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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 271 records · Page 15Linked to original sources
PubMed1998

Collagen synthesis by cultured cardiac fibroblasts obtained from cardiomyopathic hamsters.

The aim of the present study was to clarify myocardial collagen metabolism in cardiomyopathic hamsters and the effects of the angiotensin converting enzyme inhibitor, captopril, on collagen synthesis. Cardiac fibroblasts from Bio 14.6 cardiomyopathic hamsters and from non-cardiomyopathic Flb hamsters were cultured and used in the 4th passage. The synthetic activity of collagenous protein from the two types of hamsters was determined by measuring 3H-proline uptake, and the collagen type was subsequently analyzed by SDS-PAGE in cultured cardiac fibroblasts. Also studied were the effects of the angiotensin converting enzyme inhibitor captopril (1 microM) on collagen synthesis by cardiac fibroblasts from cardiomyopathic hamsters. Twenty five-week-old Bio 14.6 hamsters had significantly higher synthetic activity of collagenous protein and rate of collagen synthesis compared with 13-week-old Bio 14.6 hamsters or 25-week-old Flb hamsters [Bio 14.6(25-week); 12.4 +/- 1.6, Bio 14.6(13-week); 4.8 +/- 0.4, Flb (25-week); 8.7 +/- 0.9 cpm/cell, Bio 14.6(25-week); 11.0 +/- 0.9, Bio 14.6(13-week); 3.9 +/- 0.4, F1b (25-week); 4.8 +/- 0.4%, p < 0.05]. Qualitatively, 25-week-old Bio 14.6 hamsters had significantly higher synthetic activity of type I, III, IV and V collagens compared with 25-week-old F1b hamsters. The synthetic activity of type III collagen was increased the most in the cardiomyopathic group. Captopril (1 microM) caused a significant decrease in synthetic activity of collagenous protein in 25-week-old Bio 14.6 hamsters (12.4 +/- 1.6 cpm/cell-->10.9 +/- 1.1 cpm/cell, p < 0.05). Qualitatively, the synthetic activity of type III collagen was decreased to about half. Our study revealed enhanced collagen synthetic activity in cardiac fibroblasts from Bio 14.6 hamsters. Captopril improved collagen metabolism in cultured cardiac fibroblasts from Bio 14.6 hamsters not only quantitatively but also qualitatively. The mechanism of this improvement may be related to the cardiac renin angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Light and electron microscopic detection of anionic sites in the rat choroid plexus.

Electron microscopy of ultrathin sections stained with cationic iron colloid revealed that, in the choroid plexus of the rat brain ventricles, the luminal surface and fenestral diaphragm of the capillary endothelium as well as the basement membranes of the endothelium and epithelium are strongly anionic or intensely negatively charged. The iron colloid reaction to these anionic sites was erased by treatment with hyaluronidase or digestions with chondroitinase ABC/heparitinase/keratanase. These results indicate that sulfated proteoglycans provide such anionic sites of the choroidal capillaries. Discussion suggested that the negative charge on the luminal surface of the capillary endothelium prevents the adhesion of blood cells to capillary walls and also prevents endothelial adhesion by their repelling each other. It was further discussed that the negatively charged endothelial fenestrae and basement membranes may act as a charge barrier to inhibit the passage of anionic molecules.

Animals↗
PubMed1998

Chronic bromvalerylurea intoxication: dystonic posture and cerebellar ataxia due to nonsteroidal anti-inflammatory drug abuse.

Nalon-Ace and other nonsteroidal anti-inflammatory drugs (NSAID) containing bromvalerylurea (BVU) are sold as over-the-counter (OTC) drugs and are obtainable without prescription in Japan. A 32-year-old woman was diagnosed as having chronic BVU intoxication due to habitual use of Nalon-Ace. In addition to cerebellar ataxia and pyramidal signs well known in this condition, she showed an as yet non-described dystonic posture of the neck. Laboratory tests revealed an elevated concentration of serum organic bromide, iron deficiency anemia, and hyperchloremia. Brain magnetic resonance imaging (MRI) revealed definite cerebellar atrophy. We should consider the possibility of chronic BVU intoxication in peculiar neurological cases like ours.

Adult↗
PubMed1998

[An autopsy case of deep cerebral venous thrombosis: serial CT, MRI and pathological findings].

