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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 1,045 records · Page 58Linked to original sources

[Studies of the propriety of the items adopted for the special health examination of vibration hazards at present (author's transl)].

Skin temperature, vibratory sense, nail press test and pain sense are customarily used as the items in the special health examination for finding vibration hazards at present. These items are measured under the condition of room temperature at 20 to 23 degrees c and after 10-minute immersion in cold water at 5 degrees C or 10 degrees C. In this report, the propriety of these items was investigated on the basis of measurements in 274 healthy chain saw operators and 294 healthy bush cutter operators. The 10-minute immersion test in cold water at 10 degrees C was adopted in this experiment. The results obtained are as follows: Skin temperatures of the chain saw and bush cutter operators did not show any significant difference by age under the condition at the room temperature, but the recovery in the subjects in the twenties was faster than in the other. Skin temperatures at the 10th minute after the 10-minute immersion test in cold water at 10 degrees C showed very wide deviations among the subjects. Vibratory senses of the aged subjects markedly lowered in comparison with those of the younger subjects. Recovery of vibratory sense after the immersion in cold water showed a tendency which is faster than that of the skin temperature. Correlation between the skin temperature and the vibratory sense at the 10th minute after the immersion was statistically significant. Most of the subjects showed the recovery time within 2 sec with the nail press test under the condition of the room temperature and at the 10th minute after the immersion. Above 95% of subjects complained pain sense with one gram weight at the measurement under the all conditions except immediately after the 10-minute immersion test. From the above results, it should be considered that the value of these measurement may be dominated by the age of the subjects and that the immersion test in cold water to the tests of vibratory sense and pain sense may not have important role in the diagnosis of vibration hazards.

Adult↗

Potentiation of therapeutic effects of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride by 6-thioguanine in mouse tumor systems: comparison with other antimetabolites.

Antitumor activities of a combination chemotherapy with a water-soluble nitrosourea, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), and a single dose of 6-thioguanine were studied using three obstinate murine tumor systems, i.e., Lewis lung carcinoma, B16 melanoma, and an advanced stage of L1210 leukemia systems. Therapeutically synergistic effect was observed either definitely against 1- or 2-day-old Lewis lung carcinoma and 6-day-old L1210 leukemia or moderately against 1-day-old B16 melanoma. Single intravenous treatment on day 7 after subcutaneous implantation of Lewis lung carcinoma, when the tumors had already metastasized to the lungs, produced a significant regression of tumor and a significant increment in survival time of tumor-bearing mice. In comparative studies, the combination of ACNU and 6-thioguanine showed a greater and a wider spectrum of antitumor activities against these tumors than those obtained by the combination with ACNU and a single dose of 5-fluorouracil, methotrexate, or 6-mercaptopurine. Increment in lethal toxicity for normal and tumor-bearing mice was not observed by the combination of ACNU and 6-thioguanine in contrast to definite increases in this toxicity by the combination of ACNU and 5-fluorouracil. The present experimental results may suggest the clinical utility of the combination chemotherapy with ACNU and 6-thioguanine in the treatment of several solid tumors as well as acute leukemias.

Animals↗

Therapeutic synergism elicited by the combination of 6-thioguanine and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride: synergistic cytocidal activity against L1210 cells in vitro.

In order to clarify the mechanism of therapeutic synergism elicited by a combination of 6-thioguanine and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), the cytocidal activity towards L1210 leukemic cells in vitro of these two drugs, alone and in combination, was examined by the soft agar cloning assay and the regrowth assay methods. More than 10-fold greater cell-killing activity than the expected additive survival (the product of fractional survival obtained for each drug alone) was observed on treatment with the combination of these drugs in both assay methods. More-over, dose- and treatment schedule-dependent antitumor activity of this combination treatment against L1210 leukemia in vivo was clearly reflected in the cytocidal activity towards L1210 cells in vitro. These findings suggest that the therapeutic synergism elicited by the combination of ACNU and 6-thioguanine results from synergistic cytocidal activity towards tumor cells.

Animals↗

Lethal toxicity and myelotoxicity to mice of the combination of 6-thioguanine and 3-[(4-amine-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride.

In order to determine the mechanism of therapeutic synergism elicited by a combination of 6-thioguanine and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU) against various murine tumors, side effects of host animals due to the combination of these two drugs were examined. The combination toxicity index of these drugs given simultaneously was determined to be 1.5, i.e., this indicates that the combination of ACNU and 6-thioguanine is less-than-additive with respect to the lethal toxicity. More-over, this combination treatment appeared to be at least no more than additive with respect to bone marrow toxicities as judged on the basis of bone marrow cellularity and peripheral white blood cell counts. In addition, the effects of treatment schedules, which were clearly observed in the therapeutic effect, on the side effects due to this combination treatment were also examined. However, no specific decrease or increase in side effects on host animals on this specific treatment schedule or the other treatment schedule was seen.

Animals↗

Tritiated thymidine autoradiographic study on origin and renewal of gastrin cells in antral area of hamsters.

