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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 361 records · Page 20Linked to original sources
PubMed1996

Long-term results of short segmental syngeneic small intestinal transplantation: comparison of jejunal and ileal grafts.

A short-segment intestinal graft is favorable to reduce the rate of rejection and the incidence of graft-versus-host disease in recipients of small intestine transplantation. To determine whether a jejunal or an ileal graft is preferable with respect to intestinal morphology and function, syngeneic two-step small intestinal transplantations were performed using male Lewis rats (RT1(1)). They were divided into two groups according to the small intestine donor site (group 1 received 10 cm of jejunum; group 2 received 10 cm of ileum). There was no significant difference in the survival rate or weight gain between the two groups. Nearly all the hematologic findings, serum nutritional parameters, and results of liver function tests were normal for both groups. The only difference was that the serum total bile acid level was significantly higher in group 2. Fifty weeks after transplantation, the graft mucosa showed normal architecture, with adaptive hyperplasia of villi and crypt noted through histological study. The villus height of group 1 was 595 +/- 64 microns (control, 452 +/- 67 microns); that of group 2 was 732 +/- 53 microns (control, 217 +/- 20 microns). The crypt depth of group 1 was 228 +/- 35 microns (control, 165 +/- 24 microns); that of group 2 was 320 +/- 19 microns (control, 102 +/- 19 microns). These compensatory changes were more pronounced in group 2. The authors conclude that, on the basis of long-term functional capacity, there was no significant difference between jejunal and ileal grafts, and that both segments were suitable for transplantation. However, the ileal graft was considered to be better with respect to morphological adaptation.

Animal Nutritional Physiological Phenomena↗
PubMed1996

A late phase II study of RP56976 (docetaxel) in patients with advanced or recurrent breast cancer.

A late phase II clinical trial of RP56976 (docetaxel), derived from Taxus baccata was performed to evaluate anti-tumour activity, time to progression and clinical toxicity in patients with advanced or recurrent breast cancer. The patients, between 15 and 80 years old with performance status (PS) of 0-2, received at least two cycles of docetaxel 60 mg m-2 intravenously at 3-4 week intervals. Of the 81 patients enrolled, the 72 eligible for the study were given a total of 327 cycles, with a median of four cycles each. Five patients obtained a complete response (CR) and 27 a partial response (PR); the response rate (RR) was 44.4% (95% confidence interval 32.7-56.6%). A relatively high RR of 9/28 (32.1%) was observed in patients who had received prior chemotherapy involving anthracyclines. The dose-limiting toxicity was grade 3-4 leucocytopenia or neutropenia, found in 78.9% and 85.9% patients respectively. Other severe (grade > 3) toxicities included alopecia (38%), anorexia (18.3%), nausea/vomiting (11.3%), and fatigue (9.9%). Hypersensitivity reactions, oedema and skin toxicity were not severe and were reversible. One therapy-related death occurred 10 days after the initial dose was given. These findings indicate that docetaxel has potent activity against metastatic breast cancer, and that the dose of 60 mg m-2 is safe.

Adenocarcinoma↗
PubMed1996

Wortmannin and Li+ specifically inhibit clathrin-independent endocytic internalization of bulk fluid.

Incubation of a human fibrosarcoma cell line HT-1080 in Li(+)-containing medium inhibited internalization of a fluid marker, horseradish peroxidase (HRP), by more than 80%. The ion inhibited the activity enhanced by Ca2+ or phorbol 12-myristate 13-acetate. We also found that wortmannin (WT), a potent inhibitor of phosphoinositide (PI) 3-kinase (PI 3-k), inhibited the non-stimulated and the two stimulated types of endocytosis to the same extent as Li+. In contrast, neither WT nor Li+ influenced the early internalization of transferrin (Tfn), EGF or platelet-derived growth factor. Neither targeting to early endosomes nor recycling of the once-internalized Tfn was influenced. When the cytoplasmic pH was lowered by chasing cells that had been preincubated with 25 mM NH4Cl in an amiloride-containing Na(+)-free medium, more than 90% of internalization of Tfn in HT-1080 cells was inhibited, while that of HRP was reduced by only 35%. In contrast, WT reduced the uptake of HRP by KB cells by 34%, while 60% of the activity was inhibited by the treatment for cytoplasmic acidification. Comparison of other cells i.e., A-549 and a human diploid cell line Miyajima, indicated that cells showing higher sensitivity to WT were less sensitive to low cytoplasmic pH. These results suggest that, in all the cells studied, bulk fluid is internalized either via a clathrin-independent/PI 3-k-dependent route or via a clathrin-dependent/PI 3-k-independent one, though the ratio varied among them. We also found that internalization of a mAb directed toward the 116 (100)-kDa subunit of vacuolar ATPase [OSW2; Sato and Toyama (1994) J. Cell Biol. 127, 39-53] in the fluid phase was inhibited by WT, but the antibody was still internalized in a surface-bound form. Regardless of the treatment with WT, most of the antibody was transported to endosomes that were associated with Tfn receptor. These results suggest that both internalization routes are targeted to the same early endosomal compartments.

