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Biomedical subjects

M Oguro

Publications and source records attributed to M Oguro.

At least 73 records · Page 4Linked to original sources
PubMed1986

Identification of coding regions for various Epstein-Barr virus-specific antigens by gene transfer and serology.

Baby hamster kidney cells were transfected with BamHI fragments of Epstein-Barr virus (EBV) DNA (B95-8 strain) cloned into the pLTR vector containing retroviral enhancer and promoter sequences. Seventeen fragments (BamHI-A, -B, -C, -D, -E, -G, -K, -L, -M, -O, -P, -Q, -R, -U, -V, -X, and -Z) expressed antigenically distinct EBV-specific products recognized by EBV-immune human sera.

Antigens, Viral↗
PubMed1986

Acute effects of captopril on the baroreflex of normotensive and spontaneously hypertensive rats.

When captopril was injected intravenously in urethane anesthetized rats, a hypotensive effect accompanied by bradycardia was obtained, while an intravenous (i.v.) injection of prostaglandin I2 (PGI2), which induced hypotension of the same magnitude as the hypotensive effect obtained with captopril, caused a marked tachycardia. Simultaneously, sympathetic nerve activity recorded from abdominal sympathetic nerves was unchanged following injection of captopril, while it was significantly increased during hypotension induced by PGI2. The bradycardia, but not the hypotensive effects induced by captopril was abolished by i.v. pretreatment with atropine. Intracisternal injection of a small dose of captopril inhibited reflex tachycardia during hypotension induced by PGI2 and prolonged the hypotensive effect, while intravenous administration of this dose did not inhibit the reflex tachycardia induced by PGI2. In spontaneously hypertensive rats (SHR), the hypotensive effect of captopril was increased partly, however, the accompanying bradycardia was significantly reduced. These findings suggest that captopril inhibits the baroreflex and centrally activates the cardiac vagal nerve. Moreover in SHR, the effect of captopril on cardiac vagal activity was disturbed.

Animals↗
PubMed1986

[A phase II study of epirubicin in acute leukemia: a cooperative group study].

A new doxorubicin analogue, epirubicin (EPI), has been evaluated in 11 institutions throughout Japan in a phase II study in patients with acute leukemia. A total of 41 patients were entered into this study between January 1983 and July 1985, and 34 were considered evaluable. Two patients were added for evaluation of toxicity. There were 25 males and 9 females with a median age of 43 years. Of the 34 evaluable patients, 24 had previously been treated with intensive combination chemotherapy, 21 with anthracyclines. The remaining ten were previously untreated patients. Underlying diseases were acute lymphocytic leukemia (ALL) in 15, acute non-lymphocytic leukemia (ANLL) in 17 and blastic crisis of chronic myelogenous leukemia (CML/BC) in 2. EPI was administered intravenously in two schedules, a high-dose regimen consisting of 24 to 60 mg/m2/day for 3 to 5 days and a low-dose regimen involving 11-17 mg/m2/day for 5 to 8 days. Responses were obtained in 5 (33.3%) of 15 patients with ALL, 3 of these attaining complete remission, 2 (11.8%) of 17 patients with ANLL and one (50.0%) of 2 patients with CML/BC. Out of the 21 patients who had received previous anthracyclines, 4 (19.1%) attained responses. Also, responses were obtained in 23.5% with the higher doses as well as 24% with the lower doses. The remission duration of responders was 1, 1, 3, 3, 3, 16+, 17 and 26 weeks, respectively. The major non-hematologic toxicity was stomatitis which occurred in 15 patients, in 11 of whom the symptoms were severe (Grade 3 or 4). This stomatitis was thought to be the dose limiting factor. On the basis of the above observations, we concluded that EPI was active against acute leukemia, especially ALL. Stomatitis was considered to be the dose-limiting factor, especially in the high-dose regimen. Toxicity was tolerable in the low-dose regimen.

Acute Disease↗
PubMed1986

[In vitro predictive activity assay of agents based on dynamic cellular morphological findings--clinical application].

