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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 181 records · Page 10Linked to original sources

Amino acids and peptides. XXIII. Leu-enkephalin analogs containing a fluorinated amino acid at position 2, 4 or 5.

Fluorinated analogs of Leu-enkephalin were synthesized by the solution method and the solid-phase method. The synthetic peptides were examined for opioid activities on mouse vas deferens and guinea pig ileum. Among the synthetic peptides,[D-Ala2,Leu(F3)(2R,4S)5]enkephalin and [D-Ala2,Leu(F3)(2S,4R)5]enkephalin exhibited potent opioid activity, and [Leu(F3)(2S,4R)5]enkephalin exhibited high delta-receptor selectivity.

Amino Acid Sequence

Simultaneous dual myocardial imaging with iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) and thallium-201 in patients with coronary heart disease.

To assess the clinical value of simultaneous dual myocardial imaging with iodine-123-beta-methyl-iodophenyl-pentadecanoic acid (123I-BMIPP) and thallium-201 (201Tl), myocardial imaging was performed at rest and during exercise in seven patients with coronary heart disease. When 123I-BMIPP and 201Tl images were compared, the initial exercise and resting images agreed 87% and 64%, respectively. In the initial resting images, the regional uptake of 123I-BMIPP was frequently less than that of 201Tl. The incidence of exercise-induced reversible defects by 201Tl in the Tl > BMIPP regions was significantly higher than that in the Tl = BMIPP regions (57% vs 4%, p < 0.01) and the incidence of coronary narrowing of more than 90% in the Tl > BMIPP regions was also significantly higher than that in the Tl = BMIPP regions (91% vs 38%, p < 0.01). In addition, this disparity (Tl > BMIPP) was found more frequently in regions with abnormal wall motion than in regions with normal wall motion (hypokinetic regions; 68%, severe hypokinetic or akinetic regions; 50%, vs normokinetic region; 4%, p < 0.01). In contrast, the uptake of 123I-BMIPP correlated closely with that of 201T1 in normal myocardium and the uptake of both 123I-BMIPP and 201Tl was severely reduced in myocardium with severe ischemia during exercise and prior infarction. These results indicate that dual myocardial imaging with 123I-BMIPP and 201Tl may provide a unique means of identifying patients with metabolically disturbed myocardium, such as hibernating and stunned myocardium.

Aged

Neurons with intensely negatively charged extracellular matrix in the human visual cortex.

Neurons in the human visual cortex were demonstrated to possess an intensely negatively charged surface coat which was stained with cationic iron colloid and aldehyde fuchsin. Digestion with hyaluronidase eliminated both the iron colloid and fuchsin stainings of the coats. Treatment with chondroitinase ABC, heparitinase and keratanase eliminated the iron colloid staining of the coats, but did not interfere with the fuchsin staining. Electron microscopy of ultrathin sections revealed that the cationic iron particles were preferentially deposited in the perineuronal tissue spaces. These findings indicate that the surface coats consist of sulfated proteoglycans, which, as an extracellular matrix, occupy the perineuronal tissue spaces. This study further demonstrates that neurons with such surface coats are identical with neurons labeled with lectin Vicia villosa agglutinin. The cell surface glycoproteins reactive to this lectin may not be the structural elements of the sulfated coats since the lectin labeling was not interrupted by the hyaluronidase digestion.

Anions

Microcirculatory patterns in human pancreas: supplementary observations of vascular casts by scanning electron microscopy.

The blood vascular bed of two human pancreata was replicated partially by arterial perfusion of intentionally reduced amounts of low viscosity methacrylate resin, to be observed with a scanning electron microscope. The findings were compared with those obtained from a pancreas replicated completely by a sufficient amount of resin. Complete replication confirmed our previous findings (MURAKAMI et al., 1992) that many exocrine lobules contained one or more endocrine islets, which preferentially issued insulo-acinar portal vessels continuous with the lobular capillaries. Incomplete replication demonstrated that the casting medium filled blood capillaries in the endocrine islets more promptly than those in the exocrine lobules and secretory ducts. Furthermore, islet-containing lobules allowed a more rapid resin flow to the exocrine tissue via the insulo-acinar portal route than did the lobules lacking an islet. Since the resin medium used had the viscosity of blood and was injected under physiological pressure, the results obtained by the incomplete arterial injections are believed to suggest the physiological state of blood flow in the pancreas.

