Biomedical subjects

H Tomoda

Publications and source records attributed to H Tomoda.

At least 55 records · Page 3Linked to original sources

PubMed1998

Family aggregation of carcinoma of the hypopharynx and cervical esophagus: special reference to multiplicity of cancer in upper aerodigestive tract.

The role of family history in the multiple occurrence of cancer in the upper aerodigestive tract (UADT) remains unclear. The family histories of close relatives were examined in 167 patients with either hypopharyngeal or cervical esophageal cancer (PhCe cancer) and in 167 control subjects with benign diseases. The odds ratio for PhCe cancer was 2.6 in relation to family history of UADT cancers. Based on the family histories of close relatives, 167 cases with PhCe cancer were divided into 3 groups (Group I, 18 cases with a family history of UADT cancer; Group II, 37 cases with a family history of other cancers; Group III, 112 cases with no family history of any cancers). The mean age of the cases in group I was 59.4, which was younger than in group III (64.2). Second primary squamous-cell carcinomas in the UADT were more frequently recognized in group I (39%) than in group III (11%). However, no differences were observed in the smoking and drinking habits of male patients between each group. These results thus suggest that a family history of UADT cancers appears to be associated with the multiple occurrence of UADT cancers as well as the development of PhCe cancer.

Aged↗

PubMed1998

Submucosal gastric cancer with lymph node metastasis.

BACKGROUND AND OBJECTIVES: The intraoperative assessment of lymph node metastasis of gastric cancer remains difficult and the characteristics of recurrence after gastrectomy are not well known regarding submucosal cancer. METHODS: We examined 452 patients with submucosal gastric cancer and compared the clinicopathologic features as well as recurrence patterns between the 71 cases with lymph node metastasis (group I) and the 381 without it (group II). RESULTS: The mean tumor sizes were 44.8 and 33.5 mm, respectively (P < 0.01). The incidences of lymphatic invasion and vascular invasion were 91.5% (65/71) and 45.1% (32/71) in group I, which were significantly higher than those in group II (36.7 and 14.2%, 140/381 and 54/381, respectively, P < 0.01). A total of 21 patients (4.6%, 21/452) experienced recurrence after undergoing a gastrectomy and hematogenic recurrence was the most frequent type of recurrence (2.0%, 9/452). However, in group I, lymphatic recurrence was most frequently observed (7.0%, 5/71), and it was more frequent than in group II (0.3%, 1/381, P < 0.01). The median intervals between gastrectomy and recurrence were 34.5 and 64.0 months in groups I and II, respectively (P < 0.05). CONCLUSIONS: The submucosal cancer with larger size, lymphatic invasion, and vascular invasion has high risks for lymph node metastasis. Furthermore, a strict follow-up for lymphatic as well as hematogenic recurrence is important for the patients with node positive submucosal cancer, especially within 5 years after operation.

Female↗

PubMed1998

DNA index as a significant predictor of recurrence in colorectal cancer.

PURPOSE: To clarify the prognostic significance of the DNA content in cases of colorectal cancer, we investigated the relationship between the DNA content, as determined by the DNA ploidy or DNA index, and disease-free survival. RESULTS: This study included 201 cases that were treated by curative surgery between 1989 and 1995 at our hospital. 68 were diploid and 133 were aneuploid. The mean DNA index of these tumors was 1.42. Recurrence occurred in 30 cases (14.9 percent). Tumor site, venous invasion, Dukes stage, DNA ploidy (diploid or aneuploid), and a DNA index (less than or greater than 1.4) correlated well with disease-free survival. A multivariable analysis suggested the DNA index to be a stronger predictor than DNA ploidy. Patients with aneuploid tumors had shorter disease-free survival than those with diploid tumors (P = 0.011), especially in Dukes Stage C cases (P = 0.0209). Patients with a DNA index greater than 1.4 also had a shorter disease-free survival than those with a DNA index less than 1.4 (P < 0.001), especially in Dukes Stage C cases (P = 0.0033). CONCLUSIONS: The DNA index value (less than or greater than 1.4) seems to be a stronger predictor than DNA ploidy (diploid or aneuploid), and the combination of Dukes stage, tumor site, and a DNA index is, therefore, considered to be clinically valuable in predicting recurrence in cases of colorectal cancer.

