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Biomedical subjects

H Tomoda

Publications and source records attributed to H Tomoda.

At least 163 records · Page 9Linked to original sources
PubMed1991

Purpactins, new inhibitors of acyl-CoA:cholesterol acyltransferase produced by Penicillium purpurogenum. III. Chemical modification of purpactin A.

Acylated derivatives of the C-1' and/or C-11 hydroxy group(s) of penicillide were synthesized and their inhibitory activity against acyl-CoA:cholesterol acyltransferase (ACAT) was studied. Introduction of long acyl group into either or both hydroxy residue(s) decreased the inhibitory activity. A small acyl moiety such as acetyl or n-butyryl at the C-1' hydroxy group is responsible for potent inhibitory activity against ACAT. The 1'-O-acetyl-11-O-tetrahydropyranyl derivative (11-O-2''-tetrahydropyranylpurpactin A) showed high selectivity (cytotoxic dose vs. effective dose) in a cell assay using J774 macrophages.

Animals↗
PubMed1991

Hepatic recurrence not prevented with low-dosage long-term intraportal 5-FU infusion after resection of colorectal liver metastasis.

Seventeen patients with colorectal cancer metastatic to the liver underwent hepatic resection. For five we prescribed adjuvant therapy which included intraportal mitomycin C (MMC) and 5-fluorouracil (5-FU) and consecutive oral administrations of tegafur (N1-(2'-tetrahydrofuryl)-5-fluorouracil), in an attempt to reduce recurrences in the liver. Intraportal chemotherapy consisted of low-dosage, long-term 5-FU infusion, 40 days at 250 mg/day, and a 10 mg bolus injection of MMC at the start and the end of continuous 5-FU infusion. With regard to postoperative events in patients given the infusion therapy, there was no hepatotoxicity or hematologic toxicity, no mechanical complications and no pain or vomiting. Two of five patients given infusion therapy and six of 12 not given the therapy died within 5 years after surgery. There was recurrence in the liver in two patients given infusion therapy and in four not given the therapy. Although low-dosage, long-term intraportal chemotherapy is a safe treatment given hopefully to prevent hepatic recurrence, we found no beneficial effect.

Adult↗
PubMed1990

A rectal carcinoid tumor of less than 1 cm in diameter with lymph node metastasis: a case report and a review of the literature.

We report herein, a patient with a rectal carcinoid tumor of less than 1 cm in diameter with lymph node metastasis, and discuss a surgical policy for these lesions with reference to other such cases reported in the literature. A 40 year old female was admitted with a rectal mass and colonoscopy revealed a subpedunculated lesion, 1 cm in diameter, with a depression in its tip. A diagnosis of carcinoid was made by biopsy and transsacral excision performed. The excised specimen revealed a subpedunculated lesion measuring 7 X 6 X 6 mm with a central depression. The tumor was histologically confined to the submucosa but lymphatic invasion with pararectal lymph node involvement was observed. A radical proctectomy was thus performed. The incidence of metastasis from rectal carcinoids with a diameter of 1 cm or less is very low ranging from 1.5 to 3.4 per cent, and it therefore seems that most lesions of 1 cm or less in diameter can be treated by local excision alone. Thus, although it is recommended that local excision be performed first to determine the extent of spread, lymphatic vessel invasion and lymph node metastasis, radical surgery is indicated if lymphatic invasion or nodal involvement is present, even when muscle invasion is absent.

Adult↗
PubMed1990

Mechanism of action of atpenin B on Raji cells.

Atpenin B, a new antifungal antibiotic produced by Penicillium sp. FO-125, inhibited the growth of Raji cells (IC50, 30 microM). The incorporation of [14C]leucine and [3H]thymidine into Raji cells was inhibited by atpenin B with IC50 values of 0.10 and 0.12 microM, respectively. The incorporation of [14C]palmitate into the cells was not inhibited but its incorporation into lipid fractions was inhibited by atpenin B (IC50, 0.13-0.24 microM). Studies on the site of atpenin B action demonstrated that atpenin B decreases the cellular adenosine 5'-triphosphate (ATP) level in Raji cells with IC50 value of 0.020 microM, suggesting the inhibition of ATP-generating system by atpenin B.

Acyltransferases↗
PubMed1990

The structures of atpenins A4, A5 and B, new antifungal antibiotics produced by Penicillium sp.