A 17-year-old girl developed vomiting of sudden onset, followed by a state of confusion that progressed rapidly to coma within one day. Laboratory tests indicated iron deficiency anemia and reactive thrombocytosis, but there was no evidence of coagulopathy. There was no history of medication including the contraceptive pill, either. Emergency CT scan without contrast enhancement showed increased density along the course of the vein of Galen and internal cerebral veins. A repeated CT scan without contrast enhancement carried out 24 hours after the onset of the illness confirmed extensive bilateral hypodensity of the thalami, basal ganglia and adjacent white matter. There was also a prominent spontaneous increase in the density of the deep cerebral venous system. MRI was performed 3 days after the onset of the illness, which showed absence of a flow void in the region of the internal cerebral veins and septal veins on T1-weighed images. T2-weighted images showed low intensity in these veins. At autopsy, the bilateral internal cerebral veins were occluded by fresh thrombosis and hemorrhagic infarction was seen in the bilateral thalami.

Adolescent↗
PubMed1998

[Adjuvant for breast cancer chemo-endocrine therapy].

Early detection and improved therapy together have reduced the mortality for breast cancer in the world. A paradox in the management of patients with breast cancer is the observation that the majority appear to be curable at the time of initial surgery, yet a large number later experience relapse followed by death from disease. To combat this problem, systemic drug therapy in conjunction with surgery and radiation therapy is now standard for many patient subgroups, although the specific decision to use hormonal therapy, combination chemotherapy, or both remains complex and controversial. Adjuvant therapy for breast cancer is an area in constant evolution. Randomized clinical trials are the critical step leading to the identification of improved therapies, that will become our new "standards" of management.

Antineoplastic Agents, Hormonal↗
PubMed1998

[Phase I study of orally administered UFT plus l-leucovorin].

A Phase I study of UFT plus l-LV was conducted in 29 patients (pts) with G.I. cancer on a multicenter cooperative study. UFT and l-LV were given orally in two divided doses for 28 consecutive days, followed by a 14 day-rest period. UFT was fixed in three doses, 250, 313 and 375 mg/m2/day, and l-LV was increased in dose from 25 to 50 and to 100 mg/body/days. Dose-limiting toxicities were anorexia, diarrhea, and nausea/vomiting. The maximum tolerated dose of UFT was 375 mg/m2/day, and l-LV 25 mg/body/day. Severe myelotoxicity was not observed. There were three responders (PR) out of 21 pts with measurable disease at UFT doses of 313 mg/m2/day and l-LV 50 and 100 mg/body/day. Responses observed were abdominal mass (rectal ca), liver metastasis (pancreas ca) and metastasis of liver and lymph-node (gastric ca). As a result of pharmacokinetics, plasma concentrations of 5-methyl-THF were maintained > 1.0 microM for over 5 hours that was considered to have a modulating effect on the plasma concentration. In doses of 50 mg and 100 mg/body/day of l-LV. No accumulations in plasma were observed in patient treated in 28 days by l-LV/UFT therapy. It was suggested UFT and l-LV did not interfere with each other's absorption. A Phase II study is recommended, with doses of 313 mg/m2/day of UFT and 50 or 100 mg/body/day of l-LV.

Administration, Oral↗
PubMed1998

[Phase I study of TAT-59 (a new antiestrogen) in breast cancer. TAT-59 Study Group].

Phase I study of TAT-59 (Miproxifen), an antiestrogen developed in Japan for breast cancer, was conducted with the collaboration of 12 hospitals. A single dose of 1.25, 5, 10, 20, 40 and 80 mg, or 5 consecutive daily doses of 1.25, 5, 10, 20 and 40 mg/day, were given orally. After single dosing, no clinical adverse effects were found. Decrease of serum Na, Cl, Ca level and increase of serum LDH level were observed in one patient after a single dose of 5 mg of TAT. An increase in the serum LDH level was also observed in one patient after a single dose in the of 10 mg of TAT. An increase in the serum LDH level and total bilirubin, increase of eosinophil, K and milky serum were also observed in one patient after a single dose of 40 mg of TAT, respectively. All of these abnormal values returned to the normal level within 26 days after final administration of TAT. No adverse clinical findings nor abnormal laboratory findings were observed after consecutive administration of TAT. After postprandial single dosing, the time to reach the maximum serum concentration (Tmax) of DP-TAT, dephosphorylated metabolite of TAT, and its demethylated metabolite, DMDP, ranged from 5.0 to 7.3 hr and from 17.0 to 42.8 hr, respectively. The maximum serum concentration (Cmax) and AUC of DP and DMDP elevated in a dose-dependent manner. T1/2 of DP and DMDP ranged from 24.2 to 41.5, and from 91.9 to 214.7 hr, respectively. There were no significant differences between pharmacokinetics of TAT before and after food intake. Based on the above results, we concluded that a Phase II study should be conducted to evaluate the efficacy, safety and optimal dose of TAT.

