Search PubMed⌕ Search

Biomedical subjects

H Tomoda

Publications and source records attributed to H Tomoda.

At least 73 records · Page 4Linked to original sources

Superoxide dismutase activity as a predictor of myocardial reperfusion and salvage in acute myocardial infarction.

We attempted to predict successful myocardial reperfusion and salvage in acute myocardial infarction (AMI) by using measurements of plasma superoxide dismutase (SOD), a plasma free-radical scavenger, activity. Forty-nine patients with AMI were studied within 6 hours of symptoms onset. In group 1 (n = 26), primary percutaneous transluminal coronary angioplasty (PTCA) was undertaken, and plasma SOD activity was measured for 8 hours by the nitrite method. Left ventricular (LV) angiography was assessed before and 3 months after PTCA by computer LV contraction analysis. In group 2 (n = 23), TPA was infused intravenously over a 60-minute period, and plasma SOD activity was measured before and immediately after TPA infusion. In group 1, occluded coronary arteries were successfully dilated in 24 of 26 patients, and plasma SOD activity increased from 3.20 +/- 0.17 microns/ml to 4.66 +/- 0.29 microns/ml at 1 hour after PTCA (p < 0.001), returning to the basal level by 8 hours after PTCA. Plasma SOD activity did not significantly change patients with unsuccessful PTCA or those with the no-reflow phenomenon. The maximal increase in plasma SOD activity was significantly correlated with the grade of improvement in LV contraction (r = 0.852, p < 0.001). In group 2, the sensitivity and specificity of predicting coronary recanalization was 86% and 89%, respectively. In conclusion, myocardial reperfusion and salvage in AMI can be predicted by changes in plasma SOD activity.

Aged↗

A clinicopathological study of asymptomatic gastric cancer.

The clinicopathological profiles of 419 patients with asymptomatic gastric cancer (AGC) first detected by gastric screening, were reviewed and compared with those of the 1727 patients with symptomatic gastric cancer (SGC). The incidence of AGC increased gradually and has amounted to 30% of the total resected cases in recent years. About 75% of AGC cases were of early cancer and 84% were negative for lymph node metastases. In contrast, only 33% of SGC cases were of early cancer and 57% were node positive. Curative resection was done in 97% of AGC and 75% of SGC. The cumulative 5 and 10 year survival rates of patients with curatively resected AGC were 85.2% and 72.2%, respectively, while those for patients with SGC were 66.8% and 55.4%. These data demonstrated that most patients with asymptomatic gastric cancers could expect a curative resection, i.e. have a better clinical outcome, than those with symptomatic cancer.

Adult↗

Analysis of Ki-ras codon 12 mutations in the duodenal juice of patients with pancreatic cancer.

BACKGROUND & AIMS: Point mutations of the Ki-ras gene at codon 12 have been frequently identified in pure pancreatic juice of patients with pancreatic cancer in studies examining pancreatic cancer tissues. The aim of this study was to examine mutations of the Ki-ras codon 12 in the duodenal juice collected from patients with various pancreatic disorders. METHODS: The duodenal juice was collected through a Dreiling tube installed in the duodenum during a secretin test. Analysis of the Ki-ras mutations was performed using the enriched polymerase chain reaction--single-strand conformation polymorphism technique. RESULTS: Point mutations were detected in 12 of 19 patients with pancreatic cancer; of the 12 patients, 10 had ductal tubular adenocarcinoma and 2 intraductal papillary adenocarcinoma. Mutational patterns included GAT (n = 4), GTT (n = 3), CGT (n = 1), and double mutations of GTT and GAT (n = 3) and GAT and CGT (n = 1). In 41 patients with benign pancreatic disorders, a point mutation was detected in only 1 patient with chronic pancreatitis. CONCLUSIONS: Analysis of the Ki-ras codon 12 mutations in the duodenal juice is useful in the diagnosis of pancreatic cancer.

Base Sequence↗

Morphogenesis of the brain in larval and juvenile Japanese eels, Anguilla japonica.