Aged↗

PubMed1998

Plasma soluble P-selectin in acute myocardial infarction: effects of coronary recanalization therapy.

P-selectin is translocated from platelets and endothelial cells to initiate the first step in a sequence of events leading to the adherence of leukocytes, possibly inducing reperfusion injury and the no-reflow phenomenon in acute myocardial infarction (AMI). This study was undertaken to investigate plasma P-selectin in AMI patients undergoing coronary recanalization therapy. A total of 40 patients were studied: 20 patients with AMI who underwent coronary recanalization by direct percutaneous transluminal coronary angioplasty (PTCA), 10 patients with AMI who underwent thrombolytic therapy by tissue-type plasminogen activator (TPA), and 10 patients with stable angina pectoris who underwent elective PTCA. Blood samples were obtained from systemic arteries before and immediately after PTCA or thrombolytic therapy. Plasma-soluble P-selectin was measured by enzyme immunoassay. Plasma P-selectin was significantly higher in AMI than in stable angina pectoris (176.6 +/- 12.9 ng/mL vs 91.4 +/- 9.5 ng/mL, p<0.001). Plasma P-selectin did not change significantly as a result of elective PTCA in patients with stable angina (from 91.4 +/- 9.5 ng/mL to 87.9 +/- 7.9 ng/mL). Plasma P-selectin was decreased by direct PTCA in all of the 20 patients with AMI (from 176.2 +/- 17.7 ng/mL to 141.7 +/- 12.6 ng/mL; p<0.001, paired t-test), whereas it was increased by thrombolysis using TPA in nine of the 10 AMI patients (from 177.4 +/- 17.2 ng/mL to 248.8 +/- 17.3 ng/mL, p<0.005). Increased P-selectin activity in AMI appeared to be attenuated by direct PTCA, but augmented by thrombolysis, possibly due to direct stimulatory effects of TPA on P-selectin expression. This may lead to less favorable results in salvaging the ischemic myocardium by thrombolytic than mechanical coronary recanalization therapy in AMI.

Angina Pectoris↗

PubMed1998

Erabulenols, inhibitors of cholesteryl ester transfer protein produced by Penicillium sp. FO-5637. I.Production, isolation and biological properties.

Penicillium sp. FO-5637, a soil isolate, was found to produce a series of inhibitors of cholesteryl ester transfer protein (CETP). Novel active compounds, designated erabulenols A and B, were isolated from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography and HPLC. Erabulenols A and B inhibit human CETP activity with IC50 values of 47.7 and 58.2 microM in an in vitro assay system containing 200 microM BSA, respectively.

Anti-Bacterial Agents↗

PubMed1998

Erabulenols, inhibitors of cholesteryl ester transfer protein produced by Penicillium sp. FO-5637. II. Structure elucidation of erabulenols A and B.

Structures of erabulenols A and B, novel fungal inhibitors of cholesteryl ester transfer protein were elucidated by spectroscopic studies including various NMR measurements. Erabulenols consist of a phenalenone skeleton and a 1,2,2-trimethyltetrahydrofuran moiety in common. Erabulenol B possesses an additional 2,6-dihydroxy-5-methyl-3-methylketonyl benzyl moiety. The absolute stereochemistry at the C-2' position of erabulenol A was deduced as S by comparison of the optical rotation with that of other related compounds.

Carrier Proteins↗

PubMed1997

Xanthohumols, diacylglycerol acyltransferase inhibitors, from Humulus lupulus.

