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Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 433 records · Page 24Linked to original sources
PubMed1987

Ionic mechanism of the outward current induced by intracellular injection of inositol trisphosphate into Aplysia neurons.

Inositol 1,4,5-trisphosphate (InsP3) has been proposed to be the intracellular second messenger in the mobilization of Ca2+ from intracellular stores in a variety of cell types. The ionic mechanism of the effect of intracellularly injected InsP3 on the membrane of identified neurons (R9-R12) of Aplysia kurodai was investigated with conventional voltage-clamp, pressure-injection, and ion-substitution techniques. Brief pressure injection of InsP3 into a neuron voltage-clamped at -40 mV reproducibly induced an outward current (10-60 sec in duration, 20-60 nA in amplitude) associated with a conductance increase. The current was increased by depolarization and decreased by hyperpolarization up to -80 mV, where it disappeared. Extracellular application of tetraethylammonium (TEA; 5 mM) blocked the InsP3-induced outward current, and the current was not affected by the presence of bath-applied 4-aminopyridine (4-AP; 5 mM). The InsP3-induced outward current recorded at a holding potential of -40 mV increased in amplitude in low-K+ solutions and decreased in amplitude in high-K+ solutions. Alteration of [Cl-]0, as well as perfusion with Ca2+ free plus 2 mM EGTA solution, did not affect the outward current. The InsP3-induced outward current was found to disappear when the neuron was injected with the Ca2+ chelator EGTA. The outward current evoked by repeated InsP3 injection at low doses exhibited summation and facilitation and, at high doses, was shown to desensitize. The calmodulin inhibitor N-(6-amino-hexyl)-5-chloro-1-naphthalene sulfonamide (W-7; 20-50 microM), inhibited both the InsP3-induced and the Ca2+-activated outward currents. An intracellular pressure injection of Ca2+ ions into the same identified neuron was shown to produce an outward current associated with a K+ conductance increase similar to the InsP3-induced current, and the current was blocked by bath-applied TEA (5mM). These results suggest that brief pressure injection of InsP3 into certain identified neurons of Aplysia induces a 4-AP-resistant, TEA-sensitive K+ current activated by increased intracellular free Ca2+ concentration, and this increase might be the result of the mobilization of Ca2+ from intracellular stores by InsP3.

4-Aminopyridine↗
PubMed1987

A factor inducing differentiation of the human monocytic cell line U-937 produced by 12-O-tetradecanoylphorbol 13-acetate-treated U-937.

A new factor capable of inducing differentiation of human leukemic cell line U-937 into macrophages was found and partially purified from the conditioned medium of U-937 previously treated with 12-O-tetradecanoylphorbol 13-acetate. The purification procedure included ultrafiltration, DEAE-Sephacel and butyl-Toyopearl column chromatography. The purified factor gave a major band of protein with a molecular weight of 67,000 daltons which coincided with the biological activity of differentiation-inducing factor, and it was not adsorbed on a concanavalin A column. These results suggest that this factor is distinct from other differentiation-inducing factors.

Cell Differentiation↗
PubMed1987

[Cisplatin, adriamycin and cyclophosphamide combination chemotherapy of epithelial ovarian cancer].

The chemotherapeutic effects of cisplatin + adriamycin + cyclophosphamide (PAC) on 50 epithelial ovarian cancers were compared with the effects of 5-fluorouracil + cyclophosphamide + mitomycin C (FAM) in 17 patients. The cumulative survival at 5 years was 61.1% in all patients, 62.5% in patients treated with PAC and 54.7% in patients treated with FAM. The 5-year survival rate was 100% in Stage I, 63.5% in Stage II, 40.1% in Stage III and 22.2% in Stage IV. Of 22 patients with Stage III and IV treated with PAC, 16 patients responded (8CRs + 8PRs). The median survival duration of the treated patients was 19 months. On the other hand, of 8 patients treated with FAM, only one patient responded (PR). The median survival duration was 7 months. These results indicated the effectiveness of PAC chemotherapy against advanced ovarian cancer. No severe toxicity was observed during treatment with PAC or FAM.

Adolescent↗
PubMed1987

[Assessment of the establishing individual protocol for effective chemotherapy of ovarian cancer--fundamental research using human tumor-nude mouse system].