The antitumor activity and mode of action of antitumor agents were assayed by a new method which takes a relatively short time for evaluation. The method was clinically applied to patients with malignant lymphoma or acute leukemia for estimating drug sensitivity. Fresh malignant cells were obtained from patients' bone marrow, lymph nodes, or peripheral blood using Lymphoprep methods in 26 patients with these malignant disorders. Each sample (5 X 10(5) cells/ml) was cultured in the medium with RPMI 1640 supplemented with 10% of FCS and 20% of patients' own sera containing every antitumor agent at predetermined concentrations for 30 minutes. Each sample was again cultured for another 72 hours at 37 degrees C in a 5% CO2 humidified atmosphere after rinsing. Microscopic observation was periodically carried out using a specially devised observation chamber with an inverted immersion microscope for 72 hours. Morphological changes of 200 to 300 cells of each sample were described according to morphological criteria. Of these, irreversible changes in number were considered to be indicative of antitumor activity of the agent tested. More than 50% cellular damage was categorized as effective and more than to 50% reduction of leukemia cells or decrease in size of lymph nodes the same degree in malignant lymphoma were considered to be clinically effective. Forty-four assay runs in 26 patients were done, and on 31 occasions were shown to be coincident. We conclude that this in vitro method is fully applicable for predicting the effectiveness of an agent to be clinically administered regardless of the various controversial problems to be solved.

Adolescent↗
PubMed1986

[Pharmacokinetic study of mitoxantrone].

The pharmacokinetics of mitoxantrone, an anthraquinone antitumor agent, were cooperatively investigated at 5 institutions including 4 patients with breast cancer and 3 patients with malignant lymphoma. A single dose of 10 mg/m2 was intravenously infused into 5 patients, and a 5-day schedule of repeated 4.2 mg/m2 or 3 mg/m2 was given to each of 2 patients. With single administration, the blood concentrations showed that the half-life for the alpha phase was 0.16 h, for the beta phase 1.58 h, and for the gamma phase 83.4 h. The distribution volume at steady state was 1,112 l/m2. The total body clearance was 326.8 ml/m2, showing rapid clearance from the blood. The cumulative urinary excretion in 96 h was 5.17% of the dose. With repeated administration, in one patient without third space, the pharmacokinetics were similar to those of the patients given single administration, but in the other patient with third space, lowered clearance was noted. The pharmacokinetics of mitoxantrone in the Japanese patients were nearly the same as those of European patients, and the blood concentration fitted the three-compartment model, with rapid distribution to the tissues.

Adult↗
PubMed1985

Inhibition of transcriptase activity of influenza A virus in vitro by anti-haemagglutinin antibodies.

An investigation was made of inhibition of transcriptase activity of influenza viruses in vitro by binding of antibody to the surface of the virion. Eight monoclonal antibodies which were directed against at least four non-overlapping antigenic regions of the haemagglutinin protein of A/Aichi/68 virus were tested for inhibitory effect. One of the antibodies directed against the B antigenic site, 22/1, inhibited transcriptase activity, while the other seven antibodies did not. Antibody from a hyperimmune rabbit serum to A/Udorn/72 (H3N2) virions inhibited the transcriptase activity of A/Udorn/72 and A/Aichi/68 (H3N2) viruses but not that of A/WSN/33 (H1N1). The antibody did not cause irreversible inactivation of the transcriptase since full activity was recovered by isolating ribonucleoprotein (RNP) cores from the inhibited virions using NP-40 treatment and subsequent centrifugation in a caesium sulphate density gradient. The antibody did not inhibit transcriptase activity of isolated RNP cores. The virion transcriptase activity was not inhibited by addition of the antiserum after the detergent treatment which is necessary for the activation of the transcriptase activity in vitro. These results suggest that the antibody blocks the activation process of the transcriptase by detergent treatment.

Antibodies, Viral↗
PubMed1985

Dynamic analysis of changing features of tumor cells incubated with antitumor agents in vitro and its application for predictive activity assay of antitumor agents.