Ammonium Chloride↗
PubMed1996

[A fulminating case of Edwardsiella tarda septicemia with necrotizing fasciitis].

A 67-year-old Japanese male, suffering from liver cirrhosis with hepatoma, was admitted to the Yokohama National Hospital because of ascites retention. On physical examination, his abdomen was massively distended with ascites and his lower extremities were edematous. Laboratory findings on admission revealed hypoalbuminemia, moderate icterus, pancytopenia and hepatitis C virus antibody positivity. After admission, abdominal distention and edema were improved with the use of diuretics. On the 15th day of hospitalization, the patient noted diarrhea and bowel movements that occurred 10 times a day. On the following day, his body temperature rose to over 39 degrees C. On the morning of the 17th day, he complained of severe pain in the right lower extremity. Swelling and erythema over his right lower leg were evident. The skin lesion spread rapidly over the knee and became necrotic. His right leg became increasingly swollen with the development of edema and hemorrhagic bullae. About 4 hrs after the emergence of the skin lesion, his blood pressure fell to less than 60 mmHg. Laboratory findings suggested disseminated intravascular coagulation and multiple organ failure due to serious bacterial infection. In spite of vigorous treatment including administration of antibiotics, dopamine, gabexate mesilate and plasma, he did not recover from the state of shock and died about 14 hrs after the appearance of leg pain. Bacterial culture of the blood and contents of the bullae grew a gram negative rod identified as Edwardsiella tarda (E. tarda). Histological findings showed necrotizing fasciitis. E. tarda has recently become recognized as a pathogenic bacteria, particularly in patients with an underlying illness. This is the first reported case of E. tarda septicemia with necrotizing fasciitis.

Acute Disease↗
PubMed1996

Phase II trial of docetaxel in previously untreated advanced non-small-cell lung cancer: a Japanese cooperative study.

PURPOSE: This phase II study was conducted to evaluate the efficacy and toxicity of moderate-dose (60 mg/m2) docetaxel in Japanese patients with previously untreated advanced (stage IIIB or IV) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Docetaxel 60 mg/m2 was administered intravenously over 1 to 2 hours to patients with previously untreated stage IIIB or IV NSCLC. Treatment was repeated every 3 weeks. No routine premedication was given. The patients' median age was 67 years (range, 40 to 80). Forty-four patients (59%) had adenocarcinoma and 55 (73%) had stage IV disease. The median Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 1. RESULTS: Seventy-five patients were eligible and treated with docetaxel. Fourteen patients (19%) achieved a partial response (PR); response was not significantly affected by histology or clinical stage. The median survival time for all patients was 297 days. The predominant toxicity was neutropenia, with 87% of patients experiencing grade 3 or 4. Febrile neutropenia was seen in eight patients. Hypersensitivity and edema each occurred in only 4% of patients and were easily manageable. There was no possible treatment-related death of acute exacerbation of pneumonitis. CONCLUSION: Docetaxel 60 mg/m2 showed significant activity in advanced NSCLC, with a low incidence of hypersensitivity or peripheral edema. Further investigation of this agent in NSCLC is warranted, especially in combination with other active drugs.

Adenocarcinoma↗
PubMed1996

[LY188011 phase I study. Research Group of Gemcitabine (LY188011)].

LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.

Adult↗
PubMed1996

[Survival and changes of clinical laboratory data in phase II study with 5'-DFUR].

