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Biomedical subjects

M Gamoh

Publications and source records attributed to M Gamoh.

10 recordsLinked to original sources
PubMed2001

Interaction of edrophonium with muscarinic acetylcholine M2 and M3 receptors.

BACKGROUND: It has been reported that edrophonium can antagonize the negative chronotropic effect of carbachol. This study was undertaken to evaluate in detail the interaction of edrophonium with muscarinic Mz and M3 receptors. METHODS: A functional study was conducted to evaluate the effects of edrophonium on the concentration-response curves for the negative chronotropic effect and the bronchoconstricting effect of carbachol in spontaneously beating right atria and tracheas of guinea pigs. An electrophysiologic study was conducted to compare the effects of edrophonium on carbachol-, guanosine triphosphate (GTP)gama S-, and adenosine-induced outward K+ currents in guinea pig atrial cells by whole cell voltage clamp technique. A radioligand binding study was conducted to examine the effects of edrophonium on specific [3HIN-methylscopolamine (NMS) binding to guinea pig atrial (M2) and submandibular gland (M3) membrane preparations, and on atropine-induced dissociation of [3H]NMS. RESULTS: Edrophonium shifted rightward the concentration-response curves for the negative chronotropic and bronchoconstricting effects of carbachol in a competitive manner. The pA2 values for cardiac and tracheal muscarinic receptors were 4.61 and 4.03, respectively. Edrophonium abolished the carbachol-induced outward current without affecting the GTPgamma S- and adenosine-induced currents in the atrial cells. Edrophonium inhibited [3H]NMS binding to M2 and M3 receptors in a concentration-dependent manner. The pseudo-Hill coefficient values and apparent dissociation constants of edrophonium for M2 and M3 receptors were 1.02 and 1.07 and 21 and 34 microM, respectively. Edrophonium also changed dissociation constant values of [3H]NMS without affecting its maximum binding capacities. CONCLUSION: Edrophonium binds to muscarinic M2 and M3 receptors nonselectively, and acts as a competitive antagonist.

Animals↗
PubMed1999

A new combination chemotherapy with cis-diammine-glycolatoplatinum (Nedaplatin) and 5-fluorouracil for advanced esophageal cancers.

OBJECTIVE: The efficacy of a new chemotherapeutic combination consisting of Cis-diammineglycolatoplatinum (Nedaplatin), a derivative of cisplatin (CDDP), and 5-fluorouracil (5FU) was evaluated in patients with advanced esophageal carcinomas. METHODS: Nedaplatin was administered at a dose of 80 or 100 mg/m2 with 500 ml of saline by slow drip infusion for 120 minutes on day 1. 5FU at a dose of 350 or 500 mg/m2 was mixed with 1,000 ml of saline and administered by continuous infusion for 24 hours on days 1 to 5. PATIENTS OR MATERIALS: This combination chemotherapy was tried in 17 patients with metastatic, recurrent, or bulky unresectable esophageal cancers. Of these, 15 evaluable patients received at least two courses of chemotherapy. RESULTS: The response rates in assessable and all patients were 60% and 52.9%, respectively. Cases with lymph node and liver metastases, as well as primary lesions, showed excellent response to the therapy with positive response rates of 54.5% (6/11), 100% (5/5) and 58.4% (7/12), respectively. The median response duration was 7 (range 3 to 37+) months for patients who achieved a partial response. Adverse drug reactions were limited to three cases of grade 3 toxicity, including allergy, and decreased hemoglobin and platelets, which were well tolerated by the patients. CONCLUSION: The present study thus indicated the combination chemotherapy of Nedaplatin and 5FU to be safe and efficacious for advanced esophageal cancer. Further investigations are clearly warranted.

Aged↗
PubMed1991

Mutations of the P53 gene, including an intronic point mutation, in colorectal tumors.

