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S Yano

Publications and source records attributed to S Yano.

At least 451 records · Page 25Linked to original sources

Lysis of human alveolar macrophages by lymphokine-activated killer cells.

In order to determine if human LAK cells were cytotoxic against autologous AM phi, we studied the ability of human peripheral blood MNCs, stimulated in vitro with recombinant human IL-2, to lyse AM phi in a four-hour 51Cr-release assay. These cells showed significant cytotoxicity against autologous AM phi. The AM phi which had been cultured for four days served as better targets than freshly isolated AM phi. Kinetic study showed that the lysis of AM phi was proportional to the incubation time of MNCs with IL-2 and that LAK cells against AM phi required two days of in vitro culture with IL-2 for their induction. Freshly isolated MNCs did not lyse AM phi but did lyse K562 target cells, indicating that AM phi are natural killer-resistant. The phenotypes of effector cells against AM phi were found to be CD8+ or CD16+ (or both). These studies indicate that IL-2 can generate LAK cells against autologous AM phi, and this cytolytic activity must be taken into account when IL-2 or LAK cells are used for immunomodulation in patients with cancer.

Bronchoalveolar Lavage Fluid↗

Inhibition of natural killer cell activity by oral administration of theophylline.

Asthmatic patients have a low incidence of malignancies, and this is possibly due to higher NK cell activity in this population. Because theophylline is used widely in this population, we evaluated the influence of theophylline on NK cell activity in vitro and in vivo. The NK cell activity was significantly inhibited by direct addition of concentrations of aminophylline that exceeded 5 x 10(-5) M. To test whether such an effect can be observed in vivo, we administered one sustained-release tablet of theophylline (400 to 500 mg twice daily) to five normal volunteers for seven days. Significant inhibition of NK activity was noted after administration (mean percentage of inhibition, 41.3 percent), but the serum concentrations observed gave a mean value of 2 x 10(-5) M, which was lower than that yielding the same degree of inhibition by direct addition in vitro (about 20 x 10(-5) M). These results suggest that long-term theophylline therapy may inhibit NK cell activity, and thus more information would be needed to determine the position of such therapy in the management of asthmatic patients.

Administration, Oral↗

Effect of glycyrrhizin on the pharmacokinetics of prednisolone following low dosage of prednisolone hemisuccinate.

We investigated the pharmacokinetics of prednisolone (PSL) in six healthy men, with or without glycyrrhizin (GL), to confirm whether GL influences the metabolism of PSL in humans. Each subject received an intravenous administration of 0.096 mg/kg of prednisolone hemisuccinate (PSL-HS, equivalent to 0.075 mg/kg of PSL), with or without 200 mg of GL. Blood samples were taken from a peripheral vein at 5, 10, 15, 30 and 45 min, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 h after PSL-HS infusion. The concentration of total PSL in the plasma was analyzed by high-performance liquid chromatography, and the free PSL was measured by an isocolloidosmolar equilibrium dialysis method. The pharmacokinetic parameters of PSL were determined, using noncompartmental analysis. GL was found to increase significantly the concentration of total PSL at 6, 8 h, and of free PSL at 4, 6, and 8 h after PSL-HS infusion. GL was also found to modify the pharmacokinetics of PSL. After the administration of GL, the area under the curve (AUC) increased, total plasma clearance (CL) decreased, and the mean residence time (MRT) was prolonged. However, only those of AUC, CL, and MRT of free PSL were significantly different. The volume of distribution at a steady-state (Vdss) of both total and free PSL showed no evident change. This suggests that GL increases the plasma PSL concentrations by inhibiting the metabolism of PSL and that it potentiates pharmacological effects of PSL.

Adult↗

Molecular cloning and DNA sequence analysis of preproinsulin genes in the NON mouse, an animal model of human non-obese, non-insulin-dependent diabetes mellitus.

