Search PubMed⌕ Search

Biomedical subjects

H Tomoda

Publications and source records attributed to H Tomoda.

At least 91 records · Page 5Linked to original sources
PubMed1995

Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. II. Structure elucidation of terpendoles A, B, C and D.

Structures of terpendoles A, B, C and D, novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors, were determined by spectroscopic studies. All terpendoles consist of diterpene and indole moieties in common. Terpendoles A, C and D possess an additional isoprenyl unit via oxygen atom(s) of their diterpene moieties. The relative stereochemistries of terpendoles C and D were confirmed by NOE experiments and X-ray crystallographic analysis.

Anti-Bacterial Agents↗
PubMed1995

Fudecalone, a new anticoccidial agent produced by Penicillium sp. FO-2030.

Penicillium sp. FO-2030, a soil isolate, was found to produce a new anticoccidial compound. The active compound, designated fudecalone, was isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and preparative HPLC. The structure of fudecalone was elucidated to be 3,3a,6,6a,7,8,9,10-octahydro-1-hydroxy-4,7,7-trimethyl-1H-naphtho[1,8a- c]furan-6-one mainly by spectroscopic studies including various NMR measurements. The anticoccidial activity using cell systems indicated that schizont formation of monensin-resistant Eimeria tenella was completely inhibited by fudecalone at concentrations more than 16 microM.

Animals↗
PubMed1995

Isochromophilones III-VI, inhibitors of acyl-CoA:cholesterol acyltransferase produced by Penicillium multicolor FO-3216.

New azaphilones named isochromophilones III-VI were isolated from the culture broth of Penicillium multicolor FO-3216 as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT). Their structures were elucidated by NMR and other spectroscopic analyses. The IC50 values of isochromophilones III, IV, V and VI for ACAT activity in an enzyme assay using rat liver microsomes were calculated to be 110, 50, 50 and 120 microM, respectively.

Animals↗
PubMed1995

Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. III. Production, isolation and structure elucidation of new components.

Eight new components of terpendoles E to L were isolated and characterized from the culture broth of Albophoma yamanashiensis using a different production medium. All the structures were elucidated by spectroscopic analyses including various NMR experiments, indicating that all the terpendoles have the same indoloditerpene core as terpendoles A to D. Terpendoles J, K and L showed the moderate inhibition against acyl-CoA: cholesterol acyltransferase (ACAT) activity with IC50 values of 38.8, 38.0 and 32.4 microM in rat liver microsomes, respectively. But terpendoles E-I showed weak activities (IC50 145-388 microM).

Animals↗
PubMed1995

Amidepsines, inhibitors of diacylglycerol acyltransferase produced by Humicola sp. FO-2942. I. Production, isolation and biological properties.

Humicola sp. FO-2942, a soil isolate, was found to produce a series of new inhibitors of diacylglycerol acyltransferase (DGAT). Three active compounds, designated amidepsines A, B and C, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography, ODS column chromatography and HPLC. Amidepsines inhibit DGAT activity with IC50 values of 10.2 approximately 51.6 microM in an enzyme assay system using rat liver microsomes. Amidepsines also showed specific inhibition of triacylglycerol formation in intact Raji cells, indicating that they inhibit DGAT activity in living cells.

Acyltransferases↗
PubMed1995

Amidepsines, inhibitors of diacylglycerol acyltransferase produced by Humicola sp. FO-2942. II. Structure elucidation of amidepsines A, B and C.

