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Biomedical subjects

K Enomoto

Publications and source records attributed to K Enomoto.

At least 289 records · Page 16Linked to original sources

Nasal responsiveness to methacholine stimulation in allergic rhinitis patients.

We examined the nasal responsiveness to topical methacholine application in allergic rhinitis and non-allergic chronic rhinitis patients, and in control subjects. Methacholine responsiveness was significantly higher in allergic rhinitis patients than in non-allergic patients and control subjects. In perennial rhinitis, methacholine responsiveness correlated with the severity of daily nasal symptoms and those provoked by specific allergen challenge tests. Among nasal symptoms, hyper-rhinorrhoea was found to be closely related to methacholine responsiveness. As a result of these findings, the possibility of cholinergic hyper-reactivity in allergic rhinitis patients is discussed.

Administration, Topical↗

Combined cytotoxic and endocrine therapy for human breast carcinoma (Br-10) serially transplanted into nude mice.

Cytotoxic and endocrine therapy on a human breast carcinoma (Br-10) serially transplanted into nude mice was given with reference to the sequence of drug administration. Mitomycin C (MMC) was combined with 2.5 mg/kg of tamoxifen (TAM). MMC was dissolved in 0.2 ml of physiological saline and administered intraperitoneally once weekly. TAM was dissolved in 0.1 ml of sesame oil and administered intramuscularly twice weekly. Both drugs were administered in the reverse sequence for 2 or 3 weeks. Cytosol estrogen receptor (ERc), nuclear estrogen receptor (ERn) and progesterone receptor (PgR), and 3H-thymidine uptake labeling index (L.I.) were assayed after the treatment. When 1.5 mg/kg of MMC was combined with TAM, statistically significant differences were nil between the different sequential administrations. When the MMC administration was reduced to 0.75 mg/kg and 2 weeks, respectively, the MMC----TAM sequence was more effective than the reversed sequential administration. MMC preserved ERc and depressed L.I. to almost half of that of the control tumor. TAM generated the ER systems and slightly depressed L.I. These different modes of action between MMC and TAM on ER systems and L.I. may explain the antitumor effects of different sequential administrations.

Adult↗

Role of IA-positive cells in the beneficial effect of donor blood transfusion and induction of suppressor cells in cardiac allotransplantation of rats.

An attempt was made to reveal the role of Ia-positive cells in the beneficial effect of pretransplant donor-specific blood transfusion (DST) and induction of suppressor cells in the cardiac allotransplantation of rats. Mean graft survival time (MST) of F344 (RT1 1v1) hearts transplanted in WKA (RT1k) rats was 6.5 +/- 0.8 days. Pretreatment of recipients with 1 ml DST 10 days before grafting prolonged it to 56.5 +/- 38.1 days. Plasma or erythrocytes did not prolong MST at all, whereas pretreatment with 1 X 10(7) lymphocytes prolonged MST significantly. B enriched cells separated on a nylon-wool column prolonged MST, but T-enriched cells did not. Treatment of lymphocytes with interspecies crossreactive monoclonal anti-Ia antibody and complement eliminated the ability of lymphocytes to prolong MST, suggesting an important role of Ia-positive cells in the beneficial effect of DST. The role of Ia-positive cells in prolonging graft survival, was analyzed by a cell and serum transfer experiment. MST of F344 heart allografts transplanted in sublethally irradiated (500 rads) WKA rats was 17.4 +/- 4.0 days. MSTs of allografts in rats irradiated and treated with serum or spleen cells of blood-conditioned rats were 23.2 +/- 1.6 (P less than 0.05) and 5.2 +/- 0.7 (NS) days, respectively. On the other hand, MSTs of the grafts in rats irradiated and treated with serum or spleen cells harvested from rats that had accepted grafts for 30 days were 18.7 +/- 1.9 (NS) and 63.8 +/- 29.9 (P less than 0.01) days, respectively. The results indicate that the initial role of a serum factor in prolonging graft survival induced by DST containing Ia-positive cells was followed by activating suppressor cells by the presence of the allograft.

Animals↗

[Controversy on the treatment of early breast cancer].

Ten year survival rate following modified radical mastectomy for breast cancer with stage I was 84 per cent. Sixteen per cent of them had metastases in the axillary lymph nodes. However, setting limits to under 1.0 centimeter in diameter of the tumor, rate of the axillary metastases was 7 per cent. In addition to it, using the X ray mammography and the histological examination of the biopsied specimen, an early breast cancer without metastasis could be selected rather accurately, that is the axillary dissection could be saved for such early breast cancer. On the other hand, it was recognized that intramammary multicenctricity was 96 cases, (8.5%), in 970 breast cancer, residual cancer following the excisional biopsy was 61 cases (32%) in 176 breast cancer, and breast cancer risk following microdochectomy for intraductal papillary lesions was 6.7%. Accordingly, now that a lesion is certified as breast cancer, total mastectomy is required at least.