Two insulin genes of the NON mouse, an animal model of human non-obese, non-insulin-dependent diabetes mellitus, were isolated and characterized to examine the hypothesis that these genes are structurally different from those of normal mice. The NON mouse was found to have two non-allelic insulin genes, as does the normal mouse, and no structural differences were found between the normal and NON mouse in the nucleotide sequence of the insulin gene, including that of the 5'-transcriptional regulatory region, and in the deduced amino acid sequence. There was, however, an additional 113 bp sequence and seven point mutations in a further 5'-flanking region, and three point mutations in the 3'-flanking region of the insulin II gene. We conclude that reduced expression of insulin genes in the NON mouse is not due to the structural change in the known transcriptional regulatory region, although the effect on insulin II gene expression of an additional sequence upstream of the 5'-flanking region, as the negative regulatory factor, remains to be elucidated.

Alleles↗

Clinical and pathological evaluation of early cancer in the gastric cardia.

We report 9 rare cases (7 males and 2 females) of early gastric cancer of the esophagogastric junction. From 1976 to 1988, 1308 cases of gastric cancer were resected in our Institute. Of these, 479 (36.6%) cases were early gastric cancer. Among all 479 early gastric cancers, 9 (1.9%) were located within 2 cm of the esophagogastric junction on the lesser curvature and/or posterior wall of the cardia. This represents 11.7% (9/77) of the cases of cancer at the esophagogastric junction. This incidence contrasts with the 39.5% of early cancers elsewhere in the stomach. Overall, 36.6% (479/1308) were early gastric cancer. Eight of these 9 patients were resected through the abdominal approach and one by the thoracoabdominal approach. Seven underwent proximal and 2 underwent total gastrectomy. On microscopic examination, one cancer was m-cancer, and 8 were sm-cancer. Lymphnode metastasis was found to be absent in all 9 cases. The prognosis of cancer of the cardia is generally poorer than that for adenocarcinoma in the corpus or distal stomach. However, cancer recurrence 22-91 months postoperatively was zero in these 9 cases of early gastric cancer at the esophagogastric junction.

Cardia↗

Retrospective studies of gastric cancer with hepatic metastases.

From 1979 to 1988, a total of 1265 cases of gastric cancer were admitted to our Institute. Of these, 80 cases (6.3%) involved hepatic metastasis. Thirty-eight cases (47.3%) underwent gastrectomy (24 distal, 2 proximal, 11 total and one partial). Of these 38 cases, 7 underwent a combined resection of a simultaneous metastatic hepatic tumor. A total of 19 (67.9%) of the 28 cases in H1, 6 (37.5%) of the 16 cases in H2, and 13 (36.1%) of the 36 cases in H3 underwent gastrectomy. Hepatic metastasis occurred most frequently (18.2%) in Borrmann type 1, 5% in type 2, 14.9% in type 3 and 8.7% in type 4. Of all 593 resected advanced cases, there were 283 differentiated type, with a hepatic metastasis rate of 14.5%, and 310 undifferentiated type with 7.1% rate of hepatic metastasis. In H1 and H2, the prognosis after primary gastric cancer resection was better than for unresected cases. Moreover, there have been reports recently of long-term survival using continuous hepatic arterial infusion of anti-cancer drugs, and of combined resection of the metastatic hepatic tumor after curative gastrectomy. Therefore we should not give up these H1 and H2 patients.

Adult↗

[Effects of granulocyte colony-stimulating factor on peripheral white blood cell and platelet counts in mice pretreated with anticancer drugs].

Effects of human recombinant granulocyte colony-stimulating factor (G-CSF) on peripheral white blood cell (WBC) and platelet (PLT) counts were examined in BALB/c mice pretreated with various kinds of anticancer drugs. Significant increase of WBC and significant decrease or tendency to decrease of PLT count were observed in mice treated with ACNU (40 mg/kg), CY (150 mg/kg), MMC (8 mg/kg) or VDS (3 mg/kg) followed by G-CSF treatment. These results indicate that we should study more about a possibility that treatment with G-CSF and anticancer drugs may cause in man a more severe thrombocytopenia than is observed with only chemotherapy treatment.