In this study, analysis of structural changes of the p53 gene in colorectal tumors revealed point mutations detected in 8 of 14 carcinomas and 2 of 2 adenomas. Of these 10 cases with point mutations, eight had one or more missense mutations, one had a nonsense mutation, and the remaining one had, interestingly, an intronic point mutation with subsequent activation of a cryptic splice donor site in the flanking exon. This report contains the first identification of an intronic point mutation of the p53 gene in a colorectal cancer case.

Amino Acid Sequence↗
PubMed1990

Evaluation of mizoribine as an immunosuppressant in subrenal capsule assay using immunocompetent mice.

We studied the application of mizoribine (MZR) to normal immunocompetent mice in subrenal capsule assay (SRCA) by means of tumor growth curve determination, histological analysis and autoradiography. At 400 mg/kg, MZR prolonged the actual tumor growth and moderately reduced the host reaction. Doses below 200 mg/kg did not effectively suppress the host reaction. The maximal weight loss of mice in the 400 mg/kg group reached 29%, but did not exceed 10% within 8 days. Hence, we applied 400 mg/kg of MZR to SRCA for up to eight days for cancer chemotherapy testing. This dose of MZR did not affect the labeling index of tumor cells compared with the control.

Animals↗
PubMed1990

[Subrenal capsule assay using nude mice].

Six-day subrenal capsule assay (SRCA) using normal immunocompetent mice developed by Bogden et al. is a promising in vivo chemosensitivity test. This method, however, has a problem of influence of the host reaction. We compared the tumor growth kinetics and host reaction between normal immunocompetent and nude mice. The tumor diameter increased until day 6 in normal and day 16 in nude mice, respectively. However the histological finding revealed many host reactive cells and few viable tumor cells on day 6 in normal mice, and well preserved tumour cells on day 16 in nude mice. These results were supported by flow cytometrical analysis. Then, we examined two immunosuppressive drugs; cyclophosphamide (EX) and cyclosporin A (CSA) in SRCA. The tumors increased in the diameter until day 16 in both EX and CSA-treated groups, but the results of the histological examination showed that tumor cells were preserved in tissue on day 14 in CSA-treated and day 6 in EX-treated group. These results were also supported by flow cytometrical analysis. From the investigation of antitumour activities of adriamycin (ADR) and mitomycin C, it was suggested that the 12-day assay was suitable if nude mice were used in SRCA, and six-day assay also, if EX-treated normal mice were used. In CSA-treated group, more toxicity of anticancer drugs was manifested than usual. We studied whether or not CSA had a usefulness in SRCA with normal immunocompetent mice. Sixty mg/kg of CSA was given to BDF1 mice daily SC, and various dosage of ADR was given i.v. on day 2. The body weight of BDF1 mice decreased over 20% within 10 days when ADR was given at more than 5 mg/kg. MX-1, a human breast carcinoma cell line, is known to be sensitive to ADR. This tumor was implanted SC in the back of BALB/c nu/nu mice and chemosensitivity was tested against ADR. ADR resulted to be positive at the dose of 8 mg/kg. On the other hand, the dose of 5 mg/kg proved to be negative, and hence the result of SRCA would be false negative, if the dose of ADR is reduced to avoid the toxicity of CSA. The tumor grew slowly when only 60 mg/kg of CSA was given daily for three weeks, and the inhibition rate was 56.2%. The toxicity of CSA was neglected because the body weight loss was approximately 13%. CSA may have the antitumor effect by itself, and EX did not suppress the host reaction sufficiently.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1989

[In vivo antitumor activity of mitoxantrone and the flow cytometric analysis of its influence on cell cycle transition--comparison with doxorubicin and aclarubicin on ascitic hepatoma AH109A cells].