Adult

The occurrence of neurons with strongly negatively charged surface coats in mammalian, avian, reptilian, amphibian and piscine brains.

Neurons with strongly negatively charged surface coats were recognized in mammalian, avian, reptilian, amphibian and piscine brains. Many large-sized neurons had strongly negatively charged surface coats in the visual cortex and brain stem of the cow, cat, guinea pig, mouse, quail and parakeet. Such neurons were also seen in the brain stem of the lower vertebrates such as the house lizard, Japanese terrapin, bullfrog, newt, carp and sweetfish.

Amphibians

Chemo-occlusion for the treatment of liver cancer. A new technique using degradable starch microspheres.

The use of particulate embolic agents combined with regional chemotherapy in the treatment of hepatocellular carcinoma and metastatic liver cancer has been widely investigated over the past decade. The rationale for the use of such agents is to provide vascular blockade, resulting in a reduced or halted blood flow. This increases the in situ time, tumour exposure and, thus, efficacy of any coadministered cytotoxic drug. Of all the embolic agents and techniques available, degradable starch microspheres (DSMs) are the agents that have been evaluated most extensively. DSMs are non-toxic, are readily degradable and provide temporary vascular occlusion. Phase II and III clinical trials have demonstrated the efficacy of DSM when coadministered with chemotherapeutic drugs (chemo-occlusion), as measured by tumour response. Indeed, compared with drug therapy alone, a significantly greater tumour response is associated with chemo-occlusion, for patients with either hepatocellular carcinoma or metastatic liver cancer. The use of combination or multi-modular therapies have, in recent years, been investigated. The therapeutic benefits associated with chemo-occlusion would suggest that this technique might have a potential application as an adjuvant, or neoadjuvant therapy, for example, in reducing tumour recurrence after surgical resection in hepatocellular carcinoma, or downstaging a tumour prior to surgical resection, respectively. Furthermore, comprehensive management of patients with liver metastases and potential extrahepatic involvement may well be achieved by a combination of DSM chemo-occlusion and systemic chemotherapy. Large, randomised trials are, however, required to access more fully the clinical benefits associated with chemo-occlusion, such as, quality of life, time to tumour progression and survival. Regionally occlusive techniques administered with cytotoxic agents have also shown potential in the treatment of alternative cancers, for example, breast and pancreatic carcinomas. However, these therapies require further evaluation.

Antineoplastic Agents

Changes in the activities of DNA polymerases in growing rat lungs.

We hypothesized that cellular proliferation and the capacity to repair DNA damage in the lung might differ during the pre- and postnatal periods, because the lung is exposed to higher oxygen concentrations and/or various mutagens after birth. In order to test this hypothesis, changes in DNA content and the activities of DNA polymerase alpha and beta were studied in the lungs of 1-day prenatal to 42-day postnatal rats. Total DNA polymerase activity reached its highest level at 1 day prenatal and 1 day after birth. The activity decreased exponentially by 28% up to 14 days of age, a change inversely related to the change in DNA content. The change in total DNA polymerase activity agreed closely with the change in DNA polymerase alpha activity, but not the activity of the beta form, although small elevations in both DNA polymerase alpha and beta were observed on day 3, possibly reflecting the mechanical effect of delivery. The activity of DNA polymerase beta remained relatively constant from 1 day before birth to 21 days after birth, varying by only about 5%. From these results, it is concluded that: (1) cellular proliferation in the lung is most active during the first 2 weeks after birth as supported by the increases in DNA polymerase alpha activity and DNA content, and (2) anticipating the oxygen enriched atmosphere after birth, the level of DNA polymerase beta, involved in the DNA repair system, is already elevated during the prenatal period and remains constant throughout the postnatal period.

Animals

Pharmacologic profiles of YM934, a novel potassium channel opener.

