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Biomedical subjects

Y Ohashi

Publications and source records attributed to Y Ohashi.

At least 181 records · Page 10Linked to original sources
PubMed1999

Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer: a multicenter, randomized, controlled trial in Japan. Zoladex Study Group.

OBJECTIVE: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade. METHODS: Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate). RESULTS: There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone. CONCLUSIONS: Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

Aged↗
PubMed1999

Adjuvant therapy with oral fluoropyrimidines as main chemotherapeutic agents after curative resection for colorectal cancer: individual patient data meta-analysis of randomized trials.

BACKGROUND: Oral 5-fluorouracil and its prodrugs (tegafur, carmofur) is now being studied for adjuvant chemotherapy of curatively resected colorectal cancers. To evaluate the effect of these oral fluoropyrimidines (o-FPs), an individual patient data (IPD) meta-analysis of randomized clinical trials was performed in Japan as an inter-trialist group study. METHODS: Data from the three clinical trials in which postoperative adjuvant therapy with o-FPs was compared with surgery alone in patients with colorectal cancer were sought. IPD from a total of 4960 patients with follow-up periods of at least 5 years were analyzed. RESULTS: The results of the meta-analysis on an 'intention to treat' basis demonstrated a significant benefit of o-FPs in terms of the disease-free survival (DFS) of the total patients [risk ratio (RR) 0.830, 95% confidence interval (CI) 0.742-0.929, P = 0.001]. o-FPs were also demonstrated to be effective for survival in rectal cancer (RR 0.857, 95% CI 0.734-0.999, P = 0.049) and in Dukes'C colorectal cancer (RR 0.828, 95% CI 0.711-0.965, P = 0.016). CONCLUSION: The results suggest the advantage of long term o-FPs, possibly with the injection of mitomycin C, for prognosis for curatively resected colorectal cancer patients.

Administration, Oral↗
PubMed1999

Enhanced resistance to bacterial diseases of transgenic tobacco plants overexpressing sarcotoxin IA, a bactericidal peptide of insect.

Sarcotoxin IA is a bactericidal peptide of 39 amino acids found in the common flesh fly, Sarcophaga peregrina. Many agronomically important bacteria in Japan are killed by this peptide at sub-micro molar levels, and the growth of tobacco and rice suspension cultured cells is not inhibited with less than 25 microM. Transgenic tobacco plants which overexpress the peptide, i.e. over 250 pmol per gram of fresh leaf, under the control of a high expression constitutive promoter showed enhanced resistance to the pathogens for wild fire disease (Pseudomonas syringae pv. tabaci) and bacterial soft rot disease (Erwinia carotovora subsp. carotovora).

Animals↗
PubMed1999

Jasmonate-based wound signal transduction requires activation of WIPK, a tobacco mitogen-activated protein kinase.

A gene encoding a tobacco mitogen-activated protein kinase (WIPK) is transcriptionally activated in response to wounding. Transgenic tobacco plants, in which expression of endogenous wipk was suppressed, did not accumulate jasmonic acid or its methyl ester when wounded, suggesting that WIPK is involved in jasmonate-mediated wound signal transduction. Here, we demonstrate that activation of WIPK is required for triggering the jasmonate-mediated signal transduction cascade that occurs when wild-type tobacco plants are wounded. We also show that when plants are wounded, WIPK is rapidly and transiently activated, whereas the quantity of WIPK protein is maintained at a constant level. A transgenic tobacco plant in which the wipk gene was constitutively expressed at a high level showed constitutive enzymatic activation of WIPK and exhibited three- to fourfold higher levels of jasmonate than did its wild-type counterpart. This plant also showed constitutive accumulation of jasmonate-inducible proteinase inhibitor II transcripts. These results show that WIPK is activated in response to wounding, which subsequently causes an increase in jasmonate synthesis.

Cyclopentanes↗
PubMed1999

The lethal effect of a benzamide derivative, 3-methoxybenzamide, can be suppressed by mutations within a cell division gene, ftsZ, in Bacillus subtilis.

3-Methoxybenzamide (3-MBA), which is known to be an inhibitor of ADP-ribosyltransferase, inhibits cell division in Bacillus subtilis, leading to filamentation and eventually lysis of cells. Our genetic analysis of 3-MBA-resistant mutants indicated that the primary target of the drug is the cell division system involving FtsZ function during both vegetative growth and sporulation.

Bacillus subtilis↗
PubMed1999

Specific immunoglobulin E, interleukin-4, and soluble vascular cell adhesion molecule-1 in sera in patients with seasonal allergic rhinitis.

