Search PubMed⌕ Search

Biomedical subjects

T Furuta

Publications and source records attributed to T Furuta.

At least 271 records · Page 15Linked to original sources

[Study on the extent of peritumoral edema in glioma: its correlation with the proliferative potential and tumor-infiltrating mononuclear cells].

The correlation between the extent of peritumoral edema and the proliferative potential or the infiltration of mononuclear cells was studied in 17 gliomas. The peritumoral edema was evaluated on contrast enhanced CT scan as the ratio of the low density area around the tumor to the enhanced high density area. The proliferative potential and the infiltration of mononuclear cells into the tumor were investigated immunohistochemically using monoclonal antibody (MAb) against DNA polymerase alpha and anti-Leu MAb's respectively. There was a significant correlation between the extent of the peritumoral edema and the percentage of DNA polymerase alpha positive cells. The degree of the infiltration of mononuclear cells into the tumor tissue also correlated with the extent of peritumoral edema. In gliomas with high proliferative potential and/or severe infiltration of mononuclear cells, the peritumoral edema may be aggravated by disruption of the blood-brain-barrier and increased vascular permeability.

Brain Edema↗

The effect of a new immunosuppressive agent, FK-506, on xenogeneic neural transplantation in rodents.

This study examines the effect of a novel immunosuppressive agent FK-506 (FK) on the survivability of embryonic (E14) rat ventral mesencephalic tissue after intracerebral grafting to the lateral ventricle of adult mice. The recipient mice were given FK in doses of 10 mg/kg or 1 mg/kg for 2 weeks postgrafting, at which time they were sacrificed and histologically processed except for one group of animals on the high dose (10 mg/kg). In this group most animals died from side effects of the drug during the following days. Only the mice receiving the high dose of FK displayed healthy grafts without signs of rejection.

Animals↗

Reversible reaction via a carbanion intermediate in the elimination of ammonia from L-histidine catalysed by histidine ammonia-lyase.

L-[5'-2H2]Histidine was used as a substrate to investigate the enzymatic reaction mechanism with histidine ammonia-lyase from Pseudomonas fluorescens. The study was performed to determine the exchange rate of deuterium at C-5' of the imidazole ring with solvent hydrogen relative to the net urocanic acid production. The extent of hydrogen exchange at C-5' of histidine or urocanic acid was measured by gas chromatography-mass spectrometry-selected ion monitoring, monitoring the molecular ion intensities of the respective gas chromatographic derivatives, at m/z 380 and 379 for histidine and at m/z 267 and 266 for urocanic acid. The observed hydrogen exchange at C-5' suggested a reversible mechanism via a carbanion intermediate in the reaction with histidine ammonia-lyase.

Ammonia↗

Antitumor activity of a camptothecin derivative, CPT-11, against human tumor xenografts in nude mice.

The antitumor effects of the camptothecin (CPT) derivative CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin , were tested on human tumor xenografts in nude mice. CPT-11 showed antitumor activity higher than that of Adriamycin, 5-fluorouracil, or futraful, with little or no reduction of body weight being observed in the mice. The growth of colon adenocarcinoma Co-4 was significantly inhibited after a single i.v. injection of CPT-11 at 25, 50, or 100 mg/kg. The single i.v. injection was also significantly effective against mammary carcinoma MX-1 and gastric adenocarcinoma St-15. All of the mice bearing MX-1 tumors were cured by the administration of CPT-11 every 4 days for a total of three treatments at a total dose of 200 mg/kg given i.v. or of 400 mg/kg given p.o. Three i.v. or oral treatments were also effective against Co-4, St-15, gastric adenocarcinoma SC-6, and squamous-cell lung carcinoma QG-56. To achieve the same efficacy attained by i.v. injection, however, oral doses 2-4 times higher than the i.v. doses were required. When the total dose was fixed at 100 mg/kg, a triple i.v. injection was most effective, followed by a single i.v. injection and, finally daily p.o. administration for 10 days. Although SN-38 (7-ethyl-10-hydroxycamptothecin), a metabolite of CPT-11, showed much stronger cytotoxic activity in vitro than did CPT-11, its antitumor effects were similar, if not inferior, to those of CPT-11 in vivo at the same dose level. CPT-11 was converted into SN-38 by human tumors, but the sensitivity of these tumors to CPT-11 in vivo was independent of their ability to produce SN-38. These results suggest that CPT-11 may be clinically effective, depending on the schedule of administration, but that its effectiveness is not related to the ability of the tumor to produce SN-38.

Adenocarcinoma↗

Cardiovascular characterization of SD-3211, a novel benzothiazine calcium channel blocker, in isolated rabbit hearts.

