Search PubMedSearch

Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 163 records · Page 9Linked to original sources

Alterations in DNA synthesis and cellular constituents in mouse lung following bleomycin injections.

Changes in the DNA synthesis and cellular constituents of mouse lung following repeated bleomycin (BLM) injections were studied. ICR mice were administered BLM subdermally for 10 days. Wet lung weight was increased 1.36 times on day 5 after the final administration compared with control mice receiving an identical volume of saline only for 10 days. The total number of cells in the bronchoalveolar lavage fluid of the BLM group reached a maximum on day 14, and histologic investigation of the lungs revealed marked cellular infiltrations. The labeling index obtained by the antibromodeoxyuridine monoclonal antibody method for cells was increased from days 5 to 14 in the BLM group. By day 28, these inflammatory changes had subsided and fibrotic remodeling had occurred. DNA polymerase activity in the lung tissue reached its maximal level on day 5 and remained unchanged until day 14. This phenomenon occurred in parallel with increases in DNA content and synthesis. During this period, an increase in DNA polymerase-beta activity and new induction of DNA polymerase-alpha activity were observed by phosphocellulose column chromatography. From these observations, it is concluded that: (1) repeated injections of BLM cause DNA injury in lung cells; (2) there is a subsequent increase in the DNA repair function as supported by the finding of an increase in DNA polymerase-beta activity; and (3) these lead further to cell proliferation as supported by the increase in both DNA polymerase-alpha activity and DNA content. Thus, a close relationship between morphologic changes and altered DNA synthesis was observed in the lungs of mice after BLM injections.

Animals

The blood vascular bed of the human pancreas, with special reference to the insulo-acinar portal system. Scanning electron microscopy of corrosion casts.

Microdissection and scanning electron microscopy of corrosion casts showed the structures of the vascular bed of the human pancreas to consist mainly of the capillary plexuses of the exocrine lobules, extralobular ducts and endocrine islets. A considerable number of the exocrine lobules were found to contain one to four marked endocrine islets larger than 30 microns in diameter. These intralobular islets received one or more arterioles (afferent vessels) and emitted conspicuous insulo-acinar portal vessels which continued into the lobular capillaries, suggesting insular control over the functions of the exocrine acini of the pancreas. Direct drainage of the intralobular islets into the veins was never reproduced. Not excluding the possibility that some lobules might contain smaller, unidentifiable islets, there nonetheless were many lobules which directly received arterioles. These lobules are free of control by an islet. Rarely, an islet was located in the interlobular tissue space or along an extralobular duct. Such an extralobular islet issued no portal vessels, and drained into the interlobular or periductal veins. The surface of this type of islet comprised a thin network of fine capillaries. A possibility was suggested that this cortical network might be homologous with the lobular capillaries. No portal route was observed between the islets and extralobular ducts. Few connections were noted between the capillary plexuses of the lobules and ducts.

Adult

Coronary artery disease in patients with arteriosclerosis obliterans of the lower extremities or aortic aneurysm.

Routine coronary angiography was performed in order to determine the incidence and clinical condition of coronary artery disease in 37 patients with arteriosclerosis obliterans or aortic aneurysm. Coronary angiography demonstrated significant stenosis in 12 (57%) of 21 patients with arteriosclerosis obliterans and in 7 (44%) of 16 patients with aortic aneurysm. The prevalence of risk factors for arteriosclerosis was similar for patients with arteriosclerosis obliterans and those with aortic aneurysm, and similar for patients with and without coronary artery stenosis. But coronary artery disease is often silent in patients with arteriosclerosis obliterans.

Aged

DNA synthesis and related enzymes altered in compensatory lung growth in rats.