Animals↗

Effects of granulocyte colony-stimulating factor on hematopoietic injury induced by anticancer drugs in mice.

The in vivo effects of the subcutaneous administration of the granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced hematopoietic injury were evaluated in BALB/c mice. Mice treated with chemotherapeutic drugs were injected once a day for up to 12 days with 2 micrograms of recombinant human G-CSF, and following this, bone marrow cellularity, spleen weight, and peripheral blood cell counts were measured 24 h after cessation of the G-CSF treatment. Treatment of normal mice had minimal effect on the elevation of the white blood cell (WBC) count or on the hosts' resistance to K. pneumoniae infection. Spleen weight was significantly higher in normal mice treated with G-CSF, and the platelet counts were slightly lower. In mice treated with cyclophosphamide (150 mg/kg), G-CSF treatment caused an elevation of WBC and an enhancement of antibacterial resistance. Variable amounts of an accelerated recovery of neutrophils by G-CSF treatment was also observed in nimustine hydrochloride (50 mg/kg)-, mitomycin c (MMC) (8 mg/kg)-, or vindesine sulfate (VDS) (4 mg/kg)-treated mice. A significant decrease in PLT counts was observed in MMC- or VDS-treated hosts given G-CSF. These results indicate that administration of G-CSF may facilitate hematopoietic recovery in chemotherapy-treated cancer patients and that it may help them to increase their resistance to life-threatening infection. Conversely, treatment with G-CSF and chemotherapeutic drugs may cause a more severe thrombocytopenia than is observed with only chemotherapy treatment.

Animals↗

[Clinical study on bronchial asthma patients whose bronchial hypersensitivity has been improved].

In order to determine which factors would affect the improvement of bronchial hypersensitivity in asthmatic patients, a clinical investigation was performed on 42 cases whose bronchial hypersensitivity had been tested more than two times. The following results were obtained. 1) The numbers of bronchial hypersensitivity-improved cases was 16 while there were 26 unimproved cases. There was no statistical difference in age, sex, type of asthma, severity of disease at first visit or type of therapy between the two groups. FEV1.0% in the bronchial hypersensitivity-improved group was significantly higher than that in the unimproved group (p less than 0.01). 2) In the improved group, all cases (16/16) were shown to have become free of symptoms, but this applied to only 38% (10/26) in the unimproved group. 3) In the 26 cases who had become free of symptoms, the improvement index in histamine test and the ratio of improved cases showed a tendency to increase as the period during which the patient showed no symptoms extended. It was suggested that bronchial hypersensitivity in cases with higher FEV1.0% would improve more easily, and that the induction and maintenance of a symptom free state is important for the improvement of bronchial hypersensitivity.

Adult↗

Effects of prostaglandin E1 on collagen diseases with high levels of circulating immune complexes.

Prostaglandin E1 (PGE1) was administered to 4 patients with collagen diseases presenting with high levels of circulating immune complexes (CIC) in sera. Our study patients had progressive systemic sclerosis, systemic lupus erythematosus, polyarteritis nodosa, and rheumatoid arthritis. In all 4 patients, CIC levels significantly decreased after administration of PGE1 by continuous infusion at 10/ng/kg/min via central venous catheter for 72 h. In addition, the skin ulcer in a patient with PSS healed completely, and the finger necrosis in a patient with RA improved. These results suggest that PGE1 given by continuous venous infusion is effective in reducing CIC, in addition to improving peripheral vascular disorders.

Adolescent↗

Increasing effect of sodium 3-ethyl-7-isopropyl-1-azulenesulfonate 1/3 hydrate (KT1-32), a novel antiulcer agent, on gastric mucosal blood flow in anesthetized.