We compared the morphology, including relative volumes (RV), of some brain regions in leptocephalus larvae (10-30 mm in total length), glass eels (elvers), young, and immature pre-adults of the Japanese eel Anguilla japonica. The external brain shape of the leptocephali gradually changes from a laterally compressed one to a depressed elongated one. These changes are fundamentally due to biased growth of the telencephalon and optic tectum. The dramatic brain transformation progresses until the juvenile stage and culminates in an adult-type brain arrangement, with a developed cerebellum and eminentia granularis and a much more flattened appearance. The RVs of brain regions closely related to somatic sensory functions are quite different in larvae and juveniles. The larvae possess larger optic tecta and smaller chemo- and mechanosensory regions than the juveniles. The RV of the olfactory bulb increases, and that of the optic tectum decreases, until the adult stage, unlike the condition in a pelagic fish, Pagrus major, suggesting that adult eels are inferior to pelagic fishes in visual perception. In contrast, the brain morphology of the larvae suggests that they are equipped with a well-developed visual system, while the functional significance of the system still remains a mystery. It might be important for feeding, orientation and diurnal vertical migration of the larvae.

Anguilla↗

Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups.

Four hydroxyl groups of pyripyropenes have been modified and evaluated for their ability to inhibit microsomal acyl-CoA:cholesterol acyltransferase (ACAT) activity in vitro and to lower cholesterol absorption in vivo in a cholesterol-fed hamster. 7-O-n-Valeryl derivative (8c) improved the in vitro ACAT inhibitory activity (IC50 = 13 nM) about 7 times better than pyripyropene A. Introduction of methanesulfonyl group at 11-hydroxyl group (17a) increased both in vitro activity (IC50 = 19 nM) and in vivo efficacy (ED50 = 10 mg/kg).

Animals↗

Chemical modification and structure-activity relationships of pyripyropenes. 2. 1,11-Cyclic analogs.

A series of 1,11-cyclic analogs of pyripyropene A were prepared. Replacement of the 1,11-acyl groups of pyripyropenes with 1,11-cyclic acetals effectively improved in vitro acyl CoA:cholesterol acyltransferase (ACAT) inhibitory activity. Especially noteworthy is benzylidene acetal analog 35, the most potent inhibitor (IC50 = 5.6 nM) among the derivatives prepared so far, which showed 16 times more potent inhibitory activity than pyripyropene A.

Animals↗

New isochromophilones VII and VIII produced by Penicillium sp. FO-4164.

New isochromophilones VII and VIII were isolated from the culture broth of Penicillium sp. FO-4164. The structures were elucidated as 6H-2-benzopyran-6,8(7H)-dione, 5-chloro-3-(3',5'-dimethyl-1',3'-heptadienyl)-1,7,8a-trihydro-7, 8a-dihydroxy-7-methyl-7-acetate for isochromophilone VII and 6H-2-benzopyran-6-one,5-chloro-3-(3',5'-dimethyl-1', 3'-heptadienyl)-1,7,8,8a-tetrahydro-7,8-dihydroxy-7-methyl-8-acetate for isochromophilone VIII. Isochromophilones VII and VIII inhibited diacylglycerol acyltransferase activity with IC50 values of 20.0 and 127 microM and acyl-CoA: cholesterol acyltransferase activity with IC50 values of 24.5 and 47.0 microM, respectively.

Acyltransferases↗

Xanthoquinodin B3, a new anticoccidial agent produced by Humicola sp. FO-888.

Xanthoquinodin B3, a new component of anticoccidial xanthoquinodins, which was detected in the culture broth of Humicola sp. FO-888, was isolated by heat treatment of the xanthoquinodins complex. Structural elucidation indicated that xanthoquinodin B3 has the same heterodimer of xanthone- and anthraquinone-derived monomers as other xanthoquinodins. Schizont formation of monensin-resistant Eimeria tenella in BHK-21 cells was inhibited by xanthoquinodin B3 at concentrations greater than 0.035 microM.

Animals↗

Pyripyropenes, novel ACAT inhibitors produced by Aspergillus fumigatus. IV. Structure elucidation of pyripyropenes M to R.

Six new pyripyropenes, M to R, were isolated from the ethyl acetate extracts of the jar fermentation broth of Aspergillus fumigatus FO-1289-2501. Structural elucidation indicated that all the pyripyropenes have the same pyridino-alpha-pyrone sesquiterpene core as pyripyropenes A to L. Among them pyripyropene M showed the most potent inhibition against acyl-CoA : cholesterol acyltransferase activity with an IC50 value of 3.80 microM in rat liver microsomes, but pyripyropenes N to R showed moderate inhibitory activity (IC50 11.0 approximately 78.0 microM).