The structures of atpenins A4, A5 and B, new antifungal antibiotics produced by Penicillium sp., have been deduced to be I, II and III, respectively, on the basis of spectroscopic and 1H and 13C NMR spectral data. The molecular structure of atpenin A4 with absolute configurations was finally confirmed to be 2'S,4'S,5'S-5,6-dimethoxy-4-hydroxy-5'-chloro-2',4'- dimethyl-1'-oxoheptyl-2-hydroxypyridine (I') by the single crystal X-ray crystallographic analysis. The absolute configurations of atpenins A5 and B were also expected to be 2'S,4'S,5'R-II (II') and 2'S,4'R-III (III'), respectively.

Antifungal Agents↗
PubMed1990

Method of search for microbial inhibitors of mevalonate biosynthesis using animal cells.

A new screening method for specific inhibitors of mevalonate biosynthesis was established using Vero cells, an animal cell line. The cultures selected were those which inhibited the growth of Vero cells in the EAGLE's minimum essential medium supplemented with 2% calf serum (2% CS-MEM) but lacked inhibitory activity against the growth of cells in 2% CS-MEM supplemented with 1 mM mevalonate. By this screening method, inhibitors of the two enzymes involved in mevalonate biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and HMG-CoA reductase, were selected from about 11,000 soil isolates. The beta-lactone 1233A, a fungal metabolite, was found to be the first naturally occurring compound which inhibits HMG-CoA synthase specifically and strongly. Monacolins K and J, inhibitors of HMG-CoA reductase, were also detected and identified.

Actinomycetales↗
PubMed1990

In vitro augmentation of macrophage-activating-factor release from peripheral blood cells of cancer patients by a DNA fraction from Mycobacterium bovis BCG.

Effect of a DNA-rich fraction from Mycobacterium bovis BCG (MY-1) on the macrophage-activating-factor (MAF)-activity release from peripheral blood lymphocytes (PBL) of patients with benign diseases and patients with gastric cancer or colorectal cancer was studied in vitro. The MAF activity was augmented by the addition of 10 micrograms/ml of MY-1 in many cases. Augmentation of the MAF activity in benign disease, gastric cancer and colorectal cancer in stages I to III was observed in five of six cases, eight of 10 cases and five of eight cases, respectively. The activity of MY-1-induced MAF was partially abolished by the treatment with monoclonal anti-interferon-gamma (IFN-gamma) antibody. These results suggest that MY-1 augments MAF-activity release from PBL by inducing IFN-gamma and other MAF-like substances.

DNA, Bacterial↗
PubMed1989

Temperature effect on endocytosis and exocytosis by rabbit alveolar macrophages.

Endocytosis of 125I-mannose-bovine serum albumin (BSA) and exocytosis of 125I-mannose-poly-D-lysine by rabbit alveolar macrophages were examined as a function of temperature. A plot for total ligand uptake (cell-associated ligand plus degraded ligand) versus time shows a single inflection point at 20 degrees C. Ligand degradation does not occur below 20 degrees C. Internalization of surface-bound 125I-mannose-BSA is negligible below 10 degrees C. The rate constant for internalization increases dramatically above 20 degrees C: 0.02 min-1 at 20 degrees C, 0.05 min-1 at 25 degrees C, 0.13 min-1 at 30 degrees C, and 0.29 min-1 at 35 degrees C. 125I-Mannose-N-acetyl-poly-D-lysine preloaded in lysosomes is exocytosed in a temperature and time-dependent fashion. Even at lower temperatures (2-10 degrees C), secretion of 125I-mannose-N-acetyl-poly-D-lysine was detected, indicating that movement of lysosomal content to plasma membrane and beyond cannot be suppressed at these temperatures. Thus, the temperature dependence of exocytosis of an 125I-labeled ligand is quite different from that of endocytosis, suggesting that the two processes are controlled by different mechanisms. Stimulation of secretion of preloaded 125I-mannose-N-acetyl-poly-D-lysine by mannose-BSA was more pronounced at lower temperatures with a sharp inflection point at 10 degrees C. These findings suggest that endosomes containing newly internalized mannose-BSA interact with the exocytosis pathway and enhance secretion of 125I-mannose-N-acetyl-poly-D-lysine from lysosomes.

Animals↗
PubMed1989

The policy of surgery for small carcinoid tumors of the rectum.

In this report, we discuss the current policy of surgery for small carcinoid tumors of the rectum, with reference to our own cases and also to those reported in the literature. Ten cases of rectal carcinoid tumors were surgically treated at the National Kyushu Cancer Center over a period of sixteen years and three months. The tumors ranged in size from 0.2 to 1.0 cm, with an average of 0.5 cm, and all were confined to the submucosa. The lesions were treated by local excision in eight patients and by low anterior resection in the other two cases, where transanal or transsacral excision was considered difficult. No lymph node involvement was found in these two cases. All patients are alive and well without recurrence, after an average follow-up time of three years and six months. According to the literature, the incidence of metastasis from rectal carcinoid tumors smaller than 1 cm is very low, ranging between 1.7 to 3.4 per cent, and it therefore seems that most such lesions can be treated by local excision alone. If, however, any muscle invasion or lymphatic vessel invasion is demonstrated, then radical surgery is recommended.