The cardiovascular effects of SD-3211, a novel benzothiazine Ca++ channel blocker, were compared with those of diltiazem and nicardipine in Langendorff-perfused rabbit hearts. SD-3211 was more potent in increasing coronary artery flow than in depressing cardiac function (i.e., contractile force, heart rate and conduction time). The relative specificity of SD-3211 for coronary vasodilation to cardiodepression was clearly greater than that of diltiazem, but less than that of nicardipine. Thus, the present study demonstrates that SD-3211, despite a non-dihydropyridine type of Ca++ channel blocker, can be characterized as a potent coronary vasodilator with a little effect on cardiac function.

Animals↗

Anti-ischaemic and vasospasmolytic effects of a novel Ca2+ channel blocker, SD-3211, in vitro.

1. The present study was undertaken to determine the vasospasmolytic activity of a novel non-dihydropyridine type of Ca2+ channel blocker, SD-3211, in isolated canine coronary arteries and its ability to reduce myocardial ischaemic damage in isolated perfused rabbit hearts. 2. The vasospasmolytic effect of SD-3211 was investigated using 3,4-diaminopyridine-induced rhythmic contraction, in comparison with its enantiomer (SD-3212), nicardipine and diltiazem. SD-3211 was shown to reduce the peak tension and increase the contraction frequency. The order of potency for the relaxation of the peak tension was as follows: nicardipine greater than SD-3211 greater than diltiazem greater than SD-3212 and being compatible with that for the relaxant effects of these compounds on KCl-induced contraction in the same specimen. 3. Furthermore, the effect of SD-3211 on myocardial damage due to global ischaemia for 60 min followed by 60 min of reperfusion was examined. SD-3211 at a concentration of 2 X 10(-8) mol/L was given for 40 min before and again for 60 min after the ischaemia. SD-3211 attenuated the increase in leakage of creatine phosphokinase from the hearts and the decrease in pH of perfusate during reperfusion, while concomitantly providing a significant improvement in the post-ischaemic recovery of developed tension. 4. These results suggest that SD-3211 has properties to reduce coronary vasospasm and to provide protection against ischaemic damage, both of which may have beneficial actions in the treatment of ischaemic heart disease.

4-Aminopyridine↗

Synthesis and antitumor activity of 20(S)-camptothecin derivatives: carbamate-linked, water-soluble derivatives of 7-ethyl-10-hydroxycamptothecin.

Novel 36 derivatives (6), bonding the phenolic hydroxyl group of 7-ethyl-10-hydroxycamptothecin (4) with diamines through a monocarbamate linkage, were synthesized and their antitumor activity was evaluated in vivo. The derivatives were soluble in water as their HCl salts with the E lactone ring intact and exhibited significant antitumor activity. One of the derivatives, 6-27 showed excellent activity against L1210 leukemia and other murine tumors. The structure of its hydrochloride trihydrate (CPT-11) was determined by spectroscopic and crystallographic methods.

Animals↗

Chemical modification of an antitumor alkaloid camptothecin: synthesis and antitumor activity of 7-C-substituted camptothecins.

A radical substitution reaction of 20(S)-camptothecin (1) with methanol furnished 7-hydroxymethylcamptothecin (2). Reaction of 1 with primary alcohols higher than methanol gave 7-alkylcamptothecins (4), of which alkyl groups were one carbon less than the alcohols used and also 7-hydroxyalkylcamptothecins (5). For the preparation of 7-alkylcamptothecin (4), aldehydes were used as a radical source and several alkylated derivatives were synthesized. 7-Acyloxymethyl derivatives (6), 7-carbaldehyde (7), iminomethyl derivatives (10), acid (11), esters (12) and amides (13) were synthesized starting from 2. 7-Ethyl- (4b) and 7-propylcamptothecin (4c), acyloxymethyl compounds 6a, 6c and ethyl ester (12b) exhibited higher antitumor activity than 1 against L1210 in mice.

Animals↗

Synthesis and antitumor activity of 20(S)-camptothecin derivatives: A-ring modified and 7,10-disubstituted camptothecins.

20(S)-Camptothecin derivatives having nitro, amino, chloro, bromo, hydroxyl and methoxyl groups in the A-ring were synthesized. B-Ring hydrogenated camptothecin (2a) was converted into 10-hydroxycamptothecin (6e) by treatment with lead tetraacetate in trifluoroacetic acid. 10-Substituted derivatives (6) were obtained by a photoreaction of N-oxides (9). The cytotoxicity of the A-ring modified camptothecins was evaluated against KB cells in vitro and leukemia L1210 in mice. 7-Ethyl-10-hydroxycamptothecin (6i) was identified as a potential derivative for further modification.