Structures of amidepsines A, B, C and D, diacylglycerol acyltransferase (DGAT) inhibitors, were determined by spectroscopic studies including various NMR measurements. They were elucidated as 2-hydroxy-4-[[2-hydroxy-4-[(2,4-dimethoxy-6-methylbenzoyl) oxy]6-methylbenzoyl]-oxy]-6-methylbenzoic acid N-alanine amide for amidepsine A, 2-hydroxy-4-[[2-hydroxy-4-[(2-hydroxy-4-methoxy-6-methylbenzoyl) oxy]6-methylbenzoyl]oxy]-6-methylbenzoic acid N-alanine amide for amidepsine B and 2-hydroxy-4-[[2-hydroxy-4-[(2-hydroxy-4-methoxy-6-methylbenzoyl) oxy]6-methylbenzoyl]oxy]-6-methylbenzoic acid N-valine amide for amidepsine C. Amidepsine D was identified with 2,4-di-O-methylgryphoric acid.

Acyltransferases↗
PubMed1995

[Antitumor effect of MMC mixed in Beriplast P].

We attempted to mix an anticancer drug. MMC, with a fibrinogen preparation, Beriplast P (B. P.). First, we examined how MMC was gradually released from its mixture. As the result, its release depended on the MMC concentration in B. P., and the release rate of 1.0 mg MMC from 100 microliters B. P. was 1.6 mg/30 min. Second, we examined the safety of the conjugated drug for normal tissue, because MMC is one of anticancer drugs causing serious damage to normal tissue. When the conjugation of 100 microliters B. P. and below 1.6 mg MMC was coated within one square centimeter, the drug was safe for the endothelium of artery and vein, and the intestinal wall. Third, we attempted an experiment on both the antitumor effect and the role of survival prolongation of the conjugated drug in a mouse carrying a malignant tumor. MMC conjugated with Beriplast P had a highly antitumor effect, which caused necrosis in the cancer cells in unstable conditions. Also, its conjugation drug could inhibit the growth of cancer cells in stable conditions, and prolonged the survival period. From these results, the mixture of MMC and B. P. was found to possess an MMC releasing effect, was safe for normal tissues, and showed high antitumor effect with prolongation of the survival period.

Animals↗
PubMed1995

[Immunopotentiation by OK-432 ointment to apply to the mouse abdominal skin].

The immunopotentiating effect of a streptococcal preparation, OK-432 (Picibanil), mixed with an ointment based Lanolin, was examined. The mixture was applied to mouse abdomen. The effect of OK-432 ointment was compared with those of OK-432 ip and sc. The leucocyte count in the abdominal cavity increased in 3.6 x 10(6) and 12.5 x 10(6) on the 3rd day after ointment application and ip injection of 5 KE OK-432, respectively. The result indicated that OK-432-Lanolin applied to the abdominal skin wall affected the abdominal cavity. IL-6 and IFN-gamma in the abdominal cavity increased in 1.4 ng and 9 ng, respectively, after applying 5 KE OK-432 ointment. From these results the treatment with OK-432 ointment on the abdominal skin exhibited an immunomodulatory effect on the abdominal cavity.

Abdomen↗
PubMed1995

[Chemoradiation therapy with low-dose carboplatin for squamous cell carcinoma of the esophagus].

Twenty-three patients with squamous cell carcinoma of the esophagus were treated with low-dose carboplatin and radiation therapy. Patients received 1.6 Gy-fractions daily; the total dose was 50-70 Gy for 14 unresectable cases, and 30-40 Gy for 8 resectable cases as preoperative irradiation. Carboplatin (30 mg/m2/day) was administered intravenously just before the irradiation; total dose was 1,100-2,000 mg for the unresectable cases, and 750-1,200 mg for the resectable cases. The response rate of the unresectable tumors was 86% (CR 5, PR 7, and NC 2). Three of the five CR patients were alive without recurrence for more than 2 years. The response rate of the resectable tumors was 75%. Although major toxicity was bone marrow suppression, there were no serious complications. These results suggest that this regimen is effective for patients with squamous cell carcinoma of the esophagus.

Aged↗
PubMed1995

Hepatic resection under in situ hemihepatic hypothermic perfusion with hepatoprotective agents.