Adult↗
PubMed1989

Binding site of cerulenin in fatty acid synthetase.

An antibiotic cerulenin, (2R, 3S)-2,3-epoxy-4-oxo-7,10-trans,trans- dodecadienamide, irreversibly inhibits fatty acid synthetase from Saccharomyces cerevisiae. Three moles of cerulenin were bound to 1 mol of the enzyme with concomitant loss of its activity. Pretreatment of the enzyme with iodoacetamide reduced the amount of cerulenin bound to the enzyme. Since iodoacetamide is known to specifically bind to the cysteine residue on the condensing reaction domain, cerulenin is considered to bind to the same domain. Tryptic digestion of the [3H] cerulenin-treated enzyme gave a radioactive peptide; its amino acid composition was Asx 1, Thr 1, Ser 1, Glx 2, Pro 1, Gly 1, Ala 1, Val 1, Ile 1, and Leu 2. This composition included all the amino acids of the condensing reaction site (Thr-Pro-Val-Gly-Ala-Cys) previously reported by Kresze et al. (Eur. J. Biochem., 79, 181 [1977] except for Cys. When the enzyme was treated with [3H]cerulenin and digested successively with trypsin and carboxypeptidase P, a [3H] cerulenin-cysteine adduct was isolated as the sole product. This was identified with the adduct chemically synthesized from non-labeled cerulenin and cysteine, and its structure was elucidated by 1H-, 13C-NMR, and fast atom bombardment mass spectrometry. These results indicate that cerulenin, forming a hydroxylactam ring, reacts at its epoxide carbon (C-2 position) with the SH-group of the cysteine residue in the condensing reaction domain of yeast fatty acid synthetase.

Amino Acids↗
PubMed1989

[Relations of intracardiac dimensions as measured by echocardiography and plasma atrial natriuretic peptide levels in various cardiovascular diseases].

The correlation between the plasma atrial natriuretic peptide (ANP) levels and echocardiographically measured atrial and ventricular dimensions was studied in various cardiovascular diseases. A total of 107 patients (valvular heart disease 27, cardiomyopathy 11, ischemic heart disease 17, hypertension 42, congenital heart disease 2, and normal 8) were studied. None of the patients had overt signs of heart failure, though 22 of them had atrial fibrillation. Left ventricular end-diastolic and end-systolic diameters, ejection rate and end-diastolic posterior wall thickness were measured by M-mode echocardiography. Maximal left and right atrial diameters and right ventricular end-diastolic diameter were measured by the apical four-chamber view. Following echocardiographic evaluation and blood pressure measurement, blood sampling was performed via the antecubital vein into a tube containing aprotinin and the samples were analyzed by radioimmunoassay. There was no significant correlation between ANP level and heart rate, systemic blood pressure, left ventricular end-diastolic and end-systolic diameters, ejection fraction, posterior wall thickness or right ventricular end-diastolic diameter. The most probable reason for the insignificant relationships was that the correlation varied according to the underlying cardiovascular diseases; e.g., correlation between ANP level and left ventricular diameter was significantly positive in mitral regurgitation, while it was significantly negative in hypertrophic cardiomyopathy. There was a significant correlation between ANP level and the maximal right (r = 0.40, p less than 0.001) or left atrial diameter (r = 0.57, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Development of a cancer of the large bowel following radiotherapy for cancer of the uterine cervix].

Eight patients with a colorectal cancer, following radiotherapy for a cervical cancer have been analyzed. A total of 9 lesions in the large bowel were found. Four were located in the rectum. The average interval between radiation and the diagnosis of a second tumor was 9 years and 6 months. Four patients had had a post-irradiation interval of more than 10 years. In 7 resected specimens, histologic alterations were seen, such as atrophy or the erosion of the mucosal layer around the tumor. Radiotherapy may have contributed to the development of the colorectal cancer in some of these patients. Thus, attention should be paid to monitoring patients who have received radiotherapy for a cervical cancer, since the development of a colorectal cancer after pelvic radiotherapy may occur.

Aged↗
PubMed1988

Central vs peripheral nerve conduction. Before and after treatment of subacute combined degeneration.

