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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 397 records · Page 22Linked to original sources
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↗
PubMed1996

[Phase I study on DMDC].

Phase I study on antimetabolic carcinostatic DMDC was conducted at 16 medical institutions nationwide for patients with various types of malignant tumors. DMDC was administered by intravenous infusion as per the following three schedules: single administration, single repeated administration, and 5-consecutive-day administration. The safety of the compound was examined single administration in 16 patients, by the single repeated administration in 5 patients, and by the 5 consecutive-day administration in 7 patients, for a total of 28 patients. In the single administration trial, 200 mg/m2 (1 n) was given as an initial dose, then increased stepwise to 450 mg/m2 (2.25 n). The single repeated administration trial was conducted at a single dose of 300 mg/m2. One treatment course lasts until recovery from side effects and abnormalities in laboratory test values. As a general rule, the administration was repeated for 2 treatment courses or more. In the 5-consecutive-day administration trial, an initial dose was 30 mg/m2/day (1 n), and increased to 40 mg/m2/day (1.3 n). The dose-limiting factors for both the single and 5-consecutive-day administration trials were decreases in the numbers of leukocytes and neutrophils. The maximum tolerated dose for single administration trial was over 400 mg/m2 (2 n), and for the 5-consecutive-day administration trial 40 mg/m2 (1.3 n). The decrease in the number of leukocytes and neutrophils for both the single administration and 5-consecutive-day administration trial reached its nadir one to two weeks after administration, and recovered in about one week. In the single repeated administration trial, the administration interval for patients who had completed 2 courses was 2 approximately 3 weeks. The plasma half-life of DMDC in the final phase of elimination in the single administration trial was 5.2 approximately 6.3 hours, and no differences were seen among dose levels. The urinary excretion rate was between 32.0 approximately 61.5% until 48 hours after administration. No accumulation was seen in the 5-consecutive-day administration trial. There were no findings to suggest an antitumor effect in the present study. Given the recovery pattern for suppression of marrow, the above mentioned results led us to decide that an recommended method of administration and dosage in an early phase II trial would be 300 mg/m2 per administration by an intravenous infusion every 2 approximately 3 weeks.

Aged↗
PubMed1996

[An early phase II study of gemcitabine hydrochloride (LY 188011). Gemcitabine Cooperative Study Group for Early Phase II].

An early phase II cooperative study of Gemcitabine Hydrochloride (abbreviated to "gemcitabine" herewith) was conducted in patients with a variety of solid tumors (i.e., lung cancer, gastric cancer, pancreatic cancer, colon/rectum cancer, cervical cancer, ovarian cancer and breast cancer) at 56 institutions. The aim of the first step (Step I) was to investigate the feasibility of gemcitabine in a variety of different solid tumors, including lung cancer regarding efficacy and safety. The aim of the second step (Step II) was as a result of step I (Responses were observed) to continue to investigate the efficacy and safety of gemcitabine in chemonaive patients with non-small cell lung cancer. As a Step I study, gemcitabine was administered once weekly at a dose of 800 mg/m2 for a consecutive 3-week period followed by a week of rest, in multiple courses. Among the 29 eligible patients with lung cancer, partial response (PR) was achieved in 3 patients (25.0%, 95% confidence interval: 5.5-57.2%) out of 12 chemonaive patients. Adverse reactions (grade 3 or higher) seen in 29 patients with lung cancer were neutropenia (27.6%), leukopenia (13.8%), decreased hemoglobin (13.8%), thrombocytopenia (10.3%), malaise (6.9%), anorexia (3.4%), nausea/vomiting (3.4%), diarrhea (3.4%), dyspnea (3.4%) and interstitial pneumonia (3.4%). In other types of solid tumors, PR was achieved in 2 (8.7%) out of 23 eligible patients with cervical cancer and in 1 (5.3%) of 19 eligible patients with ovarian cancer, while the use of analgesics became unnecessary in 1 patient with pancreatic cancer. Incidence as well as severity of main adverse reactions in these patients were comparable to those seen in patients with lung cancer. A Step II study, in which gemcitabine was administered once weekly at a dose of 1,000 mg/m2 to chemonaive patients with non-small cell lung cancer, was conducted, referring to the results of Step I and clinical studies conducted overseas. The results of the Step II study demonstrated PR in 5 (14.3%, 95% confidence interval: 4.8 - 30.3%) out of 35 eligible patients with non-small cell lung cancer and that the main adverse reactions were comparable to those seen in the Step I study, posing no tolerability problems in particular.

