Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 613 records · Page 34Linked to original sources

PubMed1991

Clinical outcome of postoperative adjuvant immunochemotherapy with sizofiran for patients with resectable gastric cancer: a randomised controlled study.

Adjuvant immunochemotherapy using the antitumour polysaccharide sizofiran (SPG), an extract from the culture broth of Schizophyllum commune Fries, was prescribed randomly for 386 Japanese patients with resectable gastric cancer. Although the overall survival probability for 5 years did not differ between the SPG and control groups, in 264 patients with curatively resected cancer, the probability to 5 year survival and to recurrence in the sizofiran-administered patients was better than in the controls. In the multivariate analysis, four of six prognostic factors correlated with the prognosis of the 264 patients who underwent curative surgery, that is, nodal involvement (chi 2 = 21.426, P = less than 0.0001), age distribution (chi 2 = 9.262, P = 0.010), sizofiran administration (chi 2 = 6.507, P = 0.011), and primary tumour size (chi 2 = 9.345, P = 0.025). Thus, patients with a curatively resected gastric cancer had a better prognosis when sizofiran was prescribed in combination with antitumour drugs.

Adjuvants, Immunologic↗

PubMed1991

Regulation of mucosal responses by CD4+ T lymphocytes: effects of anti-L3T4 treatment on the gastrointestinal immune system.

The role of CD4+ T cells in the gastrointestinal (GI) immune system in vivo was studied in mice selectively depleted of this subset by treatment with monoclonal anti-L3T4 (GK1.5) mAb. Treatment of young BALB/c mice with weekly injections of anti-L3T4 mAb resulted in a selective depletion of CD4+ T cells in both IgA effector (lamina propria regions of the intestine; LP) and inductive (Peyer's patch; PP) sites. However, levels of CD3+CD4-CD8+ and CD4-CD8- (double negative) T cells remained constant or increased. When sections of small intestine were assessed for the isotype of Ig-containing cells, normal mice contained predominantly IgA plasma cells with small numbers of IgM and IgG plasma cells while anti-L3T4 treatment dramatically reduced the numbers of IgA plasma cells. When numbers of IgA-producing cells were assessed by the isotype-specific ELISPOT assay, the LPL of anti-L3T4 mAb-treated mice showed an 80% reduction in the number of IgA spot-forming cells. The effect of anti-L3T4 mAb treatment on IgA inductive sites was also studied and this treatment reduced the overall size of PP as well as the germinal centers in this tissue. Although anti-L3T4 treatment depleted CD3+CD4+ T cells in PP, the relative frequency of surface IgA-positive (slgA+) B cells in this tissue did not change. These results show that repeated injection of anti-L3T4 mAb results in a CD4+ T cell deficiency in both IgA inductive (PP) and effector (LP) sites. The depletion of CD4+ T cells resulted in reductions in the numbers of mature IgA plasma cells present in the LP of gut-associated tissues, and reduced the overall size of PP including germinal centers, but did not affect the frequency of sIgA+ B cells in this IgA inductive site.

Animals↗

PubMed1991

Carcinoma of the colon in children: a case report and review of 41 Japanese cases.

We report a case of sigmoid colon carcinoma in a 14-year-old girl. She had been suffering from several nonspecific abdominal symptoms for about 1 year before a definite diagnosis was made. While undergoing an operation, the main tumor was found to be unresectable. She died of Candida-induced septicemia on the 26th day after the operation. There have been 40 cases of colon carcinoma reported in the Japanese literature in patients 15 years of age or younger. We reviewed the 40 Japanese cases along with our case, and compared these to other children and adult studies. The prognosis is quite unfavorable in children because of the poor histological character and the delayed diagnosis. Serum carcinoembryonic antigen measurement might be one means for early diagnosis.

Adolescent↗

PubMed1991

Therapeutic effects of bovine enterovirus infection on rabbits with experimentally induced adult T cell leukaemia.