Left pneumonectomy was performed on 4 week-old male Fischer-344 rats. Changes in DNA biosynthesis and the activities of related enzymes were studied in the contralateral lungs of the pneumonectomized animals (n = 55) and compared with sham-operated (n = 55) and untreated control animals (n = 40) The wet weight of the contralateral lung of the pneumonectomized rats reached that of both lungs of the untreated and sham-operated rats 14 days after the operation. The activities of thymidine kinase and DNA polymerase from the regenerating lungs were elevated on Days 1 and 7. To determine the molecular forms of DNA polymerase in the crude extract, phosphocellulose column chromatography was performed. The type of DNA polymerase with the highest activity was alpha in regenerating lung on Days 1, 3, and 7. These results suggest that DNA replication for cellular proliferation was elevated in the remaining lung after pneumonectomy. In addition, an interlobar difference in DNA biosynthesis was observed in the remaining lung. The increase was especially marked in the cardiac lobe, followed by increases in the DNA content of the remaining lobes on Day 7. From these observations we conclude (1) that increased activity of DNA polymerase alpha is likely to be an initial change in compensatory lung growth, and may be caused by some unknown stimulator in lung tissue, and (2) that DNA biosynthesis may differ among the lobes of the lung, at least until 3 days post-pneumonectomy.

Animals

Pokeweed mitogen induces p55 interleukin-2 receptor expression on human monocytes and its effect on interleukin-2 activated monocyte cytotoxicity.

Activation of human peripheral blood monocytes by pokeweed mitogen (PWM) results in the expression of interleukin 2 receptor(IL-2R) p55 chains, which are absent on resting monocytes. By dual-fluorescence flow cytometry, we found PWM induced detectable numbers of IL-2R+ cell which were further identified as LeuM3+ monocytes (22.91% of the LeuM3+ cells were IL-2R+ within 24h, and 32.17% in 48h). In addition, LPS can also induce IL-2R on 15.39% of LeuM3+ cells. On the contrary, other mitogens such as PHA or Con A, and cytokines as IFN-gamma, IL-2, M-CSF, TNF-alpha and IL-1 beta showed no influence on the IL-2R expression on monocytes. It was also noticed that PWM itself had no direct effect on HLA-DR antigen expression on LeuM3+ cells. The addition of IL-2 to PWM-pretreated IL-2R positive monocytes significantly augmented their tumoricidal activity. Thus monocytes when activated underwent a series of phenotypic and functional changes including the expression of IL-2R which may provide an important immunoregulatory pathway.

Cytotoxicity, Immunologic

[Co-operative clinical evaluation of 5'-DFUR tablets for breast cancer at 31 institutions].

A phase II study of 5'-deoxy-5-fluorouridine (5'-DFUR) tablets for breast cancer was done at 31 institutions in Japan. Forty-five patients were registered and 44 of them were eligible for the study. Of the 40 patients whose results could be evaluated, 11 (28%) responded (four complete responses and seven partial responses). Side effects, such as diarrhea, anorexia, leukocytopenia, and liver dysfunction were observed in 24 of the 44 patients. The side effects were mild and transient. 5'-DFUR is a promising drug for breast cancer treatment, and its tablet form makes chemotherapy easier for the patient.

Administration, Oral

[Combination therapy of doxifluridine (5'-DFUR) + cyclophosphamide (CPA) + tamoxifen (TAM) for advanced or recurrent breast cancer. Joint Research Group in the Osaka Area for Combination Therapy of 5'-DFUR with Other Drugs].

Outpatients with advanced and recurrent breast cancer were treated by a combination therapy of the following drugs: doxifluridine (5'-DFUR) orally administered at a dose of 1200 mg/day; cyclophosphamide (CPA) orally given at dose of 100 mg/day; and tamoxifen (TAM) orally given at dose of 20 mg daily. 5'-DFUR and CPA were administered on consecutive days 1-14, then discontinued for 14 days. The response rate was 44.8% including five CR and eight PR out of 29 complete cases. As for response cases in terms of the subject lesions, corresponding cases were chiefly found in soft tissue and the lung. As for the response rate with or without pretreatment, cases previously treated showed a higher response rate such as 42.9% indicating that the present therapy was effective in pretreatment cases. The main side effect was leukopenia, but not so severe. Few cases with diarrhea were found. Based on the above findings, the present treatment is conceivably a highly useful therapy, on an outpatient basis, for advanced and recurrent breast cancer, especially metastatic lesions of soft tissue and the lung.