Effect of a novel azulene derivative KT1-32 on gastric mucosal blood flow (GMBF) was studied to elucidate its mucosal defensive mechanisms underlying the antiulcer action. The GMBF was measured by two methods which were based on heat clearance and laser Doppler velocimetry in the rat. Intravenous administration of KT1-32 produced a dose-dependent increase in GMBF at doses of 0.3-10 mg/kg; significant increases in GMBF were observed at doses not less than 1 or 3 mg/kg by the laser Doppler or heat clearance method, respectively. The duration of action was about 10 min at 10 mg/kg of KT1-32. A good parallelism in these GMBF changes was noted between both methods. Cetraxate, an antiulcer agent, elicited an increase in GMBF at 30 mg/kg, i.v., when GMBF was measured by the heat clearance method. Sodium guaiazulene 3-sulfonate, another azulene antiulcer agent, showed no increase in GMBF. It is suggested that the increasing effect of KT1-32 on GMBF contributes to its antiulcer activity through strengthening mucosal defensive mechanisms.

Anesthesia↗

[A case of antithrombin III abnormality presenting as bronchial asthmatic symptom due to pulmonary thromboembolism].

A 32-year-old housewife with AT III abnormality visited our out-patient clinic because of dyspnea on April 14, 1988, and was diagnosed as bronchial asthma of non-atopic type. In spite of treatment, her asthmatic symptom did not improve. Therefore, she was admitted to our department on August 12 for a detailed examination and more effective therapy. Xanthine derivatives and beta 2 stimulant were ineffective, and only steroid hormone was effective to some degree. Pulmonary perfusion scan revealed that her pulmonary thromboembolism had become worse. Then she was treated with AT III concentrate and urokinase and her asthmatic symptom was significantly improved and steroid hormone could be easily reduced. Her asthmatic symptom was suggested to be due to progression of pulmonary thromboembolism. We were not able to find any other report of a case with AT III abnormality presenting as bronchial asthma due to pulmonary thromboembolism.

Adult↗

[The clinical studies of intermittent hepatic artery occlusion with infusion chemotherapy--19 cases of unresectable hepatocellular carcinoma and 14 cases of metastatic liver cancer].

For unresectable liver tumors, intermittent occlusion of the feeding artery by means of surgical placement of double lumen balloon catheter in the hepatic artery was combined with chemotherapy. Through the catheter, fluorouracil was continuously infused and one-shot injections of mitomycin or adriamycin were given at the time of balloon inflations. Nineteen patients with primary hepatocellular carcinoma (7 were at Stage III and 11 were at Stage IV) and 14 patients with metastatic liver tumors (4 were at H2 and 9 were at H3 stages) received this newly developed anticancer methodology. In terms of Karnofsky's criteria, 17 of 19 cases with hepatocellular carcinoma achieved Group I responses (89.5%). Fourteen were classified to I-B (73.7%), and one year survival rate was 51.6%. Of 14 cases with metastatic tumors, 13 achieved Group I responses (92.9%). Five were classified to I-B (35.7%), and one year survival was 23.1%. Intermittent occlusion method has advantages in minimizing adverse effects, enabling controlled arterial infusion of anticancer agents and stepwise occlusion of the feeding artery. Despite advanced stages and poor conditions of the patients, remarkable responses were achieved without any serious problems. We are at a conclusion that intermittent occlusion of the hepatic artery when combined with infusion-chemotherapy would, in synergism, be a potential modality against unresectable liver tumors.

Adult↗

Butyrate increases catalase activity and protects rat pulmonary artery smooth muscle cells against hyperoxia.

A protective effect of butyrate against hyperoxia was found with adult rat pulmonary artery smooth muscle cells. Butyrate (5mM) when added just prior to the hyperoxic exposure (95%) markedly decreased lactate dehydrogenase release from cells during 68 hours of exposure (22% release with butyrate versus 98% without). The uptake and reduction of a tetrazolium compound as another index of cell viability also showed similar improvement with butyrate. Butyrate was associated with a striking increase of catalase to three times the control in the air exposed group while GSH content and the activities of superoxide dismutase and glutathione peroxidase were not significantly changed. In the groups exposed to hyperoxia alone, both enzyme activities were decreased compared to the air exposed controls. When butyrate was present with hyperoxia, the superoxide dismutase was maintained closer to the air exposed control values and the catalase activity remained nearly twice as high as the air exposed control cells. These results suggest that butyrate protects rat pulmonary artery smooth muscle cells from hyperoxia by increasing catalase activity which may help to preserve superoxide dismutase activity. This may be a good model to determine the biological significance of catalase and its interrelationships with other antioxidant systems within the cell.