Pharmacologic profiles of YM934, a newly synthesized 1,4-benzoxazin derivative K channel opener were evaluated in in vitro and in vivo experiments. In isolated rat portal vein, YM934 and a benzopyran derivative K channel opener lemakalim inhibited the frequency of spontaneous rhythmic contractions concentration dependently, with IC50 values of 14 and 38 nM, respectively. These inhibitory effects were competitively antagonized by glibenclamide (an ATP-sensitive K channel blocker; 10(-7)-3 x 10(-6) M). In isolated rabbit aorta, YM934 (10(-8)-10(-6) M) and lemakalim (10(-8)-10(-6) M) relaxed the contractions induced by 20 mM KCl concentration dependently but were ineffective against the contractions induced by 50 mM KCl. YM934 (10(-8)-3 x 10(-6) M) and lemakalim (3 x 10(-8)-10(-5) M), but not the calcium antagonist nifedipine, relaxed the contractions induced by norepinephrine (NE 10(-6) M) or prostaglandin F2 alpha (PGF2 alpha 3 x 10(-6) M) in the aorta. In pentobarbital-anesthetized dogs, YM934 (1-10 micrograms/kg intravenously, i.v.) dose-dependently increased coronary artery blood flow (CBF), and decreased total peripheral resistance (TPR) and mean blood pressure (MBP). YM934 selectively increased CBF, but had little effect on vertebral, carotid, mesenteric, renal and femoral artery BF. These vasodilatory effects of YM934 were antagonized by glibenclamide. YM934 is a potent K channel opener and possesses potent vasodilatory effects, with particularly pronounced effects on the coronary artery. These effects of YM934 may, like lemakalim, be mediated by opening of ATP-sensitive K channels.

Anesthesia

[Recent advance in chemotherapy for breast cancer].

In cases of recurrent progressive breast cancer, ADM, CPM, 5-FU, MTX, MMC and vinca alkaloids have proven to be effective, but CMF and CAF have been considered the standard chemotherapy regimen. But no regimen can cure recurrent progressive breast cancer. Thus, the aim in recent years has been greater efficacy and longer survival by means of dose-intensity. The latter has become possible through G-CSF, the patient's own bone marrow transplant or implantation of peripheral vascular cells and the like, resulting in 70-90% efficacy. The CR rate also has reached over 50%, and long-term survival has been achieved. Clinical research has been thus moving ahead, encouraged by the promise of chemotherapy employing such huge doses. However, in combination with other forms of therapy, a great number of controversial problems are encountered which require study. Recently, a number of agents such as Taxotere or CPT-11 have been used effectively in combination for breast cancer, and they appear to be very promising.

Antineoplastic Agents, Phytogenic

[Phase I clinical trial of RP 56976 (docetaxel) a new anticancer drug].

A multicenter phase I clinical trial of RP 56976 (docetaxel), a new anticancer drug, was performed with single and repeated doses. Based on the results of phase I clinical trials conducted in the United States and Europe, the starting dose was 10 mg/m2. The dose was subsequently increased to 20, 50, 70 and 90 mg/m2. A dose of 60 mg/m2 was additionally tested. Single administrations of the six dose levels were performed in a total of 27 patients via intravenous drip infusion over one hour. Ten of the patients subsequently received repeated doses at three of the dose levels in the same manner. The dose limiting factor (DLF) of docetaxel is leukopenia (especially, neutropenia). Based on the observation of the DLF, the maximum tolerated dose (MTD) was determined to be 70-90 mg/m2. The white blood cell count reached a nadir about 9.5-19.5 days (median) after administration, and took 7-11 days (median) to recover. Other adverse reactions observed were nausea/vomiting anorexia, alopecia, diarrhea, fatigue and fever, which were all acceptable. The results of this trial suggest that a dosage regimen of 60 mg/m2 at 3- to 4 week intervals is appropriate in an early phase II clinical trial.

Adolescent

[An early phase II clinical study of RP56976 (docetaxel) in patients with cancer of the gastrointestinal tract].