Central and peripheral nerve conduction was studied in two patients with subacute combined degeneration by using the short-latency somatosensory evoked potentials and the peripheral nerve conduction study during treatment with cyanocobalamin. Before the treatment, somatosensory evoked potentials with median nerve stimulation were normal, but those with peroneal nerve stimulation revealed prolonged central conduction indicating dysfunction within the posterior column. Peripheral sensory and motor nerve action potentials were reduced with normal or slightly reduced conduction velocity. After treatment, marked shortening of the central conduction time (by 24% and 31%, respectively) was observed with mild or no recovery of peripheral nerve action potentials. These physiologic findings suggest that the main pathologic changes in the central nervous system may be demyelination in the posterior column in addition to axonal degeneration in the peripheral nerve. The former was responsive to treatment but the latter was poorly responsive to treatment. Sensory symptom in subacute combined degeneration appears to be, at least partially, attributed to the spinal cord lesion.

Adolescent↗
PubMed1988

Surgery for colorectal cancer in elderly patients--a comparison with younger adult patients.

Between 1972 and 1986, 668 patients without familial polyposis coli underwent surgery for colorectal cancer at the National Kyushu Cancer Center. Among these, there were 85 patients aged 75 years and older, and 39 patients aged 39 years and younger. The older patients tended to have a higher frequency of less advanced disease (stage I-III) and the progression of cancer in the older patients appeared to be relatively mild. The operative mortality rate of the older patients was as low as 1.2 per cent, which was almost identical to that of the younger adults (0 per cent), being 16.7 per cent for emergency operations, whereas it was 0 per cent for elective operations. The five-year survival curve of the older patients with curative resections was significantly better than that of those with noncurative resections. There was no significant difference in the cancer-related five-year survival curves between the older and younger patients with curative resections. Surgery for colorectal cancer in elderly patients should therefore not be restricted on the basis of chronological age alone.

Adult↗
PubMed1988

Experimental study on myocardial salvage by coronary thrombolysis and mechanical recanalization.

Salvage of the ischemic myocardium by coronary thrombolysis and mechanical recanalization (simulated angioplasty) was studied in a canine experimental model of acute myocardial infarction induced by coronary occlusive thrombus at the left anterior descending coronary artery. Forty-four open-chest dogs divided into three groups were studied. Group I (n = 15, control group) was observed for 6 hours following the onset of infarct. In group II (n = 14, thrombolysis group), thrombolysis was obtained by intravenous administration of urokinase 2 hours after the onset of infarct. In group III (n = 15, mechanical recanalization group), simulated angioplasty was performed 2 hours after infarct. Coronary reperfusion was continued for 4 hours in groups II and III. The areas of left ventricular risk and infarct were measured by double staining methods with Evans blue dye and triphenyl tetrazolium hydrochloride. There were no significant differences in control blood flow and risk area in the three groups. Myocardial infarct area/risk area was 65 +/- 3% in group I, 45 +/- 1% in group II, and 35 +/- 2% in group III (group I vs II, p less than 0.001; group II vs III, p less than 0.001). Restored coronary blood flow in the left anterior descending artery was 8 +/- 1 ml/min in group II and 14 +/- 1 ml/min in group III (p less than 0.001). The data suggest that coronary mechanical recanalization is more effective than thrombolysis in salvaging the ischemic myocardium in the early phase of myocardial infarction, most probably because coronary blood flow is better restored by mechanical recanalization.

Angioplasty, Balloon↗
PubMed1988

Intracoronary thrombodynamics in the early phase of acute myocardial infarction.

Intracoronary thrombodynamics in the early phase of acute myocardial infarction were studied in an experimental canine model. Intracoronary thrombus was precipitated at the mock ruptured atheromatous plaque consisting of cholesterol and collagen. (1) Myocardial infarction occurred in 10 and sudden death in 2 secondary to intracoronary thrombotic occlusion in 15 control experiments. (2) Pretreatment with an antiplatelet drug, ticlopidine, significantly reduced the incidence of myocardial infarction and sudden death (7/18, 39% vs. 12/15, 80%, p less than 0.05). (3) During the period when intracoronary thrombus was precipitated, a transient reduction in aortic pressure induced by nitroglycerin resulted in rapid progression of intracoronary thrombotic occlusion in 7 of 21 animals and in 5 of 17 animals treated with nitroprusside. The terminated coronary blood flow could be restored by raising coronary perfusion pressure with methoxamine in 5 of 10 cases with coronary thrombotic occlusion. (4) Cigarette smoking appeared to accelerate the completion of coronary thrombotic occlusion. (5) Sudden death occurred in 12 of 43 models without pharmacological intervention during coronary thrombotic occlusion associated with myocardial dysynergy. Six sudden deaths occurred within 10 min and 9 within 30 min following coronary thrombotic occlusion. Postmortem complete autolysis of intracoronary thrombus was observed in 24% and partial thrombolysis in 28%.

Animals↗