Experimental chemotherapy was performed using the human tumor-nude mouse system. The tumors were mucinous cystadenocarcinoma (OVA-1), undifferentiated carcinoma (OVA-2), endometrioid adenocarcinoma (OVA-3), serous cystadenocarcinoma (OVA-4) and three yolk sac tumors (YST-1, -2, -3). The drugs tested were adriamycin, bleomycin, cisplatin, cyclophosphamide, 5-fluorouracil, ifosfamide, mitomycin C, vinblastine, etoposide and teniposide. The dosages employed here were about one-third and one-ninth of the LD50 used for conventional mice. The results obtained were as follows: 1 A clear correlation between the antitumor activity of the drug and the histological type of the tumor was observed. The results indicated the importance of making a chemotherapeutic protocol according to the histological type of the individual tumor. 2 The antitumor activity depended on the dosage of the drug. The results suggested that it was necessary to increase the dosage of the anticancer drugs to obtain further clinical effects on patients with ovarian cancer. 3 The administration of a single drug in a sufficient dosage produced more effective antitumor activity rather than multidrug treatment. The results suggested that combination chemotherapy might not necessarily be the best way to effectively treat patients with ovarian cancer.

Adenocarcinoma↗
PubMed1987

[Clinical studies of norfloxacin on respiratory tract infections in aged people].

Norfloxacin (NFLX), an oral antibacterial agent of new quinolone derivative, was administered at daily doses of 300-600 mg t.i.d. to 20 aged patients with respiratory tract infections. The results obtained are summarized as follows. 1. Clinical efficacies were moderate in 6 patients with upper respiratory tract infections, and moderate in 11 patients and fair in 3 patients with lower respiratory tract infections. In the 20 patients, overall clinical efficacies were moderate in 17 patients, hence the efficacy rate was 85%. 2. Bacteriologically, causative organisms were detected in 10 of the 14 cases with lower respiratory tract infections. In these cases, bacteriological responses were "eradicated" in 9 cases, "decreased" in 1 case and "unknown" in 1 case, the rate of eradication was 90%. 3. No adverse reactions or abnormal laboratory test values were observed.

Aged↗
PubMed1987

[Antitumor activity of platinum analogs against human ovarian tumors heterotransplanted into nude mice].

The chemotherapeutic effects of CDDP, CBDCA and CHIP on human ovarian cancers heterotransplanted into nude mice (mucinous cystadenocarcinoma OVA-1, poorly differentiated adenocarcinoma OVA-2, endometrioid adenocarcinoma OVA-3, serous cystadenocarcinoma OVA-4, and three yolk sac tumors YST-1, YST-2, YST-3) were examined. OVA-1 did not respond to CDDP, although it responded well to CBDCA and CHIP. OVA-2 responded well to all these platinum analogs. OVA-3 responded well to CDDP, but did not respond to CBDCA or CHIP. OVA-4 responded well to CDDP and CBDCA, but did not respond to CHIP. Tumors YST-2 and YST-3 exhibited broadly comparable sensitivity to CDDP and the two other analogs, and YST-1 was substantially more sensitive to CDDP than to CBDCA or CHIP. The results indicated the necessity of selection of platinum analogs according to the histological types of tumor for the effective treatment of ovarian cancer.

Animals↗
PubMed1987

Cyclosporin A stimulates hair growth in nude mice.

When cyclosporin A (CyA) at doses of 10 and 100 mg/kg body weight/day was given for 14 days to six-week-old female and male nude mice, the length of the hair of CyA-treated mice began to increase from day 7 of the treatment at both doses. There was no hair growth in the control mice, which were given only olive oil. The hair length of CyA-treated mice was 3 to 4 times longer than that of control mice. CyA at both doses induced hair growth to the same extent. There was no difference in the hair growth between the male and female mice. The growth of hair was apparent on the neck, back, and hip. However, no hair growth was observed in the abdominal region. The hair length of the CyA-treated mice decreased after cessation of the treatment, and returned to the level of the control mice on day 14 after the end of the treatment. Microscopic examination revealed that there was no difference in the number of hair follicles between the control and the CyA treated mice.

Animals↗
PubMed1987

[Antitumor effects of high-dose cisplatin in hypertonic saline against human ovarian tumors heterotransplanted in nude mice].