With patients registered in a Phase II study of 5'-DFUR, we analyzed the results of survival and laboratory findings. The 50% survival days in patients with gastric cancer included: 371 days in all evaluable patients; 912 days in patients of CR+PR; 484 days in MR+NC; and 158 days in PD. On the other hand, those in patients with colorectal cancer were: 467 days in all evaluable patients; 1,308 days (66.7% survival) in CR+PR; 586 days in MR+NC; and 276 days in PD. The figures in patients with breast cancer were: 1,761 days (58.5% survival) in all evaluable patients; 1,761 days (82.1% survival) in CR+PR; 878 days in MR+NC; and 546 days in PD. These 50% survivals were markedly longer than for other anti-cancer drugs given singly or in combination, although response rates with other drugs were higher than with 5'-DFUR. Laboratory findings in patients with gastric and colorectal cancers given 5'-DFUR disclosed many cases with improved levels of blood cells and liver function. There was a correlation between improved laboratory findings and survival. Furthermore, in animal experiments 5'-DFUR improves cancer cachexia. This is thought to be related to the improved survival and laboratory findings. We concluded that the prolonged survival observed in our study was related to reduction in cancer cachexia and improved laboratory findings.

Administration, Oral↗
PubMed1996

[Polyangiitis overlap syndrome with multiple pulmonary aneurysms and renal vascular hypertension].

A 37-year-old man with multiple nodules on a chest X-ray film, hypertension, and proteinuria was admitted to our hospital in September, 1993. Thirteen years earlier, he had been admitted to another hospital because of bloody sputum, fever, and dyspnea. He also had slight oral aphthae and slight iridocyclitis. A chest X-ray film at that time showed bilateral diffuse reticular shadows, and his illness was diagnosed as acute interstitial pneumonitis. Since that time, he had been continuously receiving tapering doses of prednisolone. His chest symptoms were relieved, and the findings on the chest X-ray film resolved with that treatment. In 1993, he also had positive tests for HBs antigen and for HLA-B51, and he was found to have renal vascular hypertension. Chest CT films and a pulmonary angiogram showed multiple aneurysms and occlusions of pulmonary arteries. A renal angiogram showed multiple intraparenchymal aneurysms of renal arteries. A specimen taken by open-lung biopsy showed healed endoarteritis obliterans of muscular arteries and no alveolitis. His illness was diagnosed as polyangiitis overlap syndrome, because of the unclassified systemic necrotizing vasculitis.

Adult↗
PubMed1996

[Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer].

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

Administration, Oral↗
PubMed1996

[A late phase II study of LY188011 (Gemcitabine hydrochloride) in patients with non-small-cell lung cancer. Gemcitabine Cooperative Study Group B for Late Phase II].

A late phase II study of LY188011 (gemcitabine hydrochloride), a new nucleoside derivative, in patients with non-small-cell lung cancer (NSCLC) was conducted at 24 Japanese institutions shown in Table 1 with a total of 69 patients enrolled. Of these, 67 were eligible and 64 completed at least one course of LY188011 therapy. The response rates (partial response only) in these populations were 20.9% (14/ 67) and 21.9% (14/64), respectively. Serious adverse reactions were septic shock and interstitial pneumonia in one patient each. Grade 3 or 4 adverse reactions included neutropenia (22.7%), decreased hemoglobin (13.4%), leukopenia (10.4%), anorexia (10.4%), malaise (7.5%), and nausea/vomiting (6.0%). Based on these results, it may be concluded that LY188011 has a high efficacy and benefit for the treatment of NSCLC.

Aged↗
PubMed1996

[Primary medical therapy (preoperative therapy) in the treatment of operable breast cancer].

Information from randomized and nonrandomized studies does indicate that preoperative chemotherapy (primary medical therapy) results in a high tumor response rate and an increase in the use of breast conservation, despite great variation in the chemotherapeutic regimens used. The findings reported by Powles et al in this issue of the Journal of clinical oncology clearly confirm. Fisher's group studies (NSABP-18) and those of others in that regard. Despite the repeated demonstration that a putative increase in breast-conserving surgery results as a consequence, the proper role of preoperative therapy in the management of primary breast cancer remains unclear. This uncertainty relates to the fact that no new paradigm has been formulated to govern the use of such therapy and to replace the two independent paradigms that currently govern the treatment of breast cancer. One of these paradigms relates to the eradication of local manifestations of the disease by surgery and radiation therapy; the other serves as the exemplar for eliminating disseminated disease by systemic therapy. The absence of a clear understanding of the clinical role of preoperative therapy does not negate the importance of continuing to conduct biologic and clinical investigations using that therapeutic strategy as a model. However, it is our content that, at this time, preoperative therapy should be limited to patients in randomized studies.

Antineoplastic Agents↗