Adult↗
PubMed1996

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

A late phase II study of LY188011 (gemcitabine hydrochloride), a new synthetic anticancer agent, was conducted at 20 Japanese institutions to evaluate the efficacy and safety of the agent administered alone in patients previously untreated with chemotherapy for primary non-small-cell lung cancer (NSCLC). All of the total 73 patients enrolled were eligible and 69 completed at least one course of LY188011 therapy. All patients were evaluated for safety. The response rate was 26.0% (19/73) of eligible patients. The most common adverse reactions included decreased hemoglobin, leukopenia, neutropenia, anorexia, nausea/vomiting, and malaise. Most adverse reactions were of grade 1 or 2 and only a few grade 3 or 4 reactions were reported. However, since a death occurred due to interstitial pneumonia, careful observation for this event is needed. Based on these results, it may be concluded that LY188011, a new anticancer agent, has adequate efficacy for the treatment of NSCLC and causes few clinically relevant adverse reactions.

Adenocarcinoma↗
PubMed1995

Induction of DNA polymerase beta and gamma in the lungs of age-related oxygen tolerant rats.

To clarify a mechanism for oxygen tolerance in young rats, 3 and 8 week-old rats were exposed to 100% oxygen. All 8 week-old (8W) rats died between 48 and 72h, whereas most 3 week-old (3W) rats survived for more than 72 h under hyperoxia. It was assumed that this difference is attributable to oxygen tolerance in 3W rats compared with 8W rats. To clarify this difference, we measured the change in the activity of DNA polymerase, which is related to the final step of DNA repair. DNA polymerase activity in crude lung extracts from 3W rats increased up to 72 h after oxygen exposure. On the other hand, the activity in 8W rats was decreased at 24 h and 48 h. The activity of DNA polymerase beta, which is related to nuclear DNA (nDNA) repair, was approximately seven times higher in 3W rats than in 8W rats. DNA polymerase beta activities in 3W rats decreased up to 48 h with oxygen exposure, but recovered to pre-exposure levels by 72 h. Moreover, an induction of DNA polymerase gamma, which is related to mitochondrial DNA (mtDNA) replication and/or repair, was observed only in 3W rat lungs after 24 h of oxygen exposure. From these results, we conclude that the induction of DNA polymerase beta and DNA polymerase gamma in lung tissue plays a key role in oxygen tolerance in very young rats.

Age Factors↗
PubMed1995

Stimulation of DNA polymerase gamma activity by proliferating cell nuclear antigen.

DNA polymerase was partially purified from mitochondrial extracts of rat liver by phosphocellulose, DEAE-cellulose, heparin-Sepharose CL-6B and DNA-agarose column chromatography. By these purification steps, DNA polymerase and proliferating cell nuclear antigen (PCNA) were completely separated at the step of heparin-Sepharose CL-6B column chromatography. The isolated DNA polymerase was inhibited by ddTTP, but not by aphidicolin. The enzyme sedimented at about 8 S on 5-20% analytical sucrose density gradient centrifugation. These data showed that the DNA polymerase isolated from mitochondria is gamma in type. After the separation of DNA polymerase gamma and PCNA, the two fractions were remixed and DNA polymerase gamma activity was measured. DNA polymerase gamma activity was stimulated about three-fold or more in the presence of the PCNA fraction. This stimulation was inhibited by the addition of anti-PCNA rabbit IgG2a. In addition, highly purified human recombinant PCNA stimulated the DNA polymerase gamma activity. These results indicate that DNA polymerase gamma, like DNA polymerase delta, is activated by PCNA.

Animals↗
PubMed1995

Blood vascular bed and pericapillary space in rat parathyroid glands.

The blood vascular bed and pericapillary space of the rat parathyroid gland were studied by scanning electron microscopy of vascular casts, freeze-cracked tissue blocks, and NaOH-treated tissue specimens. The findings were supplemented by transmission light and electron microscopy of sectioned tissue samples. The rat parathyroid gland contained a rich network of freely anastomosing capillaries. These capillaries were surrounded by marked pericapillary spaces that were demarcated by basal lamina of both capillaries and parenchymal cells. The pericapillary spaces contained many collagen fibrils and frequently issued some projections running deep into the sheets of parathyroid cells. The latter projections may be useful to supply the parenchymal cells located far from the capillaries. The collagen fibrils may regulate the flow of tissue fluid in the pericapillary space and convey parathyroid hormone, which is released at the apicolateral domain, into the capillaries.

Animals↗
PubMed1995

Proton NMR study of the trimannosyl unit in a pentaantennary N-linked decasaccharide structure. Complete assignment of the proton resonances and conformational characterization.