Continuous observation of living malignant cells (L1210) in a specially devised glass observation chamber with an inverted microscope made it possible to classify various cellular morphological features induced by antitumor agents into the following four stages: 1) an initial stage consisting of cytoplasmic granulation and coloring, 2) an intermediate stage of shrinkage of nuclei, increases of vacuoles and cytoplasmic budding, 3) a determinate stage of cell ballooning and 4) the terminal stage (cell ghost). Both the initial and intermediate stages are characterized by cellular changes that appear at an early phase and remain opportunistic in terms of viability. Emergence of these cellular changes is largely dependent on the specific mode of action of antitumor agents. In contrast, definite irreversibility in the changes found in both the terminal and determinate stages was confirmed by continuous observation until the cells showed lytic or ghost features, using a video-recording system. A plot of the number of cells counted in both the determinate and terminal stages versus the time-dose schedule is designated as the "time-dose-response" plot, and this proved useful for estimating the characteristics of the antitumor agents tested and the actions of new antitumor agents on malignant cells (predictive activity assay graph).

Animals↗
PubMed1985

Treatment of multiple myeloma with recombinant human leukocyte A interferon.

A phase II study of recombinant human leukocyte A interferon was conducted in 64 patients with multiple myeloma in a multi-institutional cooperative trial. Partial remission was achieved in ten (21.3%) of 47 evaluable patients and minor response was observed in five (10.6%). Side effects were noted in more than two-thirds of the patients. They included fever (58%), malaise (20%), anorexia (52%), nausea and vomiting (26%), lethargy (2%), and myelosuppression (56%). An antibody to recombinant human leukocyte A interferon was detected in one of 20 patients.

Adult↗
PubMed1984

Adenovirus DNA synthesized in the presence of aphidicolin.

Adenovirus types 2 and 5 DNA synthesized in vivo and in vitro in the presence of aphidicolin were studied. Inhibition of adenoviral DNA synthesis by aphidicolin was only 70% even at a concentration of 30 micrograms/ml of aphidicolin, at which the cellular DNA synthesis was completely inhibited. When initiation of the viral DNA synthesis was synchronized with hydroxyurea and labeled with [3H]thymidine for 60 min, the viral DNA synthesized in the presence of 30 micrograms/ml of aphidicolin was not of full length (35 kb) but small (approximately 12 kb) by analysis of alkaline sucrose density gradient centrifugation. When initiation of the viral DNA synthesis was not synchronized, the viral DNAs ranging from full size to 12 kb were synthesized in the presence of aphidicolin, indicating that the nascent DNAs longer than about 12 kb can continue to elongate in the presence of aphidicolin. This 12 kb DNA was not derived from the degradation products of newly synthesized full size adenoviral DNA. The viral DNA synthesis was restored and the full size of adenoviral DNA was attained within 15 min following removal of aphidicolin. About 20% of the entire viral genome length from the 5'-end was not inhibited by aphidicolin, while the synthesis of interior fragments of the adenoviral DNA was markedly inhibited by aphidicolin, judging from the electrophoretic pattern on neutral agarose gel after digestion of DNA with Hind III. These results indicate that aphidicolin inhibits adenoviral DNA replication at the internal region located approximately 20-30% from both terminals.

Adenoviruses, Human↗
PubMed1984

[Direct antitumor activity of biological response modifiers (B.R.M.) proven by an in vitro sensitivity test].

Although the role of biological response modifiers in cancer therapy is well recognised, their mechanism of action remains unsettled. It is empirically considered that there may be some direct antitumor effects induced by some BRM. To analyse the mechanism of action, we evaluated the effects of BRM by using our in vitro sensitivity test, the principle of which was based on dynamic and morphological observation of target cells in vitro. Five kinds of BRM (OK-432, PSK, N-CWS, Bestatin, Lentinan) were tested and the target cell lines were L1210 and P388. The results showed that OK-432 and PSK were mildly cytotoxic, and that OK-432, PSK and Bestatin were effective for cell growth suppression.