Mitoxantrone was compared with doxorubicin and aclarubicin of its in vivo antitumor activity and influence on cell cycle transition by use of rat ascitic hepatoma AH109A. Antitumor activity determined by the cell growth curve was similar in mitoxantrone and doxorubicin, but the sensitivity of AH109A to aclarubicin was lower than that to the other two drugs. Doxorubicin and mitoxantrone showed all phase arrests with 1/10 of maximally tolerated dose (MTD), and with lower concentrations a strong arrest at G2 phase was observed, thus, mitoxantrone appeared to have a similar antitumor activity on AH109A to that of doxorubicin. Aclarubicin, with 1/10 MTD, demonstrated only a transient arrest at G2 phase, cells arrested at G2 phase entering into the next phase. With below 1/10 MTD, there was no appearance on histograms, and the influence on AH109A cell cycle transition by aclarubicin was considered to be little in comparison with doxorubicin and mitoxantrone.

Aclarubicin↗
PubMed1989

[An experimental study on subrenal capsule assay (SRCA)--problems for the use of immunosuppressive agents].

We studied whether or not cyclosporin A (CSA) has a usefulness in subrenal capsule assay (SRCA) with normal immunocompetent mice. Sixty mg/kg of CSA was given to BDF1 mice daily subcutaneously, and various dosages of adriamycin (ADR) was given intravenously on day 2. The body weight of BDF1 mice decreased over 20% within ten days when ADR was given at more than 5 mg/kg. MX-1, a human breast carcinoma line is known to be sensitive to ADR. This tumor was implanted subcutaneously in the back of BALB/c nu/nu mice and chemosensitivity was tested against ADR. ADR resulted to be positive at the dose of 8 mg/kg. On the contrary, the dose of 5 mg/kg proved to be negative, and hence the result of SRCA would be false negative, if the dose of ADR is reduced to avoid the toxicity of CSA. The tumor grew slowly when only 60 mg/kg of CSA was given daily for three weeks, and the inhibition rate was 56.2%. The toxicity of CSA was neglected because of the body weight loss was approximately 13%. CSA may have the antitumor effect by itself, and we therefore suggest that the CSA is not useful for SRCA.

Adenocarcinoma↗
PubMed1988

[An experimental study on SRCA (subrenal capsule assay)--using immunosuppressive maneuvers].

Six-day SRCA using normal mice developed by Bogden et al. is one of the most promising methods for in vivo chemosensitivity tests. However, this method has a problem on the influence of the host reaction during six days. Therefore, we examined the tumour growth kinetics, host reaction and expression of antitumor effect on three immunosuppressive maneuvers; cyclophosphamide (EX), cyclosporin A (CSA), and total body irradiation (TBI). The tumour diameter increased until day 16 in EX and CSA-treated groups and day 10 in TBI-treated group, but the results of the histological examination showed that tumour cells were preserved in tissue on day 14 in CSA-treated group and day 6 in EX and TBI-treated groups. These results were supported by flow cytometrical analysis. The autoradiogram using 3H-TdR showed that labelling index of the tumour cells was not affected by these immunosuppressive maneuvers. From the investigation of the antitumour activity of adriamycin and mitomycin C, it was suggested that the 12-day assay was suitable if nude mice were used in SRCA, and six-day assay, if EX-treated normal mice were used. In CSA-treated group, toxicity of anticancer drugs was manifested than usual.

Adenocarcinoma↗
PubMed1988

[An experimental study on SRCA (subrenal capsule assay)--comparison of the test between normal and nude mice].

Six-day SRCA using normal mice developed by Bogden et al. is a promising in vivo chemosensitivity test. However, this method has a problem on the influence of the host reaction. We compared the tumor growth kinetics and host reaction between normal and nude mice. The tumor diameter increased until day 6 in normal and day 16 in nude mice, but the histological finding revealed many host reactive cells and few viable tumour cells on day 6 in normal mice, and well preserved tumour cells on day 16 in nude mice. These results were supported by flow cytometrical analysis. Autoradiogram using 3H-TdR showed a recovery of labeling index to the steady label by day 1. This index was similar between normal and nude mice. When antitumor activity of adriamycin, cisplatin or mitomycin C was compared with nude mice system, the order of effectiveness was the same as the system using nude mice implanted tumor cells subcutaneously and given the drugs intraperitoneally, but different in normal mice.

Adenocarcinoma↗