To overcome the dose limiting toxicity of cisplatin we administered high-dose (12 mg/kg) cisplatin together with hypertonic (3%) saline to tumor-bearing nude mice three times at four day intervals. The heterotransplanted human ovarian tumors consisted of a mucinous cystadenocarcinoma (designated as OVA-1), a poorly differentiated adenocarcinoma (OVA-2), an endometrioid adenocarcinoma (OVA-3) and three yolk sac tumors (YST-1,-2,-3). The mean volumes of the tumors in animals treated with a standard dose 6 mg/kg of cisplatin in 0.9% NaCl or 12 mg/kg of cisplatin in 3% NaCl were, as a percentage of the mean tumor volume in untreated animals: 51 and 26 for OVA-1, 28 and 15 for OVA-2, 11 and 7 for OVA-3, 7 and 14 for YST-1, 3 and 12 for YST-2, and 11 and 10 for YST-3, respectively. The most interesting result was that a high dose (12 mg/kg) of cisplatin succeeded in producing a strong antitumor effect on mucinous cystadenocarcinoma (OVA-1), which was resistant to standard dose cisplatin (6 mg/kg). A comparison of the body weight of tumor-bearing nude mice before and on Day 30 of treatment did not show any appreciable treatment-related changes.

Adenocarcinoma↗
PubMed1987

[Effect of post operative maintenance chemotherapy against ovarian cancer].

The significance of maintenance chemotherapy after surgery for ovarian cancer was examined using a human tumor-nude mouse system. Experiment 1: The human yolk sac tumor of the ovary (YST-2) heterotransplanted into nude mice was used. The tumor-bearing mice were administered 100 mg/kg of 1-Hexylcarbamoyl-5-fluorouracil (HCFU) orally for 60 days after tumor resection. Control mice were given 0.1 ml 0.3% methylcellulose after tumor resection. When the tumor was completely resected by surgery, HCFU treatment succeeded in decreasing the recurrence rate of the tumor, and in improving the survival rate of the host mice. However, when the macroscopic tumor was left in the host mouse, HCFU treatment did not affect either the recurrence rate of the tumor or the survival rate. Experiment 2: The human poorly differentiated adenocarcinoma of the ovary (OVA-2) heterotransplanted into nude mice was used. Administration of 100 mg/kg of HCFU immediately after the heterotransplantation into nude mice for 60 days suppressed the tumor growth. HCFU treatment improved the survival rate of the tumor-bearing mice. The antitumor effect of HCFU on the OVA-2 tumor was confirmed by histological examination. These experiments revealed that the maintenance chemotherapy after surgery for ovarian cancer was important in the effective treatment of the patient (tumor-bearing host).

Animals↗
PubMed1987

[Ifosfamide, cisplatin, adriamycin combination chemotherapy in gynecologic cancer].

Thirteen patients with gynecologic cancer were treated with ifosfamide (2 g X 5), cisplatin (70 mg/m2) and adriamycin (20 mg/m2) combination chemotherapy. The response rate of 7 evaluable patients was 43%, with a median duration of survival of 14 months. Six patients with non-measurable disease are currently free from disease with a median duration of survival of 18 months. This combination caused reversible myelosuppression. No hemorrhagic cystitis was observed.

Adult↗
PubMed1986

Enzyme immunoassay for captopril.

A simple enzyme immunoassay for the determination of captopril was developed. A specific antibody for captopril was produced in rabbits that were immunized with a hapten-bovine immunoglobulin G conjugate, which was prepared by using 4-(maleimidomethyl)cyclohexane carboxylic acid as a spacer group. The limit of detection in plasma is 0.5 ng/mL. The assay has an adequate specificity, so isolation of captopril is unnecessary.

Animals↗
PubMed1986

A sensitive assay of GTP cyclohydrolase I activity in rat and human tissues using radioimmunoassay of neopterin.

A highly sensitive and simple assay for the activity of GTP cyclohydrolase I (EC 3.5.4.16) was established using a newly developed radioimmunoassay. D-erythro-7,8-Dihydroneopterin triphosphate formed from GTP by GTP cyclohydrolase I was oxidized by iodine and dephosphorylated by alkaline phosphatase to D-erythro-neopterin, and quantified by a radioimmunoassay for D-erythro-neopterin. This method was highly sensitive and required only 0.2 mg of rat liver tissues for the measurement of the activity. It was reproducible and can be applied for the simultaneous assay of many samples. The activity of GTP cyclohydrolase I was measured in several rat tissues. For example, the enzyme activity in rat striatum (n = 5) was 13.7 +/- 1.5 pmol/mg protein per hour (mean +/- SE), and agreed well with those obtained by high-performance liquid chromatography with fluorescence detection. The activity in the autopsy human brains (caudate nucleus) was measured by this new method for the first time. The activity in the caudate nucleus from parkinsonian patients (n = 6) was 0.82 +/- 0.56 pmol/mg protein per hour which was significantly lower than the control value, 4.22 +/- 0.43 pmol/mg protein per hour (n = 10).

Aminohydrolases↗