A bovine enterovirus, MZ-468, showed cytopathic effects on cell line F-647a, which was established by coculture of human T cell lymphotropic virus type 1-transformed MT-2 cells and X-irradiated rabbit lymphocytes. Microcalorimetric assay showed that residual, viable, MZ-468-infected F-647a cells produced less heat than non-infected cells. The therapeutic effects of MZ-468 infection were examined in rabbits in which adult T cell-like leukaemia (ATL) had been induced by inoculation of F-647a cells (1 x 10(8) cells). Six newborn rabbits were separated into three groups: group A was inoculated with F-647a cells only; group B was treated with MZ-468 at the time of inoculation with cells; group C was treated with the same amount of virus 24 h after the inoculation with cells and then once every 4 days. Both of the animals in group A and one in group C died 10 and 11 days, and 22 days, respectively, after the inoculation with cells. Both rabbits in group B and one in group C survived for more than 4 months. The rabbits that died were examined pathologically; leukaemic infiltrations were found in the lungs of the group B rabbits, and in the lungs, spleens and livers of both group A rabbits. Two identical experiments produced almost the same findings. These results suggest that bovine enterovirus might be used clinically to prolong the life-span of ATL patients.

Animals↗

PubMed1991

The effect of mass screening for breast cancer: results of a multivariate analysis.

To evaluate the life-prolonging effect of mass screening for breast cancer, we compared the risk of death for the patients detected by mass screening with that for the patients diagnosed in out-patient clinics, after adjusting for other relevant factors simultaneously by using the Cox regression model. A multivariate analysis using the Cox regression model in which clinical staging of disease was taken as one of the independent variables, showed that the risk of death for patients detected by mass screening was smaller by 0.765 times than that for patients found in out-patient clinics although the reduction was not statistically significant. This small reduction might be partly due to the effect of mass screening through early detection even within the same stage, and partly due to length bias, lead time bias and self-selection bias. When clinical staging of disease was removed from the independent variables, the risk of death for patients detected by mass screening was reduced from 0.765 times to 0.677 times that for patients diagnosed in out-patient clinics, which was statistically significant (P greater than 0.01). For asymptomatic patients detected by mass screening, such as reduction of the risk of death was from 0.789 times to 0.555 times that for patients found in out-patient clinics (P less than 0.05). These results suggest that mass screening for breast cancer may contribute to the reduction of the risk of death, although the effect of biases inherent in periodic screening was not removed completely in the present analysis.

Breast Neoplasms↗

PubMed1991

SAT, a 'new' low frequency blood group antigen, which may be associated with two different MNS variants.

A new private blood group antigen, SAT, was identified in an NFLD-Japanese woman as a result of testing 10,480 blood donors with a serum containing anti-NFLD and anti-SAT. Three other sera were subsequently also shown to contain anti-SAT. The donor's family showed that SAT is inherited as a dominant character and may be associated with a weak M antigen. Serological and immunochemical analysis revealed no other aberrations in the MNS system. Study of a second SAT+Japanese blood donor and his family suggested that SAT is associated with an unusual MNS variant resulting from a hybrid glycophorin comprising the N-terminus of glycophorin A and the C-terminus of glycophorin B. The propositus appears to be homozygous for the gene that produces the putative hybrid, which differs from previously described glycophorin (A-B) hybrids by expressing no S, s or U antigen. SAT antigen, therefore, may be associated with two different MNS variants in the only two families in which it has been identified.

Animals↗

PubMed1991

Metallothionein messenger RNA levels in the macular mutant mouse: an animal model of Menkes' kinky-hair disease.