A methanol extract of hops of Humulus lupulus (L.) showed inhibitory activity against rat liver diacylglycerol acyltransferase (DGAT). From DGAT inhibitory activity-guided fractionation, two chalcones were isolated. One was identified as xanthohumol and the other was found to be a new product designated xanthohumol B. The structure of xanthohumol B was shown to be 6-[3,4-dihydro-3,5-dihydroxy-7-methoxy-2,2-dimethyl-2H-benzo[b]pyrano ]- 3-(4-hydroxyphynyl)-2-propen-l-one by spectroscopic studies including various NMR measurements. Xanthohumol and xanthohumol B inhibited DGAT activity with IC50 values of 50.3 and 194 microM in rat liver microsomes, respectively. They showed preferential inhibition of triacylglycerol formation in intact Raji cells, indicating that they inhibit DGAT activity preferentially in living cells.

Acyltransferases↗

PubMed1997

Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety.

Structure-activity relationships of the pyridine-pyrone moiety in pyripyropene A (1), a potent acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor of fungal origin, were studied. Several kinds of aromatic or hetero ring substituents for the pyridine moiety were synthesized using unique degradation reaction, following by gamma-acylation. All the six synthesized analogs decreased the inhibitory activity with 20 to 200 times larger IC50 values than that of 1. Furthermore, the pyridine-pyrone substituent also dramatically decrease the inhibitory activity. Thus, the pyridine-pyrone moiety is important for eliciting potent ACAT inhibition.

Enzyme Inhibitors↗

PubMed1997

[Pyrimidine nucleoside phosphorylase activity, 5-fluorouracil concentration and thymidylate synthase inhibition rate in colorectal cancer after oral administration of 5'-doxifluridine].

To assess the mechanism of the anticancer effect of doxifluridine (5'-DFUR), a clinicopharmacological study was performed. So far, no comparative study has been reported between the thymidylate synthase (TS) inhibition rate and the 5-FU concentration in colorectal cancer after oral administration of 5'-DFUR. In 37 patients with colorectal cancer, 5'-DFUR was administered orally/preoperatively (800 mg/day x more than 4 days before operation and 300 mg on the day of operation). The mean total dosage was 6.9 g. Specimens of tumor and normal intestinal tissue were obtained 4.4 hours on average after final administration. The TS inhibition rate as well as the 5-FU concentration and the activity of pyrimidine nucleoside phosphorylase (PyNPase) were analyzed in both tissues. The PyNPase activity was significantly higher in the tumor tissue than in the normal tissue (137.9 +/- 10.8 vs. 31.0 +/- 4.7 micrograms FU/mg protein/hr, p < 0.0001). The 5-FU concentration was also significantly higher in the tumor tissue than in the normal tissue (101.3 +/- 30.6 vs. 23.2 +/- 5.5 ng/g, p = 0.024). The TS inhibition rate correlated with the 5-FU concentration in the tumor tissue (r = 0.527, p = 0.047). These findings suggest that the TS inhibition rate may be an index of the anticancer effect of 5'-DFUR in colorectal cancer.

Adenocarcinoma↗

PubMed1997

Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety

Structure-activity relationships of the pyridine-pyrone moiety in pyripyropene A (1), a potent acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor of fungal origin, were studied. Several kinds of aromatic or hetero ring substituents for the pyridine moiety were synthesized using unique degradation reaction, following by gamma-acylation. All the six synthesized analogs decreased the inhibitory activity with 20 to 200 times larger IC50 values than that of 1. Furthermore, the pyridine-pyrone substituent also dramatically decrease the inhibitory activity. Thus, the pyridine-pyrone moiety is important for eliciting potent ACAT inhibition.

Journal Article↗

PubMed1996

Possible prevention of postangioplasty restenosis by ascorbic acid.