The origin and renewal of the gastrin cells in the pyloric glands of hamsters were studied by [3H]thymidine autoradiography combined with the immunoperoxidase identification technique. After a single injection of [3H]thymidine, the labeling index of gastrin cells was 0.3%, indicating that a few gastrin cells at the isthmus region have a self-replicating activity. Following pulse labeling after five repeated injections of [3H]thymidine at 6-hr intervals, the labeling index of the gastrin cells showed a linear increase (from 1.2% on the 1st day to 5.2% on the 4th day), and attained a plateau (5.6%) on the 5th day. These findings indicate that most gastrin cells differentiate functionally within 5 days. On the 5th day after the last of 41 injections repeated at 6-hr intervals, the labeling index of gastrin cells was 25.8%, and it decreased gradually as follows: 22.3%, 18.3%, 11.2%, 7.3%, 0.9%, and 0% on the 10th, 15th, 20th, 30th, 50th, and 100th day, respectively. From analysis of this decreasing curve, the turnover time of the gastrin cells (a half-life of the cells) was estimated to be 10-15 days. Spatially. the labeled gastrin cells were at first found in a region from the isthmus to the upper level of the glands and later in the lower level of the glands. This indicates that the gastrin cells arising from immature precursor cells at the isthmus region migrate downwards toward the bottom of the glands.

Animals↗

Comparison of antitumor activities of nitrosourea derivatives against mammary breast carcinoma (MX-1) in nude mice.

A study was conducted to evaluate the antitumor activities of six nitrosourea derivatives against the xenograft of mammary breast carcinoma transplanted in nude mice (MX-1). The drugs employed in this study were 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), 1-(2-chloroethyl)-3-(methyl alpha-D-glucopyranos-6-yl)-1-nitrosourea (MCNU), 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Me-CCNU), and 2-[3-(2-chloroethyl)-3-nitrosoureido]-2-deoxyl-D-glucopyranose (DCNU, chlorozotocin). CCNU and Me-CCNU were administered intraperitoneally, and the other were given intravenously through a tail vein. Antitumor activities were assessed in terms of the drug-induced tumor growth inhibition based on caliper measurements. A single treatment with ACNU (40 mg/kg) induced 92% tumor regression, compared to 73% and 69% tumor regression induced by MCNU (15 mg/kg) and CCNU (50 mg/kg), respectively. GANU and DCNU were less effective. To evaluate the antitumor activity of the drugs, we employed the predetermined dose lethal to one-tenth of BDF1 mice (LD10) for each drug as a standard therapeutic dose to nude mice; doses higher than LD10 and one-half and/or one-fourth of LD10 were also given. The results suggest that LD10 in BDF1 mice could be employed as a standard therapeutic dose in the chemotherapy of nude mice.

Animals↗

In vitro sensitivity test of stomach cancer tissues by the use of metal grid method.

Ninety-nine specimens obtained from 53 patients with stomach cancer were cultured for about 3 days by means of the stainless steel grid method. In vitro effects of antitumor drugs on the cancer cells were evaluated autoradiographically or biochemically using a liquid scintillation counter to measure the uptake of 3H-thymidine. The radioactivity of the labeled tumor cells of both control fragments and fragments affected by drugs varied greatly among individual tumors. Therefore, the in vitro efficacy of antitumor drugs was represented as a comparison with that of control fragments. Positive correlation between in vitro tests and the clinical effects of antitumor drugs was observed in the specimens of 18 cases.

Antineoplastic Agents↗

Clinical value of immunochemotherapy with OK-432 or PS-K for stomach cancer patients.

A prospective clinical trial was undertaken in 121 patients with stomach cancer to compare immunochemotherapy with 5-fluorouracil and FT-207 combined with OK-432 or PS-K, immunostimulators, and plain chemotherapy with 5-fluororacil and FT-207. Of the 121 patients who received immunochemotherapy, 67 patients (group A) had undergone curative removal of the tumor. The other 54 patients had undergone noncurative tumor removal or had recurrence after non-curative tumor removal and they were divided into two groups (groups B and C) on the basis of lymphocyte reactivity induced with PHA. Although group A exhibited a significant increase in PHA-induced lymphocyte transformation and a trifling increase in lymphocyte counts, its survival rate within a 36 month period did not differ from that of the peer controls. Group B, composed of 21 patients showing improvement of PHA-induced lymphocyte transformation, significantly prolonged its survival compared to the peer controls. The survival of group C, composed of 33 patients showing a gradual drop in PHA-induced lymphocyte transformation, was not prolonged compared to the peer control patients; and they showed significant decreases in lymphocyte counts. The overall survival of group B and group C was not superior to that of the 48 peer controls.

Adult↗

Carcinoembryonic antigen (CEA) in gastric juice or feces as an aid in the diagnosis of gastrointestinal cancer.

Carcinoembryonic antigen (CEA) levels in the feces and serum were evaluated in 22 colorectal cancer patients and 20 healthy volunteers; in CEA levels gastric juice and serum were also evaluated in 28 gastric cancer patients and 14 peptic ulcer patients. Fecal CEA was found in all of 22 colorectal cancer patients as well as in the 20 healthy volunteers. Elevated fecal CEA levels were observed in the colorectal cancer patients, as compared to the healthy volunteers. The feces of 15 of the 22 colorectal cancer patients contained CEA at concentrations higher than the mean value plus twice the standard deviation of the healthy volunteers. The fecal CEA levels did not correlate directly either with Dukes' stage or serum CEA levels. CEA in gastric juice was elevated significantly in 26 of gastric cancer patients, with the exception of two patients with early gastric cancer. On the other hand, serum CEA was elevated in only nine of the 28 gastric cancer patients. These results point out the distinct value of assaying CEA in the feces or gastric juice as an aid in the diagnosis of colorectal or gastric cancer.

Adult↗