Administration, Oral↗
PubMed1998

[A cooperative study on concomitant with low-dose divided administration of cisplatin (CDDP) and sustained drip infusion of 5-fluorouracil (5-FU) for unresectable advanced gastric cancer. Osaka Cisplatin Gastric Cancer Study Group].

For patients with unresectable gastric cancer registered between July 1994 and September 1995, the following dosage regimen was examined: a drip infusion of cisplatin (CDDP) at 7 mg/m2/day for 5 consecutive days and 2-day withdrawal a week for 3 weeks with concomitant sustained drip infusion of 5-FU at 300 mg/m2/day for 21 days. The whole cycle was repeated again after 2-week withdrawal. The antitumor effect was seen in 39.4% among 33 cases. With respect to histological classification, there was no difference in appearance of the effect between the moderately differentiated type at 62.5% and the low-differentiated type at 42.9%. The cases which became resectable after the administration included those in which the tumor disappeared completely in the resected specimens. As adverse reactions encountered in the cases above Grade 3, anorexia, nausea and vomiting and diarrhea were seen as clinical symptoms in 10, 5.3 and 11.8%, respectively. As laboratory test values, decrease in hemoglobin, leukocytopenia and thrombocytopenia were seen in 16.7, 15.8 and 5%, respectively, while renal or liver dysfunction did not occur. This dosage regimen was considered useful for unresectable advanced gastric cancer, although myelosuppression should be watched carefully.

Adult↗
PubMed1998

[An early phase II clinical study of S-1 in patients with breast cancer. S-1 Cooperative Study Group (Breast Cancer Working Group)].

An early phase II clinical study of S-1 in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group (Breast Cancer Working Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg (dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty-eight patients were enrolled, 27 were eligible for the study, and 25 were evaluable for efficacy. Four complete responses and seven partial responses were obtained, and the response rate was 40.7% (11/27) [ninety percent confidence interval for this response was 26.7-56.4%]. The major adverse reactions observed were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7% (11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia 55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The results suggested that the efficacy and safety of S-1 were effective against advanced or recurrent breast cancer. The objective of study judged should be investigated in a late phase II clinical study.

Adult↗
PubMed1998

[Characteristics of screening-detected breast cancer and trends in its therapy].

Recently breast cancer has become one of the most common malignancies and one of the major causes of cancer death in Japan. In order to detect earlier stage breast cancer and to stop the increasing mortality, there is a greater need for mass screening. Mass screening performed by physical examination has a history of about thirty years in Japan, but it has had no effect in reducing breast cancer mortality. A new modality, mammography, is effective to detect non-palpable lesions, so it is expected to improve the accuracy of screening and reduce the mortality of breast cancer. Randomized trials in western countries have demonstrated that screening with mammography is effective for breast cancers in women aged 50 -69. In Japan, limited studies reported that effectiveness of screening was improved when mammography was combined with physical examination for detecting early breast cancer, but it is still unknown whether screening reduces breast cancer mortality. Since indications of breast conservation therapy have been rapidly extended it follows that breast conservation surgery for screening-detected cancer has increased. In Japan, because of its medical system, it seems impossible to conduct randomized trials for evaluating the efficacy of screening. Thus, it is important to interpret the screening data in western countries and to compare data with those from screening trials of Japan in the future.

Adult↗
PubMed1998

[Phase I clinical study of oxaliplatin].

Oxaliplatin is a new platinum derivative. A multicentric phase I study was conducted with a monotherapy of Oxaliplatin. A total of 20 patients were enrolled who had histologically proven 6 ovarian cancers, 5 uterine cervix cancers, 3 lung cancers, 3 breast cancers, 1 endometrial cancer, 1 gastric cancer, and 1 colorectal cancer. Oxaliplatin was administered as a 2-hour infusion at doses of 20, 40, 80, 130, and 180 mg/m2 every 3 weeks, for a total of 30 cycles. A dose-related and reversible peripheral sensory neuropathy was the dose-limiting toxicity with minimal hematotoxicity and no nephrotoxicity. No hydration was needed. The plasma platinum concentration was biphasically decreased. Cmax and AUC were dose-dependent. T1/2 beta was 31.3 hours. The recommended dose for further studies was 130 mg/m2. A partial response was observed in endometrial cancer.