The chemical shifts of all the ring protons of the three Man residues in a pentaantennary glycan chain have been unambiguously assigned by two-dimensional proton nuclear magnetic resonance (1H-NMR) spectroscopic methods. The study, using chemical shift and J values on the conformation of the trimannosyl unit, revealed that the rotamer about the C5-C6 bond of the alpha 1-->6 linkage in the sequence of Man alpha 1-->6Man beta 1--> is predominantly confined to a gauche-gauche rotamer (omega = 180 degrees, omega = O6-C6-C5-H5) and not to a gauche-trans rotamer (omega = -60 degrees). We do not know of any previous demonstration that the dihedral angle omega (O6-C6-C5-H5) in Man alpha 1-->6Man beta 1--> is preferentially 180 degrees in complex-type N-linked glycans having no bisecting GlcNAc residue.

Amino Acid Sequence↗
PubMed1995

Inactivation of the DCC tumor suppressor gene in a B-cell lymphoma cell line with the alteration of chromosome 18.

A B-cell lymphoma cell line, designated KML-1, was established from pleural effusion of a patient with non-Hodgkin's lymphoma of large-cell type. The lymphoma arose in the pelvis and ran an aggressive clinical course. Chromosome analysis of the cell line exhibited a complex karyotype including the loss of chromosome 18. To evaluate the molecular events in the cell line that may be associated with the development of the lymphoma, we investigated the expression and/or alterations of several classes of human genes, including oncogenes, tumor suppressor genes, and cytokine genes. The expression of the DCC (deleted in colorectal cancer) gene, located on the chromosome 18q21, was extremely reduced in KML-1 cell line, as compared with that in a normal spleen tissue and other 4 lymphoma cell lines by the reverse transcription-polymerase-chain-reaction (RT-PCR) method. This finding suggests that inactivation of the DCC gene might play a role in the pathogenesis of the case of lymphoma.

Adult↗
PubMed1995

The significance of cytological examination on reperfusion in rat small intestinal transplantation.

We examined the cytology of the exudate in preserved intestinal grafts on reperfusion and compared it with the histological findings in rat small intestinal transplantation. The jejunal graft was harvested from the Lewis rat and was preserved in University of Wisconsin solution for 6, 12, 24 and 48 h at 4 degrees C (n = 6, in each group) and was then syngeneically transplanted. On reperfusion, the exudate was collected and studied cytologically. Full thickness biopsies were performed at the end of the preservation and at 30 min after reperfusion for histological examination. Histological examination after reperfusion showed that the crypt layer was preserved until 24 h. However, it was destroyed by 48 h preservation. The cytological findings correlated with the depth of tissue injury shown histologically. The degeneration of villus epithelial cells, the decrease in the content of mucin in both the goblet cells as well as villus cells, and the appearance of crypt cells are all considered to be signs of poor graft viability. Cytological examination is therefore recommended as an effective, non-invasive and real-time method for evaluating graft viability just after reperfusion in small intestinal transplantation.

Adenosine↗
PubMed1995

Extralobar pulmonary sequestration mimicking cystic adenomatoid malformation in prenatal sonographic appearance and histological findings.

An infant girl with extralobar pulmonary sequestration (PS) composed of congenital cystic adenomatoid malformation (CCAM)-like structure is presented. Initially, the antenatal sonographic findings indicated CCAM. The macroscopic findings of the resected specimen were compatible with extralobar PS; however, the microscopic findings showed cystic structure mimicking type II CCAM. The combination of PS and CCAM is rare, and it is likely that the embryological origin is common to both. There is confusion in the classification of these two congenital anomalies. In this report, the histological and sonographic findings of PS and CCAM are discussed.

Adult↗
PubMed1995

The protective effect of hyperbaric oxygenation on the small intestine in ischemia-reperfusion injury.

Hyperbaric oxygenation has been used as the method of treatment in several ischemic diseases, but its effectiveness still remains controversial. The authors investigated the effect of hyperbaric oxygenation on ischemia-reperfusion injury of the small intestine using a rat model. Wistar King A Makino (WKAM) rats were subjected to 120 minutes of superior mesenteric artery occlusion before reperfusion, with 90 minutes of hyperbaric oxygenation (two absolute atmospheric pressure in an experimental hyperbaric chamber) during ischemia in group A and immediately after reperfusion in group B, and no hyperbaric oxygen was provided to group C. Jejunal samples 1.5 cm in length were taken at the end of ischemia in all groups, at 30 minutes after reperfusion in groups A and C, and at 120 minutes after reperfusion in groups B and C, for the measurement of adenine nucleotides (high-performance liquid chromatography method) and for histological examination (hematoxylineosin [HE] staining). The survival rate was significantly higher in group A than in group C. The amount of adenosine triphosphate in the samples was not significantly different among the three groups, whereas the energy charge at the end of ischemia was significantly higher in group A than in group C. Histologically, the damage to the mucosa and the longitudinal muscle layer decreased in group A compared with that observed in groups B and C. These results suggest that hyperbaric oxygenation during ischemia is able to ameliorate ischemia-reperfusion injury in the rat small intestine.

Animals↗