Breast Neoplasms↗

Human breast carcinoma (MCF-7) serially transplanted into nude mice.

The tumor cells (0.5 ml, 1 X 10(7) of MCF-7 line were inoculated into the subcutaneous tissue or intraperitoneum of female BALB/c nude mice. Primarily transplanted mice were treated with 17 beta-estradiol dipropionate (E2) in a dose of 5 mg/kg and 17 alpha-hydroxy progesterone caproate (Pg) in a dose of 250 mg/kg once a week. After the transferable strain was established, tumors were transplanted into female and male mice treated with E2, Pg, and E2 + Pg. The tumors treated with E2 or E2 + Pg grew exponentially while tumors in the other group regressed. Pg was assumed to play some role in the growth of MCF-7, in the presence of estrogen. Although cytosol estrogen receptors (ERc), nuclear estrogen receptors (ERn), and progesterone receptors (PgR) were detected by dextran coated-charcoal method and exchange assay in the growing tumors, ERn and PgR of regressing tumors was usually negative. This MCF-7 strain in nude mice may be a promising animal model for studying chemo-hormone therapy for human breast carcinomas.

Animals↗

Evidence for the presence of GTP-dependent regulatory component of adenylate cyclase in myelin from rat brain.

A GTP-dependent regulatory component of adenylate cyclase was found in myelin from rat brain. The fraction solubilized from myelin contained a component that reconstituted guanine nucleotide-responsive adenylate cyclase activity when combined with the catalytic unit of adenylate cyclase prepared from rat brain. Purified myelin demonstrated little adenylate cyclase activity, even in the presence of F- or Mn2+. The reconstituted activity was dependent on the amount of the solubilized myelin fraction and required the presence of 5'-guanylylimidodiphosphate, a hydrolysis-resistant analog of GTP. The elution pattern of the component solubilized from myelin in gel filtration was very similar to that of a GTP-dependent regulatory component from synaptic plasma membranes. The content of the regulatory component-like activity in myelin was estimated to be 50-60% of that in synaptic plasma membranes. Cholera toxin ADP-ribosylated proteins having molecular weights of 48,000, 38,000, 23,000, 20,000, and 15,000 and other minor peptides in myelin, some of which were also present in synaptic plasma membranes. We conclude that myelin contained a GTP-dependent regulatory component of adenylate cyclase despite the apparent lack of adenylate cyclase activity in myelin.

Adenosine Diphosphate Ribose↗

Myocardial protection during cardiac ischemia by coronary perfusion with cold lactated Ringer's solution plus mannitol.

This experimental and clinical study evaluates the degree of myocardial protection afforded by coronary perfusion with cold lactated Ringer's solution plus mannitol. In the experimental study, diluted blood at 30 degrees C (Control G.), lactated Ringer's solution at 4 degrees C (G. A), 1,000 ml lactated Ringer's solution plus 200 ml of 20% mannitol at 4 degrees C (G. B), and 1,000 ml lactated Ringer's solution plus 500 ml of 20% mannitol at 4 degrees C (G. C) were used for coronary perfusion. The myocardial-protecting effect of each perfusate was evaluated by examining serum isoenzymes (CPK-MB, LDH1+2), left ventricular function (Vmax, LVEDP, CO), and the ultrastructure of myocardium. there were no significant differences in myocardial changes between the control group, G. A and G. B. Left ventricular enddiastolic pressure increased significantly in G. A and a significant increase in CPK-MB was seen in G. C. Mitochondrial scores for each group were 98 (Control G.), 86 (G. A), 93 (G. B), and 51 (G. C). Minimal myocardial change was seen in G. B. In the clinical study aortic root perfusion with cold lactated Ringer' s solution (400 m Osm) under aortic cross clamping (27-144 min) was employed in 25 patients. They all survived and CPK-MB returned to preoperative values within 49 hours after operation. In 6 cases, the ultrastructure of left ventricular papillary muscle was examined. It was confirmed that no significant mitochondrial changes developed during aortic cross-clamping.

Animals↗

Effects of hypertonic mannitol on renal function in open heart surgery.