Levels of metallothionein-1 (MT-1) messenger RNA (mRNA) in various tissues from normal and macular mutant mice at different stages of development (17 days of gestation, 1-, 3-, 7- and 14-day-old) were determined by Northern blot analysis. Renal MT-1 mRNA levels in mutant mice were slightly elevated at 3 stages compared to normal mice, with the exception of mutant fetus and 3-day-old mutant mice. Intestinal MT-1 mRNA levels in mutant mice were elevated at 3 stages compared to normal mice with the exception of mutant fetus and 3-day-old mutant mice. Hepatic MT-1 mRNA levels in mutant fetus and 1-day-old mutant mice were approximately the same compared to normal mice. In 3- and 7-day-old mutant mice, hepatic MT-1 mRNA levels were depressed and in 14-day-old mutant mice, they were increased compared to normal mice. Brain MT-1 mRNA could not be detected in normal and mutant mice at the 4 stages with the exception of 14-day-old mice. MT-1 mRNA in 14-day-old mice was detected and the level of that in mutant mice was slightly elevated compared to normal mice. After injection of Cu, MT-1 mRNA levels in kidney, liver and intestine were determined. The injection of Cu increased the level of MT-1 mRNA in the tissues of normal and mutant mice compared to control (saline-injected) mice. Significant differences in MT-1 mRNA levels in the tissues of both Cu-injected mice were not observed.

Animals↗

PubMed1991

The opioid activity and receptor selectivity of fluorinated Leu5 enkephalin analogues in vitro and in vivo.

The opioid activity and the selectivity for opioid receptor (subtypes) of newly synthesized fluorinated enkephalin (Enk) analogues, [2R, 4R], [2R, 4S], [2S, 4S] and [2S, 4R] trifluoro-Leu5-Enk (KKF-31, 32, 33 and 34) were investigated. The inhibitory effect of KKF-compounds on the electrically induced contractions of guinea-pig ileum (GPI) and mouse vas deferens (MVD) were dose-dependent but relatively lower than that of L-Leu5-Enk, except that KKF-34 was rather slightly more potent than L-Leu5-Enk in MVD preparations. In GPI preparations, the pA2 values of naloxone for these compounds were higher than those of naltrindole while the values of naltrindole for KKF-compound were higher than those of naloxone in MVD preparations. Intracerebroventricular KKF-31 and KKF-32 at doses of 20 and 10 nmol/mouse, respectively, produced analgesia comparable to 0.1 nmol Tyr-D-Arg-Phe-Lys-NH2 and 100 nmol Tyr-D-Thr-Gly-Phe-Leu-Thr; however, neither KKF-33 nor 34 produced analgesia up to the doses of 100 nmol/mouse. Both naloxone, 1 mg/kg, i.p., and naltrindole, 10 mg/kg, i.p., antagonized KKF-31- and KKF-32-induced analgesia. The results suggest that the introduction of trifluoromethyl group in Leu5 results in the alternation of the opioid activity and receptor selectivity. Although KKF-33 and KKF-34 possessed a more potent in vitro inhibitory effect than KKF-31 and KKF-32, mediated through mu- and delta-opioid receptors in both preparations, they did not show any appreciable analgesic effect. KKF-31 and KKF-32 produce naloxone- and naltrindole-reversible analgesia irrespective of in vitro mu- and delta-opioid activity.

Analgesics↗

PubMed1991

Electrocardiographically and symptomatically silent myocardial ischemia during exercise testing.

Certain patients with coronary artery disease (CAD) may have neither ST depression nor chest pain during exercise despite the presence of myocardial ischemia. The frequency and characteristics of such electrocardiographically and symptomatically silent ischemia were studied in 171 patients with both angiographically documented CAD and scintigraphically documented ischemia. Fifty-six (33%) of 171 patients had neither ST depression nor chest pain (Group N), and 115 (67%) had ST depression and/or chest pain (Group P). The two groups were similar with respect to age, gender, the prevalence of prior infarction, and peak systolic blood pressure. Group N patients, however, had a higher mean peak heart rate and rate-pressure product, less severe scintigraphic ischemia, a lower lung thallium-201 uptake, and a smaller number of diseased vessels. Stepwise discriminant analysis showed a history of effort angina, lung thallium-201 uptake, and scintigraphic severity of ischemia to be significant discriminators between Groups N and P. In conclusion, electrocardiographically and symptomatically silent ischemia may be common during exercise in patients with CAD, and less severe ischemia may be one of important determinants.

