early genes localized in BamHI-A in nonproducer Raji cells.

The Epstein-Barr virus-carrying lymphoblastoid cell line Raji has two major genomic deletions and is incapable of virus production. Two cDNA clones, c70 and c55, were constructed from early mRNA of P3HR-1 cells and localized, respectively, in BALF-2 and BARF-1 open reading frames where one of the major genomic deletion in Raji cells is situated. These were used to search the different early viral transcripts in producer P3HR-1 and nonproducer Raji lines. c70 and c55 hybridized with their corresponding mRNAs only in producer lines. Analysis with in vitro-synthesized RNA probes showed quite a different transcriptional profile in Raji cells than in P3HR-1 cells. In the P3HR-1 line, BALF-2 encodes a 3.4-kilobase (kb) mRNA during the early phase and a 3.3-kb mRNA during the late phase, and in the Raji line, the probe corresponding to BALF-2 hybridized with three mRNAs of 5.0, 3.1, and 2.4 kb; in P3HR-1 cells, BARF-1 encodes a group of 3'-conterminal transcripts (0.8, 1.2, 1.7, 2.7, 3.2, and 5.0 kb) during both the early and late stages; in Raji cells, however, 0.8-, 1.2-, and 1.7-kb mRNAs are absent, the only mRNAs transcribed being upstream of the deletion and of 5.0, 2.6, and 2.0 kb in size. In vivo and in vitro experiments demonstrated that the BALF-2 open reading frame encodes an early 135-kilodalton (kDa) protein which possesses DNA-binding ability and can be recognized by a herpes simplex virus ICP-8 antiserum. The BARF-1 open reading frame encodes in vitro a 26- to 33-kDa early protein recognized by anti-EA serum. The proteins of both two genes expressed in psi AM 22b cells were localized in nuclei. According to their properties, both proteins, particularly the BALF-2-encoded 135-kDa DNA-binding protein, could play a role in virus replication.

Cell Line↗

Identification of an Epstein-Barr virus-specific desoxyribonuclease gene using complementary DNA.

We have recently obtained 18 distinct cDNA clones representing different genes expressed in the early phase of EBV infection. One of them, c37, which is situated at the position 12907-122451 in the B95-8 viral genome, is shown here to code for a viral desoxyribonuclease [DNase]. Cell free translation of c37-selected messenger RNA yielded a protein of about 52 KDa which was immunoprecipitated by a high EA titer serum from nasopharyngeal carcinoma patient. This protein showed a DNase activity which was resistant to high salt concentrations (150 to 300 mM KCl) and was specifically neutralized by EA positive serum. These properties are typical of the EBV-specific DNase activity that we recently described in chemically induced EBV-transformed lymphoid cells. The same results were obtained on cell-free translation of the native RNA synthesized in vitro from pGEM-37 plasmid containing the entire c37 cDNA sequence (1.53 Kb). These data indicate that the BGLF5 open reading frame contained in c37 encodes for the EBV-specific DNase.

Base Sequence↗

Epstein-Barr virus glycoprotein homologous to herpes simplex virus gB.

The Epstein-Barr virus DNA open reading frame BALF4 (R. Baer, A.T. Bankier, M.D. Biggin, P.L. Deininger, P.J. Farrell, T.J. Gibson, G. Hatfull, G.S. Hudson, S.C. Stachwell, C. Sequin, P.S. Tuffnell, and B.G. Barrell, Nature [London] 310:207-211, 1984), which by nucleotide sequence comparison could encode a protein similar to herpes simplex virus gB (P.E. Pellett, M.D. Biggin, B. Barrell, and B. Roizman, J. Virol. 56:807-813, 1985), has now been shown to encode a 110-kilodalton glycoprotein. Late infectious cycle RNAs of 3.0 and 1.8 kilobases are transcribed from BALF4. Translation of these RNAs in vitro, transcription and translation of BALF4 in vitro, or metabolic labeling of cells in the presence of tunicamycin and immunoprecipitation with BALF4-specific sera results in identification of a 93-kilodalton precursor to gp110. Since N-glycosidase F only reduces the size of gp110 to 105 kilodaltons, gp110 probably has both N- and O-linked glycosylation, gp110 is an abundant glycoprotein in Epstein-Barr virus-infected cells. In infected lymphocytes and in 3T3 cells, in which the gene is expressed from a recombinant expression vector, most of the protein is cytoplasmic and perinuclear. In contrast to gB, gp110 was not detected in the infected-cell plasma membrane. In cells replicating Epstein-Barr virus, gp110 localized to the inner and outer nuclear membrane lamellae and to endoplasmic reticulum structures which sometimes contained enveloped virus. gp110 may play an important role in modifying infected intracellular membranes.