An extracorporeal bypass was performed in mongrel dogs for 2 hours with or without hypertonic mannitol infusions. In animals given mannitol, the plasma osmolality was elevated maximally to 344 +/- 7.1 mOsm/L and the urine volume was maintained well during bypass. A hypertonic mannitol solution was effective in maintaining the CPAH during and after bypass, but was not effective in minimizing the reduction in Ccr. When the mean arterial pressure during bypass was kept at 60 mmHg, the carbon filling rates in glomeruli showed the favorable effects of mannitol upon renal function, but no effects were observed at a mean arterial pressure of 80 mmHg. In 11 patients who had undergone a bypass lasting more than 2 hrs with mannitol infusions, the plasma osmolality reflected the serum mannitol level and reached 320 +/- 11.0 mOsm/L at 150 min of bypass. The mean urine volume was 5.0 +/- 3.3 ml/min/M2 during the bypass, which was about 7 times as great as before the bypass. The Ccr increased during the first 30 min of the bypass, but it fell to about one half of the initial value after 90 min of the bypass. It was concluded that a hypertonic mannitol solution is effective in maintaining the RPF and urine volume during and after the bypass and that it also preserved the glomerular perfusion even at a low arterial pressure.

Acute Kidney Injury↗

Catecholamine sensitivity and cardiac myosin ATPase activity in dogs treated with propranolol.

The effects of propranolol treatment on adrenoceptor reactivity and on cardiac myosin ATPase activity have been studied. Eight mongrel dogs weighing 8 to 14 Kg were given propranolol orally 3 times daily (10 mg/Kg/day) for 2 weeks. Although the levels of propranolol were effective and there was a significant decrease in resting heart rate, there was no evidence of a rebound adrenoceptor hypersensitivity after abrupt withdrawal of propranolol treatment. The responsiveness of cardiovascular systems to 1-isoproterenol (1-ISO) was significantly attenuated 15 hrs after the last medication, but it did not differ from the premedication levels 6 days after discontinuation of medication. The effects of 1-ISO on adenylate cyclase activity in the myocardial membrane preparations were not significantly different between the 3 groups (no medication, 1 day and 6 days after discontinuation). With propranolol treatment, though a rise in total plasma catecholamine (norepinephrine, epinephrine, dopamine) levels was the predominant change, there were no definite changes in respective catecholamines. Serum triiodothyronine (T3) increased during medication in 7 of the 8 animals and decreased after medication. Calcium-activated and K+-activated myosin ATPase activity in the inner and outer layers of the left ventricular wall were uniform in unmedicated dogs, and propranolol produced no significant effects. No reliable evidence for propranolol withdrawal syndromes was provided in the present study.

Adenosine Triphosphatases↗

Separation and properties of a regulatory GTPase activity associated with the adenylate cyclase system in rat brain synaptic plasma membranes.

A GTPase activity having a Km value of 0.5 microM was present in synaptic plasma membranes from rat brain. The activity was inhibited 63% and 24% by NaF and cholera toxin respectively and solubilized from the membranes together with the adenylate cyclase activity. Upon gel chromatography, the solubilized GTPase activity was co-eluted with the GTP-binding regulatory protein of adenylate cyclase. A similar GTPase activity was also associated with the regulatory protein from myelin. The regulatory protein fraction enhanced the activity of the catalytic unit of adenylate cyclase in the presence of 5'-guanylylimidodiphosphate but inhibited the adenylate cyclase activity by 70% in the presence of GTP. These results indicate the possible involvement of the GTPase activity in the regulation of the adenylate cyclase activity.

Adenylyl Cyclases↗

[Studies on the effect of lentinan on human immune system. II. In vivo effect on NK activity, MLR induced killer activity and PHA induced blastic response of lymphocytes in cancer patients].

Immunological activities of lymphocytes were studied in patients with cancer of digestive organs and mamma after administration of lentinan. When 11 cancer patients received lentinan i.v. 2 mg, NK activity of lymphocytes was increased in 4 patients on the following day. With the same condition, MLR induced killer activity against Raji cell of lymphocytes was increased in 3/7 patients and PHA response was also increased in 3/7 patients. These activities were returned to values before the administration of lentinan. Then each activity was examined after administration of lentinan twice a week. NK activity, MLR induced killer activity and PHA response were increased in 4/15, 8/12 and 5/11 patients, respectively.

Cytotoxicity, Immunologic↗

Promotion of liver cancer development by brief exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or carbon tetrachloride.

Adult male Fischer rats were exposed to a necrogenic dose (200 mg/kg) of diethylnitrosamine or to nonnecrogenic doses of N-methyl-N-nitrosourea, 1,2-dimethylhydrazine, or benzo(a)pyrene following partial hepatectomy or sham hepatectomy. This treatment by itself led to no hepatocellular carcinomas by 8 to 18 months, except in animals given N-methyl-N-nitrosourea, which showed a 30% incidence by 12 months. With each treatment regimen, exposure to dietary 2-acetylaminofluorene for 2 weeks coupled with partial hepatectomy or the administration of a necrogenic dose of CCl4, was associated with an incidence of 68 to 94% of cancer at 8, 12, or 18 months, depending upon the initiating carcinogen used. Appropriate controls showed either no hepatocellular carcinoma or a much lower incidence. It is concluded that the 2-week exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or the administration of CCl4 has a strong promoting effect on liver carcinogenesis with four different chemical carcinogens.