Animals↗

[Continuous hepatic arterial infusion chemotherapy with low-dose CDDP plus 5-FU for liver metastases from colorectal carcinoma].

Seven patients with unresectable liver metastases from colorectal carcinoma were treated with low-dose CDDP plus 5-FU continuous hepatic arterial infusion chemotherapy. A hepatic artery catheter was placed into the gastroduodenal artery at laparotomy or percutaneously placed into the proper hepatic artery via left subclavian artery. Through an injection port placed beneath the skin, 5-FU (300 mg/m2/day) was continuously infused for 5 days; CDDP (6 mg/m2/day) was infused for 5 successive days a week. One cycle consisted of 4 weeks. The response rate was 71% (1 CR, 4 PR, 2 NC). The CEA level decreased in all cases. The median survival was 17 months. Major toxicities were abdominal pain and appetite loss due to extrahepatic perfusion of the drugs. Failure in maintaining the catheter was a problem in most cases. The pharmacokinetic study demonstrated high hepatic extraction of CDDP and 5-FU (40% and 90%, respectively). These results suggest that continuous hepatic arterial infusion chemotherapy with low-dose CDDP plus 5-FU is effective for patients with unresectable liver metastases from colorectal carcinoma.

Adult↗

Spinal and parachordal neurons in the eel leptocephali, Anguilla japonica revealed by labeling with a fluorescent dye.

The spinal and parachordal neurons innervating the trunk muscles and skin in the Japanese eel leptocephali, Anguilla japonica, were retrogradely labeled with a fluorescent dye, DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate). The spinal motoneurons innervating the trunk muscles were located in the medioventral part of the spinal cord and were divided into two populations on the basis of their soma sizes and position. The sensory neurons were labeled in the well-developed dorsal root ganglia, that were situated just peripheral to the meeting of the dorsal and ventral roots. Presumable postganglionic sympathetic neurons were also labeled in the sympathetic ganglia which were located ventrally to the notochord. Thus, the spinal and parachordal neurons innervating the trunk muscles and skin were firstly identified in the anguilliform leptocephalus.

Anguilla↗

Immunohistochemical analysis of p53 in colorectal cancer regarding clinicopathological correlation and prognostic significance.

The overexpression of the tumor suppressor gene p53 was investigated immunohistochemically in 144 cases of primary colorectal cancer and in 8 cases with cancer in the corresponding metastatic lymph nodes. Abnormalities in p53 expression were found in 36 cases (25%) of the 144 primary cancer cases. In addition, p53-positive tumors were found to metastasize frequently to the lymph nodes, as compared to p53-negative tumors (61.1% vs. 41.7%, P = 0.0428). p53 staining was identical in 7 of 8 (87.5%) cases in primary and metastatic lesions. When the DNA content of the tumor was determined by flow cytometry, the DNA index (mean +/- SD) was significantly higher in p53-positive tumors than in p53-negative tumors (1.57 +/- 0.38 vs. 1.39 +/- 0.37, P = 0.012). Therefore, the immunohistochemical data of p53 in colorectal cancer may help in potentially predicting metastatic spread to the lymph nodes.

Colonic Neoplasms↗

Flow cytometric analysis of the DNA content in primary and metastatic lesions of colorectal cancer.

We investigated and compared the DNA content between primary and metastatic lesions from 30 colorectal cancer cases. The findings were only diploid in 2 cases (6.7%) and only aneuploid in 18 cases (60.0%). On the whole, the DNA ploidy agreed in 20 cases (66.7%) between both lesions. In the 18 cases with only aneuploid tumors in both lesions, the DNA index tended to be larger in the metastatic lesions than in the primary lesions. In contrast, a variation in the DNA ploidy was observed in 10 cases (33.3%). These findings show that DNA ploidy tends to remain stable during metastasis in many cases of colorectal cancer, although the DNA index did tend to be larger in metastatic lesions than in primary lesions. The existence of intertumoral heterogeneity in the DNA ploidy also shows that specimens should be investigated from both lesions in order to obtain more accurate information on the tumor and its biological behavior.

Adenocarcinoma↗

Parvocellular and magnocellular contributions to visual evoked potentials in humans: stimulation with chromatic and achromatic gratings and apparent motion.