Amino Acid Sequence↗

Characterization of an Epstein-Barr virus-induced thymidine kinase.

Previous work from our laboratory suggested that the selective inhibition of Epstein-Barr virus (EBV) replication by 1-beta-D-arabinofuranosylthymine in human lymphoid cell lines involved the induction of a new thymidine kinase (TK) able to phosphorylate the thymidine analog. We further characterized this enzyme induced in various EBV-positive cell lines after viral genome activation with a combination of sodium butyrate and 12-O-tetradecanoylphorbol-13-acetate. The following results confirmed the existence of an EBV-specific deoxypyrimidine kinase: induction of EBV-related TK was connected with the appearance of viral early antigens in EBV-carrying cells; unexpected behaviors of the enzyme activity upon different fractionating treatments led to the conclusion that EBV-induced TK was extracted as a complex molecular form, larger than other known cellular or viral isozymes; enzymatic properties distinguished EBV-induced TK from host lymphoid cell isozymes but made it resemble other herpesvirus-specific deoxypyrimidine kinases, i.e., by partial inhibition by dTTP or ammonium sulfate, insensitiveness to dCTP, and nonstringent specificity for normal TK substrates. Genetic evidence is required to definitively ensure that EBV-specific TK actually is virus coded in EBV-transformed human lymphoid cells.

Antigens, Viral↗

Epstein-Barr virus-specific DNA polymerase in virus-nonproducer Raji cells.

Virus-nonproducer Raji cells, when induced to early antigen synthesis by 12-O-tetradecanoyl-phorbol-13-acetate and sodium butyrate, showed an increase in DNA polymerase activity. This enzyme has the characteristics of a typical Epstein-Barr virus DNA polymerase with regard to chromatographical pattern and biological properties: it is eluted from DEAE-cellulose at 0.08 M NaCl, has a high salt resistance, is sensitive to phosphonoacetic acid and phosphonoformate, and shows a substrate preference for poly(dC)-oligo(dG12-18). The resistance of Epstein-Barr virus polymerase activity to aphidicolin is a property distinct from that of HSV DNA polymerase. Viral DNA polymerase activity increases in the absence of Epstein-Barr virus DNA replication, indicating that this enzyme is an early viral protein.

Antigens, Viral↗

Construction and use of cDNA clones for the mapping and identification of Epstein-Barr virus early P3HR-1 mRNAs.

cDNA clones, specific for early Epstein-Barr virus (EBV) RNAs, were constructed from total cytoplasmic RNA of P3HR-1 TK- cells. From 10,000 cDNA clones screened, 22 virus-specific cDNA clones were selected by hybridization with a total EBV DNA. These clones were then precisely mapped on the EBV genome and the corresponding mRNAs were identified by Northern blot hybridizations. Most of them are clearly related to some of the open reading frames described by Baer et al. (Nature [London] 310:207-211, 1984). They represent at least 18 different genes active during the early viral cycle. The transcriptional activity of the virus during the early stage was also studied by dot blot hybridization of total early cDNA probe to EBV genomic fragments. Three main regions showed very strong hybridization with the cDNA probe: BamHI a, M, and L fragments, BamHI K, B, and G fragments, and BamHI B1 fragment (deleted in strain B95-8) and the adjacent right end of the DNA molecule. Seventeen of the cDNA clones were localized in these highly transcribed regions. The five others were dispersed all along the EBV genome.