1,2-Dimethylhydrazine↗

Labeling of a GTP-binding regulatory protein of rat brain adenylate cyclase system by cholera toxin-catalyzed ADP-ribosylation.

Cholera toxin ADP-ribosylated several proteins in synaptic plasma membranes of rat brains such as peptides of 66,000, 48,000, 38,000, 25,000, and 18,000 daltons. A 42,000-dalton protein reported to be the GTP-binding regulatory protein in several tissues was faintly labeled and its content varied from preparation to preparation. Adenylate cyclase activity was concomitantly enhanced by more than twice in proportion to the ADP-ribosylation. Accumulated evidence indicated that a protein of 48,000 daltons (48K protein) was a component which constituted the GTP-binding regulatory protein of adenylate cyclase system in rat brain. Among ADP-ribosylated proteins, the 48K protein was the major substrate for the ADP-ribosylation, and the content of this protein was estimated to be about 15 pmol/mg membrane protein. When synaptic membranes were solubilized and applied on a Ultrogel AcA34 gel filtration column to separate the regulatory protein from other components of adenylate cyclase, the 48K protein--but not other ADP-ribosylated proteins--co-eluted with the regulatory protein activity assayed by the reconstitution with catalytic unit of adenylate cyclase. The 48K protein was also detected in myelin fraction which lack adenylate cyclase activity. When solubilized proteins from myelin were subjected to the gel filtration in the AcA34 column, the regulatory protein activity eluted in the 48K protein fractions where the regulatory protein from synaptic membranes appeared. Myelin contained basic protein-like peptides of 20,000 and 18,000 daltons ADP-ribosylated by cholera toxin. These peptides were solubilized from the membranes with acid. Soluble proteins in brain cytosol were ADP-ribosylated by cholera toxin, which was dependent on the presence of nucleotides.

Adenosine Diphosphate Ribose↗

[Clinical evaluation of adriamycin for advanced breast cancer (3)--a joint study by 26 institutes on the CAF and CMcF treatment].

The clinical efficacy of two combination chemotherapies, "CAF" (cyclophosphamide, adriamycin, fluorouracil) and "CMcF" (cyclophosphamide, mitomycin C, fluorouracil) were evaluated on the patients with disseminated breast cancer. Two dosage levels were prepared for each combination. After the investigators decided the dosage levels for the patients, patients were assigned to either combination chemotherapy, CAF or CMcF. Among those patients, 138 cases were evaluable. The objective response rates according to "Assessment Criteria of Therapeutic Effects on Advanced or Recurrent Breast Cancer" by Japan Breast Cancer Society were as follows; High dose schedule: CAF 48.4% (15/31) CMcF 40.9% (9/22) Low dose schedule: CAF 31.7% (13/41) CMcF 15.9% (7/44) In both dosage levels, CAF produced higher response rate than CMcF: The toxicities commonly encountered in all treatment groups were anorexia, nausea and vomiting, as well as leucopenia. Alopecia in CAF and thrombocytopenia in CMcF were characteristic side effects.

Adult↗

Randomly controlled study of chemotherapy versus chemoimmunotherapy in postoperative gastric cancer patients.

From September 1979 through March 1981, a total of 302 patients with gastric cancer and undergoing gastrectomy at the Department of Surgery at Chiba University Hospital and its 14 affiliated hospitals was studied for clinical effectiveness of immunotherapy with Nocardia rubra cell wall skeleton. The patients were stratified by gross stage of cancer and degree of operative curability. They were then assigned randomly to either chemotherapy group or chemotherapy plus immunotherapy group. Immunotherapy used was intradermal injection of 400 micrograms of N. rubra cell wall skeleton which was given weekly for the first month and monthly thereafter. After the specimen was examined microscopically, the patients were classified by histological stage of cancer and radicality of surgical intervention into curative or noncurative groups. The patients were surveyed for survival period in December 1981. The postoperative survival rate was compared in patients of histologically curative or noncurative resection cases between the two treatment groups. No statistical difference was detected between the groups in age, sex, or operative procedures that might influence the patient's survival. As a result, statistical intergroup difference in survival rates was not seen in patients of the curative group, probably due to a short observation period. However, the intergroup difference in survival rates was statistically significant in patients of the noncurative group (p less than 0.01). These results indicate the adjunctive effect of N. rubra cell wall skeleton as an immunotherapeutic agent in patients undergoing gastrectomy for gastric cancer.

Adult↗