Coronary Angiography↗

PubMed1991

Time course of changes in brain energy metabolism of the rat after microsphere-induced cerebral embolism.

The present study was designed to elucidate pathophysiological changes in the brain energy metabolism after cerebral ischemia. Cerebral ischemia was induced in rats by administering microspheres into the right carotid canal, and the time course of changes in cerebral energy metabolism was examined up to the 7th day after the operation. Approximately 50% of the operated rats revealed typical symptoms of stroke. In the right hemisphere, cerebral ATP and creatine phosphate of the rat on the 1st to 7th day were greatly reduced by the microsphere-induced cerebral embolism (maximally 52 and 61%, respectively), whereas the tissue lactate level was increased on the 1st, 3rd and 5th day after the embolism (maximally 125%), suggesting an induction of microsphere-induced cerebral ischemia. These changes in the tissue metabolites were accompanied by a decrease in the mitochondrial oxidative phosphorylation measured in the presence of succinate. A similar trend in the changes of biochemical markers was observed in the left hemisphere, but to a lesser degree or to an insignificant degree. The pathophysiological alterations in behavior and cerebral metabolism of microsphere-injected rats tended to return toward the normal levels on the 7th day after the operation. The results provided information on a useful model for therapeutic studies of anti-ischemic agents in the brain.

Adenosine Triphosphate↗

PubMed1991

[DNA topoisomerase inhibitor as chemotherapeutic drug--clinical point of view].

CPT-11 is a semisynthesized derivative of camptothecin that has a potent antitumor activity by inhibiting DNA topoisomerase I. Leukopenia (mainly neutropenia) is DLF (dose limiting factor) and MTD (maximum tolerated dose) is higher than 250 mg/m2 in CPT-11 from the results of clinical phase I study. Now we are going on phase II study of CPT-11. We are seeing the cases responded to the drug in cancer of the lung, ovary, uterus, stomach, colorectum, pancreas, breast, malignant lymphoma etc.

Animals↗

PubMed1991

[Phase I study of YM881 (zinostatin stimalamer) suspension by hepatic arterial infusion. Research Group for Intra-arterial Infusion Therapy with YM881].

A phase I study of YM-881 (zinostatin stimalamer), neocarzinostatin combined with butylesterified styrene maleate, suspended in iodized poppy oil ethyl ester, was conducted in patients with hepatocellular carcinoma by giving single intra-arterial infusions via catheters inserted by Seldinger's method. Four dose levels, 2, 4, 6, and 8 mg, were tested. Major adverse reactions were fever, anorexia, nausea, vomiting, and abnormal hepatic function. Both the incidence and severity of adverse reactions tended to increase with the 8 mg dose. Tumor regression of 50% or more occurred in one receiving 2 mg and one receiving 4 mg. The results of the study suggest that doses of 6 mg or less may be appropriate for the phase II studies.

Adult↗

PubMed1991

[New interesting chemotherapeutic regimens in advanced gastric cancer].

We have made over view of new chemotherapeutic regimen for treatment of advanced gastric cancer 5-FU + MMC, FT + MMC and UFT + MMC therapy have been used widely for treatment of advanced gastric cancer as chemotherapeutic regimens in Japan. These regimens did not shown made than 25% in response rate as antitumor effect. Since development of CDDP, FP (5-FU + CDDP), FAP (5-FU + ADM + CDDP) and EAP (Etoposide + ADM + CDDP) is becoming gradually very important regimen for treatment of advanced stomach cancer patients. Recently, we have studied EAP therapy on 50 cases of advanced gastric cancer from January 1988 to September 1989. ADM 20 mg/m2, CDDP 40 mg/m2 and Etoposide 100 mg/m2 were administered on day 1 and 7, 2 and 8, and 4, 5 and 6, respectively, with not less than 2 courses every 3 to 4 weeks. The rate of effectiveness were obtained 43.8% with a confidence interval 95% of 30-58%. Median survival time was only 5.1 months for EAP therapy, which was highly effective but led to no prolonged survival period. Thus it is thought that good control of leukopenia, a dose-limiting factor remains to be examined. Biochemical modulation of 5-FU using such as MTX + LV and CDDP + LV (leucovorin) now under studying in the nation wide in Japan, so far it is getting better results.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

[Early changes of postpneumonectomy lung growth in premature rats].