Animals↗

The molecular biology of Epstein-Barr virus.

Epstein-Barr virus (EBV) was discovered in continuously growing tumor cells derived from African patients with Burkitt's lymphoma. In the intervening twenty years, much biological and biochemical information has been accumulated. The virus infects B lymphocytes and occupies a unique position among human herpesviruses in that it is the only one which is capable of forming a latent infection whereby complete copies of the virus genome persist in growth transformed cells. Since there are no fully permissive cell systems of virus replications, only the established B cell lines are available for study of the molecular events of EB virus in infected cells. A viral cycle consists of four stages, latent, early replicative, middle replicative and late replicative stages. In the latent state, only small parts of the viral genome are transcribed and express transformation proteins: nuclear antigens (EBNAs) and lymphocyte determined membrane antigen (LYDMA). After reactivation of viral genome and during a productive cycle, more than 50 RNAs are expressed and over 30 viral-specified polypeptides are detectable by immunoprecipitation with a high titer human anti-EBV serum. During the early replicative stage, early antigens (EA) and DNA enzymes, both necessary for DNA synthesis, are synthesized. In the late replicative stage, about 30-40 mRNA are transcribed and two major late antigen complexes, viral capsid antigens (VCA) and membrane antigens (MA), are identified. These antigens are indispensable for the formation of virions.

Animals↗

Inhibition of human and woodchuck hepatitis virus DNA polymerase by the triphosphates of acyclovir, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine and E-5-(2-bromovinyl)-2'-deoxyuridine.

The triphosphates of acyclovir (ACV), 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) and E-5-(2-bromovinyl)-2'-deoxyuridine (BVdU) have been examined for their inhibitory effects on the endogenous DNA polymerase reactions of human hepatitis B virus (HBV) and woodchuck hepatitis virus (WHV). All three triphosphates (ACVTP, FIACTP and BVdUTP) inhibited the HBV and WHV DNA polymerases by competing with the corresponding natural substrates. FIACTP was the most potent inhibitor of HBV and WHV DNA polymerase while ACVTP was the least effective inhibitor. The inhibitory properties of these compounds were compared with those of the 5'-triphosphates of 1-beta-arabinofuranosyl-cytosine (ara-CTP) and 1-beta-arabinofuranosylthymine (ara-TTP). The 50% inhibitory doses for HBV and WHV DNA polymerases were in the following order: FIACTP less than BVdUTP less than ara-TTP less than ACVTP less than ara-CTP. BVdUTP appeared to be an efficient alternate substrate to dTTP for HBV DNA polymerase while FIACTP was much less efficient when substituted for dCTP. ACVTP did not act as an alternate substrate to dGTP and appeared to prevent DNA chain elongation.

Acyclovir↗

Comparison of properties of woodchuck hepatitis virus and human hepatitis B virus endogenous DNA polymerases.

The principal properties of the DNA polymerases of woodchuck hepatitis virus and human hepatitis B virus were compared. The enzymes of both viruses exhibited optimal activities in the same range of pH, ionic strength, and MgCl2 concentration. Like human hepatitis B virus DNA polymerase, the woodchuck hepatitis virus DNA polymerase was strongly inhibited by phosphonoformic acid but not by phosphonoacetic acid and aphidicolin. Similar inhibition patterns for both enzymes were observed with arabinofuranosyl nucleotides (9-beta-D-arabinofuranosyladenine-5'-triphosphate, 1-beta-D-arabinofuranosylcytosine-5'-triphosphate, 1-beta-D-arabinofuranosylthymine-5'-triphosphate) and dideoxythymidine triphosphate, whereas no effect was obtained with corresponding nucleosides. The therapeutic significance of these results and the relevance of the woodchuck as an experimental animal model for the study of human hepatitis B virus infections are discussed.