Animals↗

The establishment of Epstein-Barr virus nuclear antigen-positive (SP-50B) and Epstein-Barr virus nuclear antigen-negative (SP-53) cell lines with t(11;14)(q13;q32) chromosome abnormality from an intermediate lymphocytic lymphoma.

Two lymphoma cell lines, SP-50B and SP-53, were established from peripheral blood of a 58-year-old woman with leukemic conversion of intermediate lymphocytic lymphoma. These cell lines grew in suspension with or without forming clumps of cells. SP-50B was morphologically similar to the common Epstein-Barr (EB) virus-transformed lymphoblastoid cell lines and was positive for EB virus nuclear antigen (EBNA), whereas SP-53 closely resembled the patient's lymphoma cells and was negative for EBNA. Both cell lines expressed the same phenotypic markers as original lymphoma cells (CpIg+, SmIg+, OKIa1+, Leu12+) and possessed t(11;14)(q13;q32) chromosome translocation. These results indicate that although morphologically different, SP-50B and SP-53 were both derived from patient's lymphoma cells. The long-term cultivation of EBNA-positive and EBNA-negative B-cell lymphoma lines from a single donor has not been previously reported. These cell lines would provide useful tools for studying the oncogenic role of EB virus and bcl-1 oncogene that is located on chromosome 11q13.

Antigens, Viral↗

Most effective route of administration and utilization of high-dose chemotherapy with bone marrow transplantation in rats.

In order to find out which anticancer drugs could utilize to the best advantage a syngeneic bone marrow transplantation in high-dose chemotherapy for cancer, we tested six drugs [nimustine hydrochloride (ACNU), Adriamycin, cyclophosphamide (CY), mitomycin c, vindesin, etoposide] in Sprague-Dawley rats from a standpoint of the beneficial effect of bone marrow transplantation (BMT). Two or three varying doses of each drug were administered i.v. on Day 0, followed by the injection of syngeneic bone marrow (BM) cells (5 x 10(7), i.v.) on Day 2, and the animals were observed for over 60 days. Adriamycin caused high rates of peripheral neuropathy, and was therefore judged to be inappropriate for high-dose chemotherapy-BMT in this animal model. Among the other five drugs, a beneficial effect of BMT was observed only with CY (300-400 mg/kg) and ACNU (40 mg/kg). In order to enhance the beneficial effect of BMT observed with CY and ACNU, a way of drug administration was designed and carried out. Consequently a higher survival rate was obtained in the following experimental groups: (a) (CY 200 mg/kg, Days 0 and 1) + BMT greater than (CY 400 mg/kg, Day 0) + BMT, (ACNU 20 mg/kg, Days 0 and 1) + BMT greater than (ACNU 40 mg/kg, Day 0) + BMT. (b) (CY 200 mg/kg + ACNU 20 mg/kg, Day 0) + BMT greater than (CY 400 mg/kg or ACNU 40 mg/kg, Day 0) + BMT. (c) (CY 200 mg/kg, Day 0) + (ACNU 20 mg/kg, Day 1) + BMT greater than (ACNU 20 mg/kg, Day 0) + (CY 200 mg/kg, Day 1) + BMT. Among the six anticancer drugs tested in this study, CY and ACNU were suggested to be more appropriate drugs for high-dose chemotherapy-BMT, but methods for reducing drug toxicity (dose, combination, sequence) were necessary so as to enhance the beneficial effect of the BMT.

Animals↗