Following pneumonectomy in animals, the contralateral lung increases in volume, weight, collagen content, protein, and cell number, reaching levels approximate to those of both lungs of control animals. The volume and weight response in quicker and more complete in young animals compared to old animals. The increase in the amount of DNA was found to be greater in young rats compared to old ones. However, little is known about the effects of pneumonectomy in immature animals, in which combined effects of normal and the compensatory lung growth may be expected. The present studies were aimed at elucidating early changes in terms of morphology and biochemistry in the contralateral lung following pneumonectomy in premature rats. Male Sprague-Dawley rats (2 week-old) were subdivided into 3 groups. Group P, underwent left pneumonectomy, group S was sham operated, which group C was matched by age, sex, and weight with group P. Morphological studies consisted of light microscopic morphometry and immunohistochemistry using anti-bromodeoxyuridine (BrdU) were performed. Biochemical studies included measurement of DNA polymerase activity, DNA and RNA content, collagen and elastin content. The wet lung weight in group P after one week reached approximately the same as that of bilateral lungs of groups S and C. The fixed lung volume of group P reached that of group S or group C at three weeks. The activity of DNA polymerase and BrdU positive alveoli were increased only during the early period following pneumonectomy. DNA content in group P reached the same range as group S and C at 4 weeks, suggesting the occurrence of cellular hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

[Phase II study of YM881 (zinostatin stimalamer) suspension injected into the hepatic artery. Research Group for Intra-arterial Injection Therapy with YM881].

A phase II study of YM 881 (zinostatin stimalamer) to determine the response and safety was conducted in patients with hepatocellular carcinoma by injecting a suspension of the drug into the hepatic artery. Repeated doses of 4 to 6 mg of the drug were given every 4 weeks so that the tumor tissues were filled with the suspension. Of the 195 registered patients, 15 were ineligible for the study, 8 dropped out, and data were missing for 5. A total of 167 patients completed the study. Response was assessed in the 167 patients who completed the study. CR was found in one, PR in 59, MR in 25, NC in 67, and PD in 15, with a response rate of 35.9. The safety of the drug was assessed in 177, excluding ineligible patients and 3 who dropped out because of the concurrent use of other drugs. Adverse reactions were found in 93.2% of the patients, and abnormal values in clinical laboratory tests in 60.5%. Major unwanted symptoms included fever, nausea, vomiting, and anorexia. Major abnormal changes in laboratory tests were elevated total bilirubin and LDH and abnormal hepatic function. About half the patients had malaise and pain related to the intra-arterial infusion therapy. The one year survival rate was 56.9%, and the duration of survival of 50% of the patients was 407 days.

Adult↗

PubMed1991

Efficacy of internal mammary node dissection in the treatment of breast cancer.

The present study compares clinical and pathological findings and survival data from 410 patients who have undergone extended radical mastectomies in our hospital during the 20 years from 1967 with those derived from 261 who underwent mastectomies without dissections of the internal mammary nodes, in order to determine the value of additional internal mammary node dissection following standard radical mastectomy. Extended radical mastectomy was used in 289 of 361 (80.1%) patients with medial tumors, and in 121 of 310 (39.0%) with lateral tumors. Metastases to the internal mammary nodes were found in 18.5% (76) of all patients, in 20.4% (59) of the patients with medial tumors and in 14.0% (17) of those with lateral tumors. Of the patients with medial tumors, internal mammary node metastases were found in seven of 44 (15.9%) at TNM Stage I, and the rate of metastases rose with advances in stage. Internal mammary node metastases alone, without those to the axillary nodes, were found in 14 patients (4.8%) with medial tumors and in two with lateral tumors. The 10-year survival rate in patients with medial tumors and metastases to the internal mammary nodes only was 67.0%, which was as good as that in patients with metastases to the axillary nodes only. In conclusion, extended radical mastectomy was valuable in the treatment of relatively early medial breast cancer at TNM Stages I and II.