An early phase II clinical study of RP56976 (docetaxel), a new semisynthetic agent, was conducted in patients with apparatus digestorius cancer. Two or more intravenous doses of 60 mg/m2 were administered with dose-free intervals of 3-4 weeks. Of the 44 patients enrolled, 32 patients (15 patients with gastric cancer, 16 patients with colon cancer, and 1 patient with pancreatic cancer) completed the scheduled course of treatment. For antitumor efficacy in the 15 patients with gastric cancer that completed the study, 3 showed a partial response (PR)(20.0%). Of the 16 patients with colon cancer that completed the study, 1 showed a partial response (PR)(6.3%). No efficacy was noted in the patient with pancreatic cancer. All three patients with gastric cancer showing a partial response (PR) to docetaxel had displayed no response to previous chemotherapy. Evaluation was made for the primary gastric lesion and metastatic lesions in cervical lymph nodes and liver. The most frequent adverse reactions included leukopenia (100%) and neutropenia (97.2%) and subjective/objective adverse reactions included alopecia (80.6%), anorexia (72.2%), fatigue (52.8%), fever (47.2%) nausea/vomiting (47.2%), and diarrhea (38.9%). Leukopenia was of Grade III or more in 75.0% of the patients and neutropenia was of Grade III or more in 91.7%. All other adverse reactions were acceptable. The results suggest that docetaxel is an effective anticancer agent for gastric cancer.

Adenocarcinoma

[An early phase II clinical study of RP56976 (docetaxel) in patients with breast cancer].

An early phase II clinical study of RP56976 (docetaxel), a new anticancer agent of plant origin, was conducted in patients with breast cancer at 20 Japanese collaborative institutions. Docetaxel was administered at two or more doses of 60 mg/m2 by intravenous infusion with dose-free intervals of 3-4 weeks, and the efficacy and safety was evaluated. Of the 51 patients enrolled, 50 patients completed the scheduled course of treatment. Two patients showed a complete response (CR) and 19 showed a partial response (PR) with a response rate of 42.0%. The response rates based on the efficacy for metastatic lesions in soft tissue, liver and lung, were 46.2% (18/39), 37.5% (3/8), and 38.5% (5/13), respectively. Of the 50 patients who completed the study, 48 patients had previously been treated for the present malignancy. Forty-seven patients had previously been treated with chemotherapy and showed a response rate of 40.4% (19/47). The response rate in those who had received chemotherapy composed of anthracyclines and other agents was 44.1% (15/34). Grade 3 or more severe leukopenia and neutropenia developed in 43 patients (84.3%) and 48 patients (94.1%), respectively. Other adverse reactions which occurred in a Grade 3 or more severe form included nausea/vomiting (1 patient), anorexia (5 patients), diarrhea (4 patients), fatigue (2 patients), and alopecia (20 patients). Except for alopecia, most adverse reactions were generally transient and reversible without any specific treatment.

Adult

[Phase II clinical study of RP56976 (docetaxel) in patients with carcinoma ovarii or carcinoma colli uteri].

An early phase II clinical study of RP56976 (docetaxel), a new semisynthetic agent, in patients with carcinoma ovarii or carcinoma colli uteri was undertaken by a cooperative study group of 23 institutes. Docetaxel was administered at an initial intravenous dose of 60 mg/m2 with dose-free intervals of 3-4 weeks, and its efficacy and safety were evaluated. Of the 47 patients with carcinoma ovarii enrolled, 44 patients were eligible and 36 patients completed the scheduled course of treatment. Of the 23 patients with carcinoma colli uteri enrolled, 20 patients were eligible and 15 patients completed the scheduled course of treatment. For antitumor efficacy in patients with carcinoma ovarii, 1 patient showed partial response (PR), 10 showed no changes (NC) (2 showed minor response (MR)), and 25 had progressive disease (PD). The overall response rate was 2.8% (1/36). Of patients with carcinoma colli uteri, 7 patients showed no changes (NC) (1 patient showed minor response (MR)), 8 patients had progressive disease (PD). Major adverse reactions included 64/65 (98.5%) leukopenia, 56/59 (94.9%) neutropenia, 40/60 (61.5%) decrease of hemoglobin, 12/64 (18.8%) thrombocytopenia, 30/65 (46.2%) anorexia, 23/65 (35.4%) nausea/vomiting, 37/65 (56.9%) alopecia, and 26/65 (40.0%) fatigue, all of which were mild.