Adult↗
PubMed1998

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent gastric cancer: a Japanese Cooperative Study Group trial (group A)].

A late phase II clinical study of RP56976 (docetaxel) was conducted in patients with advanced/recurrent gastric cancer as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of the 76 patients enrolled, 66 patients were eligible and 59 patients were evaluable for response. One patient showed complete response (CR), 13 patients partial response (PR), 1 patient minor response (MR), 19 patients no change (NC) and 25 patients had progressive disease (PD). The overall response rate in 59 evaluable patients was 23.7% (95% CI = 13.6-36.6%). The primary tumor showed a 4.3% (1/23) response, while the metastatic lesions in the abdomen, pelvic mass, lung, liver, and lymph nodes showed response rates of 62.5% (5/8), 33.3% (1/3), 33.3% (1/3), 14.8% (4/27), and 13.9% (5/26), respectively. About hematological toxicity, severe (Grade 3 or more) leukopenia was observed in 36 patients (56.3%) and neutropenia in 52 patients (81.3%). Other major toxicity (Grade 3 or more) included nausea/vomiting in 11 patients (17.2%), anorexia in 9 patients (14.1%), fatigue in 5 patients (7.8%), and alopecia in 7 patients (10.9%), all which were tolerable. The results show that docetaxel is an effective anticancer agent for advanced/recurrent gastric cancer.

Adult↗
PubMed1998

[Phase I study of raltitrexed (ZD-1694)].

A multicenter cooperative phase I study of ZD-1694 (raltitrexed), a novel, folate-based thymidylate synthase (TS) inhibitor, was conducted with single and repeated doses in 30 patients with various malignant tumors. ZD-1694 was intravenously infused over 15 minutes. In the single-dose study, the initial dose was fixed at 1.0 mg/m2 (1n), and the dose was escalated stepwise up to 3.5 mg/m2 (3.5 n). Based on the results of the single-dose study, in the repeated-dose study, doses of 2.5 n and 3 n were infused every three weeks (3 weeks/one course). In principle, patients received 2 courses or more. Of the 29 eligible patients, 16 were in the single-dose study and 13 in the repeated-dose study. Adverse reactions were evaluated in all eligible patients. In the single-dose study, neutropenia, nausea/vomiting, diarrhea, and transaminase (GOT, GPT) increases, of grade 3 or higher, occurred at high doses of 3 n and 3.5 n. These were regarded as dose-limiting toxicities (DLT). DLT of grade 3 or higher were observed in 1 of 4 patients given 3 n and 2 of 4 patients given 3.5 n. These results suggested that the maximum tolerated dose (MTD) of ZD-1694 was 3.5 n (3.5 mg/m2). In the repeated-dose study, DLT of grade 3 or higher was observed in no more than one third of each dose group, 2 of the 6 patients given 2.5 n and 2 of the 7 patients given 3 n. These results suggested that 3 n (3.0 mg/m2), a dose nearer to MTD, was the recommended dose for the phase II study. Although transaminase increases were observed in all patients, in 12 of them the increase was grade 2 or lower and reversible. A pharmacokinetic investigation showed the mean elimination half life of ZD-1694 plasma concentration was 91.5 hours in the single-dose group and 119.1 hours in the repeated dose group. It was suggested that ZD-1694 is metabolized to polyglutamates after uptake and retained in the cells for a long duration. However, no accumulation was seen in plasma concentration of ZD-1694 following repeated doses at 3-weekly intervals. One PR was observed in a patient with colorectal cancer receiving 2.5 n in the repeated-dose study. Based on these results, the recommended dosage and administration for the phase II study of ZD-1694 was 3 n (3.0 mg/m2) intravenously infused over 15 minutes every 3 weeks.

Adult↗
PubMed1998

Immunolocalization of collagen and collagen-binding heat shock protein 47 in fibrotic lung diseases.