Adult↗

PubMed1991

[Phase I study of CI-898. CI-898 Study Group].

We conducted a phase I study of CI-898 (trimetrexate), a new diaminoquinazoline antifolate in 22 patients with solid cancer in a multicenter collaborative study. The dosage schedule was single-dose intravenous administration (single treatment), followed by one or two courses of 5-day intravenous administration (5-day treatment) at 3-week intervals. Starting at 2 mg/m2 (1 n), the dose was increased up to 15 mg/m2 (7.5 n) for single treatment and 12 mg/m2 (6 n) for 5-day treatment. Evaluable cases numbered 18 for single treatment and 17 for 5-day treatment. In single treatment, the highest dose of 15 mg/m2 caused no serious side effect and did not reach the maximum tolerated dose (MTD). In 5-day treatment, leukocytopenia and thrombocytopenia were found dose dependently, the dose-limiting factor was bone marrow depression, and MTD was 10 mg/m2/day. The leukocyte and platelet counts reached the nadir in 1-3 weeks after initiation of 5-day treatment. The recovery from the nadir required about one week. Subjective side effects included mucitis (mouth, anus), malaise and gastro-intestinal symptoms (nausea, anorexia, diarrhea). None of alopecia, cardiotoxicity and nephrotoxicity were found. In the present phase I study, a tendency of tumor reduction was found in one case each of breast cancer (adenoma) and lung cancer (squamous cell carcinoma). The plasma concentration of the unchanged compound after single treatment showed a biphasic elimination pattern (t1/2 alpha 0.8-1.4 hr, t1/2 beta 9.4-13.0hr). The urinary excretion of the unchanged compound was 14.7-23.5% of the administered dose. In 5-day treatment, no accumulation was found. From the results of the present study, the recommended dosage of CI-898 in the early phase II study was considered to be 8 mg/m2/day intravenously for 5 days (every 3-4 weeks).

Adult↗

PubMed1991

[Predictability of preclinical evaluation of anticancer drugs by human gastrointestinal cancer--nude mouse panel].

We evaluated the predictability to clinical response of experimental effects of various anticancer agents on human cancer--nude mouse panel established in our department. The human cancer lines used were 12 gastric, 4 colorectal, 3 breast, 2 pancreatic cancers and 1 melanoma xenografted into BALB/c athymic nude mice under SPF conditions. Seven mice each with equivalent mean volume of sc inoculated tumor (about 100 mm3) were subjected to the treatment and control groups. Experimental treatment was conducted daily 25 times for antimetabolites, and intermittently 5 times once or twice a week for other drugs. Dosage of each drug adopted was maximal tolerated dose predetermined for the treatment schedule. Four weeks after the initiation of treatment, the therapeutic effect of each experiment was evaluated by the tumor growth inhibition rate (IR) based on the comparison of mean tumor weight between the 2 groups. When the IR was greater than 58%, the drug was evaluated as effective. The clinical response rate of each drug was referred from the result of the phase II study. Direct comparison of effects on 16 experimental chemotherapies in xenografts with responses to the corresponding clinical therapy of each donor patient revealed a fairly high accordance rate (94%). To elucidate the value of human cancer--nude mouse panel as the preclinical secondary screening, the response rates of 8 anticancer drugs treated to 15 cancer xenografts were compared with the cumulative clinical data available in each drug. Generally, the response rates of the human cancer xenografts to the drugs showed fairly good correlations with the cumulative clinical response rates of the corresponding drugs to the same organs. Using this panel, preclinical examinations of 6 new agents under development, including 254 S and other 2 CDDP derivatives, were performed in expectation the positive correlation with further clinical data.

Animals↗