Animals↗

[Immunohistochemical study for choroid plexus papillomas and ependymomas].

An immunohistochemical study of glial fibrillary acidic protein (GFAP), S-100 protein, cytokeratin (CKER), epithelial membrane antigen (EMA), and transthyretin (TTR) was carried out on 11 cases of choroid plexus papilloma (CPP) and 19 of ependymoma, using the peroxidase antiperoxidase technique. Among the 11 cases of CPP, all 11 were positive for CKER, EMA, and TTR, 10 for S-100 protein, and five for GFAP. Most of the GFAP-positive papilloma cells were simultaneously positive for CKER. However, these GFAP-positive cells were negative for TTR. Among the 19 cases of ependymoma, 16 were positive for GFAP, 17 for S-100 protein, three for CKER, eight for EMA, but none for TTR. Some GFAP-positive cells were also stained for CKER. However, TTR was not found in any of the ependymal cells. These findings suggested that CPP cells which show ependymal or glial differentiation lost the ability to synthesize TTR which is known to be synthesized in the epithelial cells of the choroid plexus. The more GFAP-positive cells present in a CPP, fewer TTR-positive cells are present. Though CPPs are usually easily distinguishable from ependymomas, occasional doubt arises concerning the differential diagnosis between CPP and papillary ependymoma. TTR can be a very useful diagnostic marker of CPP.

Adult↗

[The effect of a new immunosuppressive agent, FK-506, on xenogeneic neural transplantation in rodents--comparison with cyclosporin A].

The present study was performed to compare the immunosuppressive effect of FK-506 (FK) with cyclosporin A (CyA) in xenogeneic neural transplantation in rodents. The solid grafts of embryonic ventral mesencephalic tissue from 14-day rat embryos were transplanted into the right lateral ventricle of 20 mature male mice using a stereotactic approach, and the mice were sacrificed 14 days after transplantation. The removed brains, which were sectioned coronally, were stained with antibodies against glial fibrillary acidic protein (GFAP), Lyt-2 or tyrosine hydroxylase (TH) in addition to hematoxylin-eosin and Nissl stainings. The subcutaneous (s.c.) administration of FK at a dose of 10.0 mg/kg daily for 14 days enabled the neural xenografts to survive and grow (n = 5), although all of the neural xenografts treated with CyA at a dose of 10.0 mg/kg s.c. (n = 5) or FK at a dose of 1.0 mg/kg s.c. (n = 5) daily for 14 days and ones treated without such an immunosuppressive agent (n = 5) were rejected by immunological reactions. We conclude that FK is a more powerful immunosuppressive agent than CyA in xenogeneic neural transplantation as well as in cardiac and renal allograftings.

Animals↗

Modified technique of Pringle's maneuver in resection of the liver.

Crushing of the hepatic parenchyma with hepatic clamps to minimize blood loss during resection of the liver leads to mechanical damage of hepatocytes. Pringle's maneuver may precipitate liver failure by hepatic warm ischemia as well. Therefore, we controlled bleeding from the surface of the resection by using light compression on the hepatic parenchyma with a band while applying a hepatic arterial clamp at the hepatic hilus. This vascular control method can be done because the portal pressure is about one-tenth of the hepatic artery pressure and provides an efficient and harmless transection of the liver.

Animals↗

[Combination therapy of CPT-11, a camptothecin derivative, with various antitumor drugs against L 1210 leukemia].

Antitumor effect of CPT-11 in combination with cyclophosphamide (CY), nimustin hydrochloride (AC-NU), thio-TEPA (TESPA), methotrexate (MTX), 5-fluorouracil (5-FU), cytosine arabinoside (ara-C), thioinosine (6-MPR), adriamycin (ADM), bleomycin (BLM), mitomycin C (MMC), actinomycin D (ACT-D), vincristine sulfate (VCR), etoposide (VP-16) or cisplatin (CDDP) against L 1210 murine leukemia was investigated. The combination treatment of CPT-11 with CY, ACNU, ADM, CDDP, TESPA and ACT-D showed synergistic effects and significantly prolonged the survival time of L 1210-inoculated mice compared with CPT-11 alone or antitumor drug alone. Although the combination with 5-FU, 6-MPR, VP-16, MMC or VCR had synergistic effect for some schedules exceptionally with ara-C, MTX or BLM had slight synergistic effect against L 1210.

Animals↗

[A long-term survival case of advanced gastric cancer undergoing radical gastrectomy by second-look operation after successful chemotherapy (CDDP, MMC, 5-FU)].