Pulmonary fibrosis resulting from increased accumulation of various extracellular matrices is a prominent feature in chronic progressive lung diseases. Heat shock protein 47 (HSP47) is a collagen-binding stress protein known to have a specific role in the intracellular processing of procollagen molecules as a collagen-specific molecular chaperone in various organs. Possible involvement, however, of HSP47 in relation to increased deposition of collagens in fibrotic lung diseases is not yet known. In this study, we investigated the expression of HSP47 in various pulmonary fibrotic diseases. Formalin-fixed, paraffin-embedded lung sections from 17 autopsies of patients with various pulmonary fibrotic diseases, e.g., organizing pneumonia, interstitial pneumonia, idiopathic pulmonary fibrosis, and diffuse alveolar damage, were stained with monoclonal antibodies for alpha-smooth muscle actin, vimentin, CD68, Type III collagen, and HSP47. The extent of staining was graded semiquantitatively. Five control lung sections were also simultaneously studied. The fibrotic lung sections, in comparison with the control sections, had more interstitial cells positive for alpha-smooth muscle actin and fibroblasts positive for vimentin; we also saw increased infiltration of CD68-positive macrophages. For HSP47, in comparison with the control lung sections, markedly increased immunostaining was always noted in the fibrotic lung sections in association with increased accumulation of Type III collagen in the fibrotic masses. By double immunostaining, colocalization of collagens and HSP47 was noted in the regions of pulmonary fibrosis, and HSP47-expressing cells were found to be mainly alpha-smooth muscle actin-positive interstitial cells. From the above observations, we concluded that overexpression of HSP47 might play an important role in the excessive assembly/synthesis of collagens and could thereby contribute to the fibrosis found in pulmonary fibrotic lung diseases.

Actins↗
PubMed1997

Immunohistochemical Detection of P-glycoprotein in Breast Cancer and Its Significance as a Prognostic Factor.

Overexpression of P-glycoprotein (Pgp) in tumors is one of the major mechanisms which mediates the multidrug resistance (MDR) phenotype. To evaluate the prognostic significance of Pgp in breast cancer, Pgp expression was examined in paraffin-embedded tissue sections of 94 breast cancer specimens by immunohistochemistry. Tissue specimens were obtained by mastectomy without preoperative chemotherapy. UIC2 monoclonal antibody which recognizes an extracellular epitope of human Pgp was employed. Of the 94 breast cancer specimens, 35(37.2%)were positive for Pgp expression. Pgp expression had no correlation with menopausal or hormone receptor status, axillary Iymph node involvement or tumor size. However, a significant correlation was observed between Pgp expression and disease relapse (p=0.0322). Pgp-positive patients showed a significantly shorter disease-free survival period than Pgp-negative patients by the Kaplan-Meier method (p=0.0433). These results suggest that immunohistochemical detection of Pgp in breast cancer tissue may have prognostic value after radical operation.

Journal Article↗
PubMed1997

The Clinical Utility of Docetaxel in Adriamycin-Resistant Breast Cancer.

Taxanes were developed as third-generation anticancer agents following methotrexate and adriamycin, two major chemotherapeutic agents for breast cancer. These agents have been studied to confirm antitumor effects in anthracycline-resistant patients and patients with liver metastasis. In this study, we examined the usefulness of taxanes, especially docetaxel, in chemotherapy for breast cancer by reviewing results in Japan and other countries. In a late phase II clinical study in Japan, the administration of 60 mg/m(2) /hr/3-4w of docetaxel (DOC) reduced tumor size in 50.4% of patients. In 6% of these patients, complete response (CR) was achieved. The duration of response was 14.7 weeks. Thirty-five percent of 26 primary adriamycin(ADM)-resistant patients responded to DOC treatment (CR:4.0%).

Journal Article↗
PubMed1997

Changes in fidelity levels of DNA polymerases alpha-1, alpha-2, and beta during ageing in rats.

DNA polymerases (deoxynucleoside-triphosphate:DNA deoxynucleotidyltransferase EC 2.7.7.7.) were extracted from the regenerating livers of rats of various ages. The extracts were separated into three DNA polymerase fractions (alpha-1, alpha-2, and beta) by phosphocellulose column chromatography, and their fidelity levels were then monitored with the synthetic template-primer, poly (dA-dT), poly dA-dT10, or poly dC-poly dG. The fidelity levels of the three DNA polymerases from regenerating liver of rats younger than 20 months were high, while those of DNA polymerases from rats older than 20 months were significantly lower with similar profiles on all three template-primers. On the other hand, the fidelity levels of enzymes from 23- and 26-month-old rats were similar. These results indicate that the levels of error-prone DNA polymerases increase rapidly in the regenerating liver of rats from ages 20 to 23 months. This may due to the amplification of DNA polymerase gene mutations by an error-prone enzyme itself. However, the cells in which mutations in the functional gene occur may undergo cell death because the fidelity levels of the DNA polymerases in the older animals did not increase.

Aging↗