Adenocarcinoma, Clear Cell

[Early phase II clinical study of RP56976 (docetaxel) in patients with primary pulmonary cancer. Docetaxel Cooperative Study Group for Lung Cancer].

An early phase II clinical study of RP56976 (Docetaxel), a new anticancer agent of plant origin, was conducted in patients with primary pulmonary cancer as a multicentered study involving 28 Japanese institutions. Docetaxel was administered at an intravenous dose of 60 mg/m2 based on the results of a phase I clinical study, and efficacy and safety were examined. Of the 65 patients enrolled, 57 patients were evaluated to have completed the scheduled course of treatment by the Evaluation Committee. The antitumor effect in patients with non-small cell lung cancer was 21.4% (9/42). In patients not previously treated, the antitumor effect was 30.0% (6/20), in patients previously treated the antitumor effect was 13.6% (3/22), and in 13.3% (2/15) of patients with small cell lung cancer. This shows that docetaxel had an efficacy for non-small cell lung cancer. Hematological adverse reactions included leukopenia and neutropenia of Grade III or more as specified in the Adverse Event Reporting Form proposed by the Japan Society for Cancer Therapy in 53.3% (32/60) and 78.3% (47/60) patients, respectively. Other major adverse reactions included alopecia and anorexia. Neurological symptoms developed at a low frequency and were mild in severity.

Adult

[Late phase II clinical study of RP56976 (docetaxel) in patients with non-small cell lung cancer].

A late phase II clinical study of RP56976 (Docetaxel) was conducted in patients with non-small cell lung cancer. Patients with non-small cell lung cancer in Stage IIIB and Stage IV not previously treated were enrolled. Docetaxel was administered at a dose of 60 mg/m2 based on the results of a phase I and an early phase II clinical study, and the efficacy and safety were examined. Of the 77 patients enrolled, 72 patients were evaluated to have completed the scheduled course of treatment by the Evaluation Committee. A partial response (PR) was seen in 18 patients, and the overall response rate was 25.0%. The response rate classified by clinical stage was 28.0% (7/25) in patients with Stage IIIB and 23.4% (11/47) in patients with Stage IV. Hematological adverse reactions included leukopenia of Grade III or more in 53.3% (40/75) and neutropenia of Grade III or more in 86.7% (65/75) as specified in the Adverse Event Reporting Form proposed by the Japan Society for Cancer Therapy. Other major adverse reactions included alopecia, asthenia, and fever, all of which were tolerable. From these results, the efficacy of docetaxel for the treatment of non-small cell lung cancer was confirmed.

Adolescent

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent breast cancer].

A late phase II clinical study of RP56976 (Docetaxel), a new semisynthetic anticancer agent, was conducted in patients with advanced/recurrent breast cancer. RP56976 (Docetaxel) was in general administered at an intravenous dose of 60 mg/m2 with dose-free intervals of 3-4 weeks. Of the 74 patients enrolled, 64 patients completed the scheduled course of treatment. Three patients showed complete response (CR), 32 patients partial response (PR), 3 patients minor response (MR), 18 patients no change (NC), and 8 patients had progressive disease (PD). The overall response rate was 54.7%. The response rate in patients who previously had received chemotherapy was 55.7%, and the response rate in patients who had resistance to anthracycline agents or who did not respond to previous treatment was 58.7%. Adverse reactions included nausea/vomiting in 38 patients (57.6%), fatigue in 46 patients (69.7%), anorexia in 46 patients (69.7%), fever in 26 patients (39.4%), and alopecia in 60 patients (90.9%), all of which were tolerable. Abnormal laboratory findings included leukopenia (Grade III or more) in 57 patients (86.4%) and neutropenia (Grade III or more) in 56 patients (86.2%). The results show that RP56976 (Docetaxel) is an excellent agent with high antitumor effect for the treatment of advanced/recurrent breast cancer.

Adult