This study included 23 nonatopic volunteers and 84 patients with seasonal allergic rhinitis due to Japanese cedar pollen. Serum interleukin-4 (IL-4) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the patients were significantly higher than those in the nonatopic individuals, even outside of the pollen season. Both the good responders and the poor responders to antihistamine tablets showed significant increases in IL-4 and specific IgE during the pollen season, whereas such seasonal increases were not observed in the good responders to immunotherapy. Seasonal increases in IL-4 were significantly correlated with those of specific IgE. However, seasonal increases in sVCAM-1 were not significant. Seasonal increases in sVCAM-1 were not significantly different between the good responders and the poor responders to pharmacotherapy or immunotherapy. In conclusion, serum IL-4 and sVCAM-1 are increased in patients with seasonal allergic rhinitis, even outside of the pollen season; this finding might suggest underlying preponderant in vivo activation of T helper cell-2-like cells and inflammatory events in seasonal allergic rhinitis. A seasonal increase in IL-4 in sera might be at least partly involved in the seasonal increase in specific IgE in sera. Immunotherapy's inhibitory effect on IL-4 production and specific IgE response might be one of its working mechanisms.

Adult↗
PubMed1999

Decrease of serum levels of soluble CD23 during immunotherapy in patients with perennial allergic rhinitis.

There is increasing in vitro evidence that soluble CD23 (sCD23) is capable of potentiating the synthesis of human IgE and is likely involved in the expression of allergic diseases. Our study has aimed at investigating whether serum sCD23 is elevated in patients with perennial allergic rhinitis as compared to nonatopic controls, whether sCD23 in perennial allergic rhinitis fluctuates during the natural course in untreated patients, and whether sCD23 is decreased by immunotherapy. This study included 139 patients with perennial allergic rhinitis due to Dermatophagoides farinae who gave informed consent to participation. They were divided into 2 groups--an untreated group and an immunotherapy group--according to their treatment background. Thirty-one nonallergic, healthy volunteers were included to serve as controls. Symptom scores and serum concentrations of IgE specific to D. farinae and sCD23 were examined twice in each patient: at enrollment (first evaluation) and on a variant time course after enrollment (second evaluation). Serum concentrations of sCD23 were measured by a sandwich enzyme-linked immunosorbent assay. The level of sCD23 in patients with perennial allergic rhinitis was significantly higher than that in nonatopic controls (p < .0001). The level of sCD23 in perennial allergic rhinitis was correlated with the level of specific IgE against D. farinae. The sCD23 level did not fluctuate during the natural course for a span of 2.8 +/- 2.7 years in untreated patients (p = .1337), but was significantly decreased in patients who received immunotherapy for 2.7 +/- 2.2 years (p < .0001). The rate of decrease in sCD23 was significantly correlated with the rate of decrease in specific IgE (rs = .523, p < .0001) and symptom scores (rs = .450, p < .0001). In conclusion, the reduction in sCD23 during immunotherapy is probably related to the decrease in specific IgE and also plays a role in mediating its clinical effect.

Adult↗
PubMed1999

Phase I/II study of vinorelbine, mitomycin, and cisplatin for stage IIIB or IV non-small-cell lung cancer.

PURPOSE: To determine the maximum-tolerated doses (MTDs) of vinorelbine (VRB), mitomycin (MMC), and cisplatin (P), given in two courses every 28 days to previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: At least three or four patients were entered at each dose level. The starting dose was 20 mg/m(2) for VRB on days 1 and 8 and 4 mg/m(2) for MMC on day 1, with a fixed dose of P 80 mg/m(2) on day 1 every 4 weeks. MMC was increased to 6 mg/m(2) at dose level 2 and subsequently to 8 mg/m(2) at dose level 4. At dose level 3, VRB was increased to 25 mg/m(2). Twenty-five patients were entered onto the phase I study and 19 patients were entered onto phase II study. RESULTS: Nadir leukocyte and platelet counts decreased at each dose level. At dose levels 1 and 2, the dose-limiting toxicity (DLT) was not seen, but at dose levels 3 and 4, DLT was encountered in two patients. Nearly half the patients at dose level 4 had dose reduction due to grade 4 leukopenia. A mathematic model of all toxicity suggested that dose level 4 (VRB 25 mg/m(2) on days 1 and 8 and MMC 8 mg/m(2) and P 80 mg/m(2) on day 1, every 4 weeks) would be the recommended dose for phase II study at which grade 4 toxicity is expected in </= 25% of patients over two courses. Of the 25 assessable patients in the phase I study, 13 achieved a partial response and one had a complete response for a response rate of 56. 0%. Of the 19 assessable patients in the phase II study, 12 had a partial response (63.2%; 95% confidence interval, 38.4% to 83.7%). Grade 3 and 4 leukopenia was observed in 19 (100%), and grade 3 thrombocytopenia was seen in seven (36.8%). Median survival time was 10.7 months and the 1-year survival rate was 43.2% in the 44 assessable patients. CONCLUSION: The VRB/MMC/P regimen is effective against NSCLC, and its efficacy should be confirmed through a randomized study.

Adult↗
PubMed1999

[The critical appraisal of QOL questionnaire for prostate cancer patients].