In this preliminary study to assess the possibility of using ascorbic acid to prevent post-percutaneous transluminal coronary angiography (PTCA) restenosis, the incidence of restenosis was significantly less in 50 patients receiving 500 mg/day of oral ascorbic acid than in 51 control patients. Thus, ascorbic acid, a potent natural antioxidant, appeared to be possibly effective in attenuating post-PTCA restenosis.

Adult↗

PubMed1996

Lactacystin increases LDL receptor level on HepG2 cells.

Low density lipoprotein (LDL) receptor expression is regulated by proteolysis of transcription factors, sterol regulatory element binding proteins. To investigate the involvement of proteasome in this regulatory process, the effect of lactacystin, a specific proteasome inhibiton of microbial origin, was tested on LDL receptor expression on HepG2 cells. The addition of lactacystin to the cell culture increased the number of LDL receptors, indicating that proteasome plays a down-regulatory role in LDL receptor expression.

Acetylcysteine↗

PubMed1996

Potential advantages in therapeutic index of OK-432 ointment to abdominal skin over systemic applied in a mouse model.

A mixture of OK-432 powder and an ointment base, lanolin, was applied to mouse abdominal skin. After application of the mixture of 5 KE OK-432 and 0.2g lanolin, the leucocyte count and IL-b content in the abdominal cavity increases to up to 3.6 x 10(6) cells and 1.4 ng, respectively. INF-gamma content in the cavity after application of a mixture of 10 KE OK-432 and 0.2 g lanolin also increases, although not after application of the 5 KE OH-432 mixture of dorsum subcutaneous injection of a saline solution of 5 KE OK-432. These results indicate that an application of OK-432 mixed in lanolin to the mouse abdomen is able to exert an influence on the immunomodulatory effect in the abdominal cavity. The concentrations of IL-6 in serum after applying the ointment mixture, and subcutaneous of intraperitoneal injection of the saline solution of 5 KE OK-432, were <20, 370, and 430 pg/ml, respectively. After application of the ointment mixture of 5 KE OK-432, serum IL-6 did not increase. IL-6 levels in the abdominal cavity after 5 KE OK-432 ointment of subcutaneous injection increases to up to 1.4 and 2.1 ng/cavity. From these results, the immunomodulatory systemic response of OK-432 brought about by applying OK-432 ointment to the abdominal skin is lower than that brought about by injecting OK-432 subcutaneously. Therefore, it is thought that application of OK-432 ointment might be most suitable for potentiating local immune response.

Abdominal Muscles↗

PubMed1996

Complete inhibition of human immunodeficiency virus Gag myristoylation is necessary for inhibition of particle budding.

Myristoylation of human immunodeficiency virus (HIV) Gag protein is essential for virus particle budding. Two reactions are involved; activation of free myristate to myristoyl-CoA and transfer of the myristoyl residue to the Gag N-terminal glycine. We have investigated the effects of triacsin C, an inhibitor of long chain acyl-CoA synthetase, on release of HIV Gag virus-like particle (VLP) produced using the recombinant baculovirus system. First, inhibition of acyl-CoA formation by triacsin C was confirmed using the membrane fractions of insect Sf9 cells as an enzyme source. Second, when HIV Gag protein was expressed in the presence of triacsin C (0-48 microM), Gag myristoylation was inhibited in a dose-dependent manner. Budding of Gag VLP, however, did not follow similar inhibition kinetics but appeared unaffected up to 24 microM, yet was completely abolished at 48 microM when the myristoylation of Gag protein was also completely inhibited. The "all-or-none" inhibition of Gag VLP budding suggests that although inhibition of acyl-CoA synthetase blocks the production of myristoylated Gag protein, only complete inhibition of Gag myristoylation prevents VLP budding. Thus, relatively few myristoylated Gag molecules are sufficient for plasma membrane targeting and VLP budding.

Acyl Coenzyme A↗

PubMed1996

Clinical manifestations in patients with hereditary nonpolyposis colorectal cancer.