Administration, Oral

[Clinical evaluation of ondansetron (injection of a single intravenous dose) against nausea and emesis associated with anti-cancer drugs--dose-finding study in patients receiving cisplatin].

We examined anti-emetic effects, safety and the optimal dose of Ondansetron Injection given in a single intravenous dose in patients receiving a single high dose of cisplatin in randomized controlled comparative study using telephone registration. Ondansetron was injected intravenously in a single dose of 4 mg, 8 mg or 12 mg, at 15 minutes before administration of cisplatin. Nausea and emesis were observed for 24 hours after administration of cisplatin. Efficacy rate of inhibitory effects on nausea and emesis were 76% (19/25 cases) in the 4 mg dose group, 57% (12/21 cases) in the 8 mg dose group and 83% (20/24 cases) in the 12 mg dose group, without a statistically significant difference among 3 dose groups. Hence, it was estimated that the low dose of 4 mg was adequate to exert satisfactory anti-emetic effects. No clear relationship between onset time of the initial emetic episode and plasma concentrations of Ondansetron was found in 16 cases of the 4 mg dose group, 11 cases in the 8 mg dose group and 15 cases in the 12 mg dose group. Side effects observed during this study period were headache and diarrhea in 1 case in the 12 mg dose group. Both symptoms were mild and resolved without treatment. No abnormal findings attributable to Ondansetron were observed in clinical laboratory test. From the above, it was considered that Ondansetron given by a single intravenous injection was highly effective to inhibit nausea and emesis induced by cisplatin, and was highly safe. As to the dose, 4 mg once daily was considered to be adequate for prophylaxis of cisplatin-induced nausea and emesis.

Adult

[Examination of anti-emetic effect, safety and usefulness of single oral dose of ondansetron tablet in nausea and emesis induced by anti-cancer drugs--dose-finding study of ondansetron tablet in patients receiving non-platinum anti-cancer drugs].

Inhibitory effects on acute nausea and emesis, safety and usefulness of a single oral dose of Ondansetron tablet were evaluated in 3 different dose levels for comparison by telephone registration system, in patients receiving non-platinum anti-cancer drugs. A single dose of ondansetron at 4 mg, 8 mg or 12 mg was given orally at 2 hrs before the initial administration of anti-cancer drugs. The patients were observed for 24 hours after administration of anti-cancer drugs, for occurrence of nausea and emesis. Efficacy rates of inhibitory effects on nausea and emesis were 83.3% (10/12 cases) in 4 mg dose group, 78.6% (11/14 cases) in 8 mg dose group and 84.6% (11/13 cases) in 12 mg dose group, without statistically significant difference. Side effects were observed in 3 cases (headache, cold feeling and trembling in limbs, sleepiness) in 12 mg dose group, but these symptoms were not severe and disappeared after several hours or several days. No abnormality in clinical laboratory findings attributable to Ondansetron was observed. From the above, it was considered that Ondansetron was a clinically useful anti-emetic for nausea and emesis induced by non-platinum anti-cancer drugs and that 4 mg once daily was the optimal dose.

Administration, Oral

[Anti-emetic effect and safety of consecutive use of ondansetron injection in cisplatin-induced nausea and emesis].