BACKGROUND: Prostate cancer is a common malignancy that affects Japanese elderly men. Its incidence is increasing, recently, and its treatments are various. The measurement of quality of life (QOL) has become important for the evaluation of and selection of treatments. In Japan, however, there is no standard way of measuring QOL for prostate cancer patients, except the Japanese version of the EORTC QOL questionnaire for prostate cancer patients. We examined the validity and feasibility of this translated EORTC QOL questionnaire for prostate cancer patients. METHODS: Sixty-nine prostate cancer patients who were under treatment in 4 hospitals were selected for this study. We applied the content validity, the factorial validity which was analyzed by the oblique principal component cluster analysis, the internal consistency analyzed by the alpha coefficient of Cronbach, the convergent validity which was used GHQ, IPSS and PS as external measures, and the feasibility. RESULTS: This questionnaire showed good internal consistency, as the alpha coefficient was 0.61 to 0.90 in all domains, except for sex life, which was the lowest. This questionnaire was classified into 7 clusters by the oblique principal component cluster analysis. Consequently, the factorial validity was good, except for items regarding sex life. As domains correlate well with external measures except in sex life, the convergent validity was good. It was suggested that only two items were not acceptable in regard to the content validity and the feasibility, and that the translation into Japanese of 2 items was inadequate. CONCLUSIONS: Our study suggests that the Japanese version of the EORTC QOL questionnaire for prostate cancer patients demands improvement for the practical employment in clinical trials, as there is a problem of translation and feasibility.

Aged↗
PubMed1999

[Use of the multifocal electroretinogram to evaluate retinal function after pars plana vitrectomy for diabetic macular edema].

PURPOSE: Multifocal electroretinograms (multifocal ERGs) were performed to evaluate retinal function in patients with diabetic macular edema. MATERIALS & METHODS: Eight eyes of 5 patients underwent pars plana vitrectomy for diabetic macular edema. Multifocal ERGs, fundus examinations, and fluorescent angiographies were done both before and after the operation. RESULTS: Post-operative visual acuity was improved by two or more lines in 3 eyes. In multifocal ERGs, the amplitude of the positive wave (P1) from the macular area decreased transiently after surgery (p < 0.05), but it improved with the passage of time. The P1 amplitude from the peripheral area was decreased throughout the observation period of six months (p < 0.05). For both areas, the P1 latency was increased significantly (p < 0.05) at one month post-operatively, and then decreased. CONCLUSION: These findings are consistent with the possibility that the surgical method, especially removal of the posterior cortical vitreous, can cause retinal damage.

Diabetic Retinopathy↗
PubMed1999

[Clinical effect of idarubicin on malignant lymphoma].

The anti-tumor efficacy and safety of idarubicin (IDR) were investigated among patients in whom the standard therapy for malignant lymphoma had failed or who had suffered a recurrence. IDR was administered at a dose of 12 mg/m2 or 15 mg/m2 by a single i.v. bolus, and this dosage regimen was repeated every 3 weeks. Among total of 21 evaluable patients, there were 3 CRs and 1 PR, for an overall response rate of 19.0% (4/21). All patients who attained CR were cases which had recurred after receiving combination chemotherapy including doxorubicin. Adverse reactions were bone marrow suppression, including leucopenia (90.5%), neutropenia (95.2%), and thrombocytopenia (47.6%); gastrointestinal symptoms such as nausea/vomiting (42.9%) and stomatitis (9.5%); alopecia (23.8%) and fever (19.0%). These results indicate that IDR is effective against refractory malignant lymphoma.

Adult↗
PubMed1999

T-cell-mediated immune responses in alloepithelial rejection after murine keratoepithelioplasty.

PURPOSE: To evaluate the role of delayed-type hypersensitivity (DTH) and cytotoxic T-lymphocyte (CTL) responses on alloepithelial rejection in a murine keratoepithelioplasty model. METHODS: C3H/He mouse corneal lenticules were grafted around the limbus in BALB/c mice, and alloepithelial rejection was assessed by microscopic evaluation. The relation between rejection scores and DTH or CTL responses to donor antigens was assessed by Spearman correlation analysis. Suppression of DTH responses by induction of anterior chamber-associated immune deviation (ACAID) was used to evaluate the contribution of DTH responses to allograft rejection. CTL responses were evaluated by in vitro and in vivo depletion of CD4+ or CD8+ cells. RESULTS: DTH responses, which developed 2 weeks postoperatively, correlated significantly with rejection scores (correlation coefficient r = 0.55). ACAID induction by anterior chamber inoculation of C3H/He splenocytes significantly suppressed allospecific DTH responses and alloepithelial rejection. While allospecific CTL responses also developed 2 weeks postoperatively and increased by 4 weeks, CTL responses did not exhibit positive correlation with rejection scores (r = -0.36, P = 0.076). The CTL responses were mediated exclusively by CD8+ cells. Although in vivo depletion of CD8+ cells abolished the induction of CTL responses, it did not prevent allograft rejection. Immunohistochemistry showed infiltration of CD4+ and CD8+ cells into the alloepithelium. Positive staining for interferon gamma but not interleukin 4 further implicated the participation of a DTH response. CONCLUSIONS: Allograft rejection after keratoepithelioplasty appears to be mediated primarily by DTH responses, with CTL responses playing only a minor role perhaps in modifying the development of rejection.

Animals↗