Psychophysical evidence suggests that two major parallel pathways, the parvocellular (P) and the magnocellular (M) pathways, exist in humans. We herein report that responses specific to the P and M systems can be recorded in human visual evoked potentials (VEPs) by using the appropriate stimuli. The onset of isoluminant chromatic (red-green) and high contrast achromatic sinusoidal gratings were used for stimulating the P-system. A chromatic stimulation evoked a characteristic negative wave (N1) with peak latencies around 120 msec. The amplitude showed an inverse U-shaped function as a function of spatial frequency with a peak at 2 c/deg. In contrast, VEPs to achromatic (black-white) gratings showed different spatial frequency characteristics with a peak at 5.3 c/deg. By varying the luminous intensity ratio between the red and green gratings, N1 was found to reach a maximum during isoluminant stimulation. An apparent motion display was used for stimulating the M-system. The speed of alternation (i.e., the interstimulus interval (ISI)) was varied to record both the transient and steady-state VEPs. Transient VEPs showed triphasic waves with the major positive peak (P1) at around 120 ms. Steady-state VEPs were quasi-sinusoidal waveforms, depending on the ISI, and were quite stable across all subjects. There was a also high correlation between the motion threshold and the VEP amplitude. The above observations indicate that characteristic potentials may distinguish between these two parallel visual systems in humans. Thus, the combined use of isoluminant color and high contrast achromatic gratings and an apparent motion display is considered to be useful for evaluating both systems electrophysiologically.

Adolescent↗

Cytotoxicity of CPT-11 for gastrointestinal cancer cells cultured on fixed-contact-sensitive plates.

The cytotoxicity of SN-38, the major metabolite of CPT-11 (7-ethyl-10-[4-(1-piperidino)-1- piperidino]carbonyloxycamptothecin, was compared among gastrointestinal carcinomas of every organ, and between primary and metastatic lesions of every organ-originated gastrointestinal carcinoma, by an in vitro anticancer drug sensitivity test using fixed-contact-sensitive plates. The rates of cases having a high response (percent survival 75% or lower) to SN-38 but a low response (percent survival above 75%) to cisplatin, mitomycin C (MMC), adriamycin (ADM) and 5-fluorouracil (5-FU) were 14.6, 19.4, 15.6 and 27.0%, respectively. While, the rates of cases having a high response to cisplatin, MMC, ADM and 5-FU but a low response to SN-38 were 7.3, 2.8, 9.4 and 13.5%, respectively. Each of the former rates were higher than each of the latter rates. In particular, the former rate for MMC was significantly higher than the latter rate (p = 0.04). Two cases with colon cancer showed a high response only to SN-38. The percent survival of primary lesions in colon cancer was significantly lower than that in stomach cancer. The rates of hepatocellular carcinoma cases having a high response to SN-38 but a low response to cisplatin, MMC, ADM and 5-FU were 16.7, 16.7, 0 and 25%, respectively. Only one case had a high response to 5-FU but a low response to SN-38. The percent survival of metastatic lesions in pancreatic cancer was significantly lower than that of primary lesions. From this study, we recommend the further clinical trial of CPT-11 for colon and hepato-cellular cancers.

Animals↗

Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. I. Production, isolation and biological properties.

A series of new acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors termed terpendoles were isolated from the culture broth of a fungal strain FO-2546 which was proposed to belong to a new genus designated as Albophoma yamanashiensis. Among four structurally related terpendoles, terpendole C showed the most potent ACAT inhibitory activity with an IC50 value of 2.1 microM in an in vitro enzyme assay, followed by terpendoles D (IC50: 3.2 microM), A (15.1 microM) and B (26.8 microM). Evaluation of their ACAT inhibition in the cell assay using J774 macrophages indicated that terpendole D exhibited the highest specificity (cytotoxicity vs. ACAT inhibition) among microbial ACAT inhibitors we discovered so far.

Animals↗

Pyripyropenes, Novel ACAT inhibitors produced by Aspergillus fumigatus. III. Structure elucidation of pyripyropenes E to L.

Eight new pyripyropenes, E to L, were isolated from the culture broth of Aspergillus fumigatus FO-1289-2501 selected as a higher producer by NTG mutation. Structural elucidation indicated that all the pyripyropenes have the same pyridino-alpha-pyrone sesquiterpene core as pyripyropenes A to D. Among them, pyripyropene L showed the most potent inhibition against acyl-CoA: cholesterol acyltransferase (ACAT) activity with an IC50 value of 0.27 microM in rat liver microsomes.

Animals↗