Anti-emetic effect, safety and clinical usefulness of Ondansetron injection given in the dose of 4 mg once daily by intravenous administration for 3-5 consecutive days were examined in patients receiving a high single dose (not less than 50 mg/m2 or over 75 mg/body) and lower multiple doses (over 15-20 mg/m2 once daily, for 3-5 consecutive days) of cisplatin. Efficacy rates of inhibitory effects on nausea and emesis in patients receiving the high single dose of cisplatin were 76% on the 1st day, 67% on the 2nd day and 78% on the 3rd day, the average being 71% (86/121 cases) for the 3 days. Those in patients receiving lower multiple doses of cisplatin were 83% on the 1st day, 78% on the 2nd day, 61% on the 3rd day, 65% on the 4th day and 57% on the 5th day, the average being 72% (13/18 cases) for the 3-5 days. Side effects were observed in 15 cases out of 207 (1st course, 182 cases; 2nd course, 21 cases; 3rd course, 4 cases), and major symptoms were headache and fever. Also, abnormalities in clinical laboratory findings attributable to Ondansetron were observed in 13 cases, mainly consisting of elevation of the hepatic function values. From the above, Ondansetron injection which showed sufficient anti-emetic effects on acute emesis and delayed emesis induced by a high single dose or lower multiple doses of cisplatin with its once daily intravenous dose given for 3-5 consecutive days, were considered a safe and clinically useful anti-emetic.

Aged

[Examination of anti-emetic effect and safety of multiple intravenous doses of ondansetron in patients receiving nonplatinum anti-cancer drugs].

Anti-emetic effects, safety and usefulness of Ondansetron given intravenously at 4 mg once daily for consecutive 3-5 days were investigated against nausea and emesis induced by non-platinum anticancer drugs. Efficacy rates in control of nausea and emesis were 59% (20/34 cases) and 68% (23/34 cases), respectively. The efficacy rate for inhibition of nausea and emesis, calculated based on the control of nausea and emesis, was 68% (23/34 cases). Adverse events (headache and constipation) were observed in 1 case and abnormal change in clinical laboratory findings (increase in eosinophil count) in another case. Out of 42 cases in which safety was evaluated, 41 (98%) cases were assessed as "no problem in safety." However, one case with side effect was assessed as a "Minor problem in safety." From the above, it was confirmed that Ondansetron injection exerted excellent inhibitory effects against nausea and emesis induced by non-platinum anti-cancer drugs, and this drug was a highly safe and useful anti-emetic.

Adolescent

[Investigation of anti-emetic effect of ondansetron tablet in multiple doses on nausea and emesis associated with cisplatin].

The anti-emetic effects, safety and usefulness of ondansetron, a 5-HT3 receptor antagonist, given orally once daily for 3-5 consecutive days, were investigated in patients receiving a high single dose (greater than or equal to 50 mg/m2 or 75 mg/body) or lower multiple doses (greater than or equal to 15-20 mg/m2/day for 3-5 consecutive days) of cisplatin. Ondansetron 4 mg was administered orally once daily for 3-5 consecutive days. Efficacy rates in controlling nausea and emesis over the 3-5 days were 77.3% (17/22 cases) and 66.7% (6/9 cases) in patients receiving a high single dose and lower multiple doses of cisplatin, respectively. Side effects were observed in 2 cases (headache and elevation of blood pressure in one case and only headache in the other case.). Abnormality in clinical laboratory findings was observed in 1 case. From the above, ondansetron, showing high efficacy by oral administration 4 mg once daily for 3-5 consecutive days, without any problem in safety, was considered to be a useful anti-emetic agent.

Administration, Oral

[Examination of inhibitory effect, safety and usefulness of SN-307 (ondansetron) administered orally once daily for 3-5 consecutive days on nausea and emesis associated with non-platinum anti-cancer drugs].