Hepatectomy was performed under in situ right lobar hypothermic perfusion combined with hepatoprotective agents in six patients who had hepatocellular carcinoma and coexisting liver disease. Following occlusion of the right hepatic vein and the right portal pedicle, in situ cold perfusion was initiated using chilled Ringer's lactate infused through a cannula placed in the right main portal vein. The right superior segments were resected in a bloodless field. The liver was cooled to 22-26 degrees C for 40 to 80 minutes with no significant changes in systemic hemodynamics or body temperature. Postoperative liver functions showed no marked derangement; the mean peak GPT was 221 U and the mean peak total bilirubin 2.3 mg d/l. Local cooling minimizes the risk of ischemia/reperfusion injury in this very vulnerable population, yet gives the surgeon adequate time to perform a challenging resection in a bloodless field.

Aged↗
PubMed1995

[Analysis of DNA content in primary colorectal carcinoma and lung metastasis].

We analyzed DNA content of resected primary colorectal carcinoma and lung metastasis by flow cytometry. Of the 14 primary lesions, 5 cases showed diploid pattern, 9 cases aneuploid pattern. In contrast, 12 metastatic lung lesions of 19 showed diploid pattern and 7 lesions aneuploid pattern. DNA index of primary and metastatic lesions was 1.4 +/- 0.4 and 1.2 +/- 0.2, respectively (p = 0.08). In combination of DNA ploidy pattern between primary and metastatic lesions, there were 11 in which ploidy pattern was identical, 1 in which metastasis was aneuploid and primary was diploid, 7 in which metastasis was diploid and primary was aneuploid. Four year, survival rate from operation of metastasis was better in diploid pattern than in aneuploid pattern, but it was not significant. These results indicate that patients who have operative indication of metastasis from colorectal carcinoma have metastatic tumor which shows relatively good biological behavior (diploid tumors) and that there are heterogeneity of ploidy pattern between primary and metastatic lesions.

Adult↗
PubMed1994

Multiple occurrence of carcinoma in the upper aerodigestive tract associated with esophageal cancer: reference to smoking, drinking and family history.

Smoking and drinking habits as well as family history were examined in 143 men with esophageal cancer, including 30 who had associated second cancers of the upper aerodigestive tract (UADT) and 113 who did not. The risk of second cancers of UADT associated with the main lesions of the esophagus was evaluated, using odds ratios (ORs). As a result, the ORs of second cancers for current smoking and drinking were 5.3 and 7.6 respectively. The ORs significantly increased to 12.7 and 14.7 in heavy smokers and in heavy drinkers respectively. Furthermore, the risk of second cancer also significantly increased (8-fold) in patients who had close relatives with UADT cancer, compared to those without family history of any cancer. However, there were no differences in smoking or drinking habits regardless of family history. Our data thus suggest that a family history of UADT cancer as well as heavy smoking and drinking are clearly associated with multiple occurrence of UADT cancer. Therefore, careful and frequent examination for appearance of any second lesions are required for patients in these high-risk groups.

Aged↗
PubMed1994

Cerulenin-resistant mutants of Saccharomyces cerevisiae with an altered fatty acid synthase gene.