Animals↗

Epstein-Barr virus-specific DNase activity in nonproducer Raji cells after treatment with 12-o-tetradecanoylphorbol-13-acetate and sodium butyrate.

An Epstein-Barr virus (EBV)-specific DNase was induced in EBV nonproducer Raji cells after treatment with 12-O-tetradecanoylphorbol-13-acetate and sodium butyrate. The increase in EBV DNase activity was related to the appearance of early antigen-positive cells. The enzyme had a sedimentation coefficient of 4S and was resistant to 300 mM KCl, and its induction did not depend on viral DNA synthesis. The EBV-specific DNase activity was specifically inhibited by sera from patients who had nasopharyngeal carcinoma with high early antigen activities but not by sera from normal, healthy individuals. There was a correlation between the degree of anti-EBV DNase activity and the titers of early antigen antibody.

Antigen-Antibody Complex↗

Effect of arabinofuranosylthymine on the replication of Epstein-Barr virus and relationship with a new induced thymidine kinase activity.

1-beta-D-Arabinofuranosylthymine (araT) is a selective inhibitor of Epstein-Barr virus replication induced in both thymidine kinase (TK)-negative (TK-) and TK+ variants of the lymphoid cell line P3HR-I. This analog has no effect on the growth of noninduced cells (T. Ooka and A. Calender, Virology 104:219-223, 1980). The synthesis of early antigens is not affected by the analog, whereas that of late viral capsid antigens is completely inhibited, as demonstrated by the indirect immunofluorescence technique; kinetic reassociation experiments have also shown that araT strongly inhibits replication of viral DNA. Phosphorylation of the tritiated form of the analog ([3H]araT) was analyzed by thin-layer chromatography in cultures of control and induced cells, and the results demonstrated that only induced cells can convert the analog to the triphosphate form. These results indicate that the selective effect of araT in induced cells is probably related to a new virally induced TK activity. Preliminary characterization of this new activity has shown that it is able to phosphorylate the analog specifically, whereas cellular TKs cannot. araTTP, a final phosphorylation product of araT, is a potent inhibitor of Epstein-Barr virus-specific DNA polymerase, suggesting a possible inhibitory action of this product on Epstein-Barr virus replication.

Antigens, Viral↗

Lipid peroxidation in alcoholic liver disease in humans.

The lipoperoxide level in liver as well as serum in alcoholic patients was measured by using the thiobarbituric acid method. Heavy drinkers with deposition of fat in liver had a significantly (p less than 0.001) higher level of hepatic lipoperoxide examined in about 7 days after abstinence than did nonalcoholic individuals with histologically normal liver. Of these heavy drinkers, cases with a remarkably high level of liver lipoperoxide showed a high incidence of hepatic cell necrosis. The hepatic lipoperoxide level was correlated with the serum lipoperoxide level in these heavy drinkers (r = 0.750, p less than 0.001). In chronic alcoholics, high levels of serum lipoperoxide were usually observed on admission, and a significant positive correlation was found between the serum lipoperoxide level and serum GOT activity (r = 0.541, p less than 0.01). After a 2-wk abstinence, the levels of serum lipoperoxide decreased, which was associated with improvement of liver function tests. These results suggest a possible involvement of lipid peroxidation in alcohol-induced liver damage in humans.

Adult↗

Three main coronary arteries to pulmonary artery fistula.

A case of a 19-year-old woman with coronary artery fistula was reported. She was asymptomatic throughout her life. Physical examination revealed a continuous murmur along the left sternal border. Echocardiograms and left ventriculograms showed mitral valve prolapse. Selective coronary arteriograms disclosed arteriovenous fistula between branches of the right, the left anterior descending and the left circumflex coronary artery and the main pulmonary trunk. We believe that this is the first case report of an unusual form of anomalous coronary-pulmonary artery communication: three main coronary vessels participate in the fistula.

Adult↗