We examined the anti-emetic effect, safety and usefulness of ondansetron hydrochloride, a selective 5-HT3 receptor antagonist, given orally once daily at the dosage of 4 mg, for 3 to 5 consecutive days to patients with nausea and emesis induced by non-platinum anti-cancer drugs such as cyclophosphamide, doxorubicin and carboplatin. Out of 84 cases where anti-emetic effects were evaluated, numbers of cases assessed as excellent and good were 36 (83.3%) and 34 (40.5%), respectively, the efficacy rate being 83.3% (70/84). Side effects, such as moderate constipation (3 cases) and mild headache (3 cases), were observed in 8/85 cases (9.4%). Abnormalities in clinical laboratory findings including elevation of hepatic function and uricacid values and increase in eosinocyte counts, were observed in 3/85 cases (3.5%). As to overall safety, 78/85 cases (91.8%) were evaluated as having no problem in safety, and 7/85 cases (8.2%), as having minor problem in safety. As to clinical usefulness based on anti-emetic effect and overall safety, out of 79 cases the drug was assessed as very useful in 29 cases (36.7%) and useful in 35 cases (44.3%), the rate of "useful" or above being 81.0% (64/79). Furthermore, when ondansetron was administered in 3 courses of chemotherapy, though the number of patients was small, it was shown that anti-emetic effect of ondansetron did not decline and no problem in safety was observed. From the above, ondansetron which exerted adequate anti-emetic effect in 4 mg once daily doses was considered as a useful and safe anti-emetic in treatment of nausea and emesis associated with cancer chemotherapy.

Administration, Oral

[Evaluation of SN-307 (ondansetron), given intravenously for the treatment of nausea and vomiting caused by anticancer drugs including cisplatin-open study].

The anti-emetic effect, safety and clinical usefulness of ondansetron for the treatment of nausea and vomiting caused by anticancer drugs including cisplatin, was evaluated by a multi-institutional study in patients with various malignancies. In this study, ondansetron was given intravenously with mainly a single dose of 4 mg to intervene nausea and vomiting. 1. Efficacy ratio of overall effects on nausea and emesis observed for 24 hours after treatment was 69.8%. 2. No side effect was observed. Laboratory tests showed temporary elevation of serum uric acid level in 1 patient in the group given 4 mg. 3. From these results, it seems that ondansetron, given intravenously after initial vomiting, was highly safe and clinically useful anti-emetic for the treatment of nausea and vomiting associated with anti-cancer drugs.

Adult

[Anti-emetic effect and safety of single dose of ondansetron injection in double-blind comparison study with placebo].

In order to make an objective evaluation of anti-emetic effect, safety and usefulness of ondansetron injection in nausea and vomiting associated with cancer chemotherapy, we carried out a double-blind placebo controlled comparative study in patients receiving high-single dose (50 mg/m2 or more) of cisplatin. Either 4 mg of ondansetron or saline injection was given intravenously at 15 min. before administration of cisplatin. If anti-emetic effect of the test drug was insufficient, an additional dose of 4mg of ondansetron was given intravenously, as the rescue medication. Ondansetron was significantly superior to placebo in anti-emetic effect (p < 0.001). Efficacy rates were 66.7% (22/33 cases) in ondansetron and 20.0% (6/30 cases) in placebo groups. Seven and 21 cases required rescue medication with 4 mg single intravenous dose of ondansetron due to insufficiency of anti-emetic effect, in ondansetron group and placebo group, respectively. Thus the number of patients who required rescue medication was obviously greater in placebo group than that in ondansetron group. The rates of inhibitory effect of rescue medication on nausea and emesis were 14.3% (1/7 cases) in ondansetron group and 61.9% (13/21 cases) in placebo group. Side effects were observed in 1 case (eruption) in ondansetron group and in 2 cases (headache, diarrhoea; 1 case each) in placebo group. Furthermore, fever developed in 1 case in placebo group after the rescue medication. Elevation of total bilirubin value was observed in 2 cases in ondansetron group and 1 case in placebo group, however, these changes were mild and did not pose noteworthy clinical problem. From these results, ondansetron was shown to possess an excellent anti-emetic effect on nausea and emesis induced by highly emetogenic anti-cancer drugs, such as cisplatin, and to have no problem in safety, and thus it was considered to be a useful anti-emetic agent.

Adult