Animals↗
PubMed1984

[Effects of single administration of tetrahydropyranyladriamycin (THP) in lymphoid malignancy].

Of 3 patients with adult ALL and 23 patients with NHL treated with intravenous administration of 10 mg/M2 of THP for 5 consecutive days, complete remission was observed in 3 patients and partial remission in 14. The antitumor spectrum of THP seemed to be similar to that of Adriamycin from evidence that THP was effective in patients with NHL of diffuse large and mixed cell type. Neither cardiotoxicity nor alopecia was noticed. Anorexia, nausea or vomiting was mild but granulocytopenia and thrombocytopenia were severe in the patients with ALL and leukemic type NHL. Further studies are required for determining cross resistance to other anthracyclines and an optimal dose schedule.

Adult↗
PubMed1984

[Combination chemotherapy of N(4)-behenoyl-1-beta-arabinofuranosylcytosine, aclarubicin, 6-MP, and prednisolone (BH-AC. AMP therapy) for adult acute non-lymphocytic leukemia].

Sixteen of 20 patients(80%) with adult ANLL treated with B H-AC X AMP therapy attained complete remission (CR). According to the FAB classification, CR rate was 6 out of 8 (75%) for M1, 3 out of 5 (60%) for M2, 2 out of 2 (100%) for M3, and 5 out of 5 (100%) for M4. The median of remission duration in 16 patients who attained CR was 8 months and appeared to be longer in patients with M2, rather than other types, of leukemia than in those with the other types of leukemia. BH-AC X AMP therapy is highly effective for remission induction in adult ANLL and long term disease free survival could be expected by addition of appropriate maintenance therapy.

Aclarubicin↗
PubMed1984

[Antitumor activity of a new nitrosourea, MCNU, on a cellular morphological basis evaluated by a new in vitro antitumor sensitivity assay].

Using our new in vitro antitumor sensitivity assay, the basis of which depends on predictive analysis of morphological findings of L1210 leukemia cells under the influence of antitumor agents, 5 kinds of nitrosoureas including MCNU were comparatively tested for antitumor activity. A cell killing effect became apparent very soon under BCNU and CCNU, rather late under Methyl-CCNU and MCNU, and intermediately under ACNU. Various cellular biological effects were apparently induced in L1210 cells by MCNU and its mechanism of action seemed to be broader than that of any other members of the nitrosoureas.

Animals↗
PubMed1983

Specific inhibitors of eukaryotic DNA synthesis and DNA polymerase alpha, 3-deoxyaphidicolin and aphidicolin-17-monoacetate.

Of several phytotoxins isolated from culture filtrates of Phoma betae Frank PS-13, an incitant of leaf spot disease of sugar beet, three have been identified as aphidicolin, 3-deoxyaphidicolin and aphidicolin-17-monoacetate. Aphidicolin is a selective inhibitor of eukaryotic DNA polymerase alpha (Ikegami et al. (1978) Nature 275, 458-460). Consequently, we studied the action mechanism of 3-deoxyaphidicolin and aphidicolin-17-monoacetate. These aphidicolin analogues markedly inhibited the in vivo DNA synthesis of sea urchin embryos and HeLa cells but not RNA and protein syntheses. Only DNA polymerase alpha, not DNA polymerase beta and gamma, was inhibited by these drugs. The mode of action of these analogues on DNA polymerase alpha from the sea urchin was competitive inhibition with respect to dCTP with Ki values of 0.44 micrograms/ml for deoxyaphidicolin and 0.89 micrograms/ml for aphidicolin monoacetate, respectively. None of the other three dNTPs competed with these drugs. A similar inhibitory mode was observed using the enzyme from HeLa cells and toad oocytes. These drugs at a concentration of 2 micrograms/ml caused a delay in the cleavage of fertilized eggs of the sea urchin and decomposition before blastulation, indicating the possibility of achromosomal cleavage because of the absence of DNA synthesis. Based on the above, it is concluded that these analogues can be used as other inhibitors of eukaryotic DNA synthesis and DNA polymerase alpha.

Animals↗