Cerulenin, an antifungal antibiotic produced by Cephalosporium caerulens, is a potent inhibitor of fatty acid synthase in various organisms, including Saccharomyces cerevisiae. The antibiotic inhibits the enzyme by binding covalently to the active center cysteine of the condensing enzyme domain. We isolated 12 cerulenin-resistant mutants of S. cerevisiae following treatment with ethyl methanesulfonate. The mechanism of cerulenin resistance in one of the mutants, KNCR-1, was studied. Growth of the mutant was over 20 times more resistant to cerulenin than that of the wild-type strain. Tetrad analysis suggested that all mutants mapped at the same locus, FAS2, the gene encoding the alpha subunit of the fatty acid synthase. The isolated fatty acid synthase, purified from the mutant KNCR-1, was highly resistant to cerulenin. The cerulenin concentration causing 50% inhibition (IC50) of the enzyme activity was measured to be 400 microM, whereas the IC50 value was 15 microM for the enzyme isolated from the wild-type strain, indicating a 30-fold increase in resistance to cerulenin. The FAS2 gene was cloned from the mutant. Sequence replacement experiments suggested that an 0.8 kb EcoRV-HindIII fragment closely correlated with cerulenin resistance. Sequence analysis of this region revealed that the GGT codon encoding Gly-1257 of the FAS2 gene was altered to AGT in the mutant, resulting in the codon for Ser. Furthermore, a recombinant FAS2 gene, in which the 0.8 Kb EcoRV-HindIII fragment of the wild-type FAS2 gene was replaced with the same region from the mutant, when introduced into FAS2-defective S. cerevisiae complemented the FAS2 phenotype and showed cerulenin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Flow cytometric analysis of variations in the DNA content of superficial and deep layers in colorectal cancer.

We investigated variations in the DNA content of multiple samples from both superficial and deep layers of tumors from 81 colorectal cancer cases. The findings were only diploid in 21 cases (25.9%) and only aneuploid in 49 cases (60.5%). On the whole, the DNA ploidy agreed in 70 cases (86.4%) between both layers. In the 49 cases with only aneuploid tumors in both layers, the DNA index (mean +/- SD) was 1.58 +/- 0.25 in the superficial layer and 1.59 +/- 0.25 in the deep layer, with the values being almost identical. In contrast, a variation in the DNA ploidy of 11 cases (13.6%) was observed. These findings show that DNA ploidy remains stable during tumor progression from the superficial into the deep layers in most cases of colorectal cancer. However, the existence of heterogeneity in the DNA ploidy also shows that several specimens should be collected from both layers before making a determination of DNA ploidy.

Adult↗
PubMed1994

Regional sympathetic denervation detected by iodine 123 metaiodobenzylguanidine in non-Q-wave myocardial infarction and unstable angina.

Previous studies have revealed that the sympathetic nervous system is more vulnerable to ischemia than the myocardium itself. Thus our study was undertaken to detect denervated myocardium in non-Q-wave myocardial infarction (MI) and unstable angina with iodine 123 metaiodobenzylguanidine (123I-MIBG), which can delineate myocardial sympathetic innervation. Eight patients with non-Q-wave MI and 12 with unstable angina were studied. Sequential 123I-MIBG and thallium-201 chloride (201TlCl) imaging and single-photon emission computed tomography (SPECT) were performed at rest 24 +/- 12 days after the last ischemic attack. Myocardial perfusion defect was not detected by 201TlCl in 4 of 8 patients with non-Q-wave MI, whereas 123I-MIBG SPECT imaging revealed defects corresponding to myocardial ischemic areas predicted by coronary angiography in all 8 patients. 123I-MIBG imaging revealed defects in 7 of 12 patients with unstable angina corresponding to coronary angiographic findings, whereas no myocardial perfusion defect was detected by 201TlCl imaging in any of them. In conclusion, 123I-MIBG SPECT is a sensitive method for detecting myocardium exposed to transient ischemia that cannot be detected by 201TlCl imaging.

3-Iodobenzylguanidine↗
PubMed1994

Selective delivery of a greater amount of methotrexate to regional lymph nodes using a new dosage formulation, methotrexate adsorbed on activated carbon particles, in rats.

A new dosage formulation (MTX-CH) comprising methotrexate (MTX) adsorbed onto a suspension of activated carbon particles was developed for the treatment of lymph node metastases. In vitro studies showed that activated carbon particles adsorbed a great amount of MTX. Subcutaneous injection of MTX-CH into the left hind foot pad of rats distributed a greater amount of MTX selectively to the regional lymph nodes (the left popliteal node and the para-aortic nodes) for a longer period of time than similar administration of MTX aqueous solution with a smaller amount of MTX distributed to the rest of the whole body.

Adsorption↗