A 55-year-old woman with gastric cancer underwent laparotomy and was found to have an unresectable tumor characterized by S3 (invasion of the pancreas), N3, P0 and H0. She was then treated by combined administration of cisplatinum, mitomycin C and 5-fluorouracil. A remarkable response (CR) was confirmed by upper gastrointestinal roentgenography and endoscopy. Upon reoperation about 8 weeks after chemotherapy, a successful radical total gastrectomy with R2 (partially R3) lymphnode dissection was performed. Histological examination of the specimens, including the stomach and lymphnodes, revealed no cancer cells in any region (pCR). She had been given UFT and PSK for 4 years 4 months after reoperation. She has lived for 5 years 2 months after reoperation without any signs of recurrence or metastases.

Adenocarcinoma↗

[Therapeutic effect of transarterial infusion immunochemotherapy for metastatic liver cancer].

In order to improve therapeutic efficacy for metastatic liver cancer, intermittent transarterial administration of BRM in combination with anticancer drugs was performed by use of reservoir apparatus. A total of 22 patients (12 cases of gastric cancer, 6 of colon cancer, 2 of pancreas cancer, 1 of gall bladder cancer and 1 of biliary tract carcinoid) were treated according to the following schedule: both 10 mg of ADM (or MMC) and 0.5 KE (or 1.0 KE) of OK-432 were administered on day 1 and 40 x 10(4) JRU of recombinant interleukin 2 (r-IL 2) on day 4, 7 and 11. The treatment was repeated as many times as possible. In terms of direct antitumor effect and decrease of tumor marker, the response rate was 43% (6 cases out of 14) and 75% (9 cases out of 12), respectively. As for performance status, improvement, no change and deterioration were seen in 4 cases, 8 cases and 3 cases, respectively. Even though 13 patients died, 8 of them survived more than 300 days. In the case of gastric cancer patients with liver metastasis, 50% survival time of 12 cases was 334 days, while that of 30 cases, who were administered anticancer drugs only systemically, was 144 days. In 3 cases the decrease in the size of tumors located in both liver and the other metastases also was seen. Every case developed high grade fever, but an antifebrile was effective. Otherwise severe side effects were not seen. These results indicated that intermittent arterial infusion immunochemotherapy was feasible for the treatment of metastatic liver cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[EEG data filing system with personal computer and magneto-optical disc].

We established a new computerized EEG filing system, in which an EEG machine was connected to an EEG filing unit which consisted of a personal computer with a 32 bit CPU, 18 channel analog -to-digital and digital-to-analog converters, and a magneto-optical disc driver. This system has the following merits. The system was space-saving, the space required to store the EEG data, being only 1/500 of that required for storing EEG record. Though the system had two independent EEG filing units, our original file configuration enabled us to have access to all of the recorded EEG data anytime for more than 10 years. The system enabled us to display EEG data continuously on the high resolution CRT, just as if turning the page of an EEG record paper, and through the quick scanning, enabled us to view the entire EEG pattern. Furthermore, the system enabled us to conduct reliable digital analysis for EEG data by entering the EEG data without artifacts into a data processor after confirmation on the display. In the system, we used data files with the MS-DOS operating system. This enabled us to analyze the data obtained by a personal computer operating on other systems, by transferring the data to a floppy disc operating on our system. Our EEG filing system allows quick access to data as well as mass data storage.

Electroencephalography↗

[Basal ganglia germinoma treated with interstitial brachytherapy; case report].

A case of primary intracranial germinoma in the left basal ganglia treated with interstitial brachytherapy was reported. A 15-year-old boy was referred to our hospital for evaluation of right hemiparesis. A CT scan showed a slightly hyperdense mass with multiple cystic low density in the left basal ganglia. The mass was heterogeneously enhanced after intravenous administration of contrast material. T1 weighted image showed a slightly hyperintense mass with cystic components and the mass was heterogeneously enhanced with Gd-DTPA. T2 weighted MR image showed a mixed intensity mass and peritumoral edema. Stereotactic needle biopsy and implantation of 3 catheters for interstitial brachytherapy were performed simultaneously using BRW CT guided stereotactic apparatus. After the histological diagnosis was confirmed to be two cell pattern germinoma, 9 iridium-192 seeds were inserted into the catheters and maintained for 10 days to give 35Gy of irradiation at the tumor periphery. Subsequent CT scans showed marked tumor regression and the clinical symptoms were improved. Germinoma originating in the basal ganglia is rare and hard to diagnose previous to biopsy. Histological confirmation is essential before initiation of treatment because germinoma is commonly thought to be radiosensitive tumor. The interstitial brachytherapy enables selective irradiation of the tumor and actually causes no complications such as bone marrow suppression or cerebral atrophy. The neuroradiological findings, especially of CT scan and MRI, were presented and the strategy for treatment of germinoma in basal ganglia was discussed.

Adolescent↗