The clinical manifestations of 1,042 Japanese patients with nonpolyposis colorectal cancer who underwent a resection between 1972 and 1992 at the National Kyushu Cancer Center were examined. Hereditary nonpolyposis colorectal cancer (HNPCC) was found in 39 (3.7%) patients. Some characteristic findings in HNPCC cases included early age of onset, a preponderance of right colon cancers, an increased frequency of colorectal cancers, and a favorable survival. Metachronous (postoperative) colorectal cancers developed significantly more often in cases with HNPCC than in those without (12.8% vs. 1.8%, P = 0.0001). Metachronous (postoperative) extracolonic cancers tended to develop more often in cases with HNPCC than in those without (10.2% vs. 3.5%, P = 0.053). In cases with HNPCC, the mean interval between the initial surgery and the diagnosis of the second cancer was 61 months (range; 12-153 months). These findings thus indicate the importance of routine and long-term follow-up to identify any second lesions, especially in patients with HNPCC.

Adolescent↗

PubMed1996

Human VEPs to isoluminant chromatic and achromatic sinusoidal gratings: separation of parvocellular components.

To extract the responses specific to the parvocellular system (color vision and form perception) in humans, visual evoked potentials (VEPs) in response to the onset of isoluminant chromatic (red-green) and achromatic (black-white) sinusoidal gratings were recorded in 15 young adults. Chromatic stimulation evoked a characteristic negative wave (N1) with peak latencies around 120 msec. The amplitude resembled an inverse U-shaped function against the spatial frequency with a peak at 2 c/deg. In contrast, VEPs to achromatic gratings showed different spatial frequency characteristics with a peak at 5.3 c/deg. With variations in the luminous intensity ratio between the red and green gratings, N1 was seen to respond maximally to isoluminant stimulation. These results indicate that the combined use of isoluminant chromatic and achromatic patterns could stimulate the parvocellular system selectively in humans.

Adult↗

PubMed1996

Advantages and safety of local treatment with MMC/Beriplast P for cancer tumors.

To target the treatment of small points of cancer, Beriplast P, already used clinically as a physiological tissue adherent drug carrier, was mixed with the anticancer drug, mitomycin C (MMC). In this in vitro study, MMC did not release quickly from the clot of MMC/Beriplast P. The antitumor effect of this mixture was examined for its effect on cancer growth. In one series of experiments, tumor tissues were inoculated with MMC/100 microliters Beriplast P and in another series, MMC/100 microliters Beriplast P was injected into tumors at a weight of 300 mg. In the first series of experiments, tumor tissue treated with 0.3 mg MMC/100 microliters Beriplast P was replaced with plasma cells and lymphocytes, and no viable cancer cells could be found. In the second series, MMC/100 microliters Beriplast P delayed tumor growth, and the survival of Balb/c mice injected with 0.08 mg MMC/100 microliters Beriplast P was significantly longer than that of mice injected with 0.08 mg MMC/100 microliters saline solution (P = 0.026). In addition, the abdominal aorta, vena cava, and intestine around the area of treatment with 1.6 mg MMC/100 microliters Beriplast P were not damaged. These results indicate that the mixture of Beriplast P and MMC is more effective than MMC solution alone in the local treatment of residual cancer.

Animals↗

PubMed1996

Normal variability of the amplitude and phase of steady-state VEPs.

The present study quantifies the amplitude and phase variability of steady-state VEPs (S-VEPs) and compares this variability between subjects and between individual runs. The S-VEPs were recorded repeatedly in 14 normal subjects with varying spatial and temporal frequencies of sinusoidal gratings; 6 spatial frequencies (range 0.5-8.0 c/deg) with 3 temporal frequencies (4, 6 and 8 Hz) were used. A total of 75 responses were averaged and analyzed by the Fourier method. Four recordings were obtained in each spatio-temporal combination. In general, the phase data showed small inter- and intrasubject variability. As anticipated, the amplitude data showed a large degree of intersubject variability, although the intrasubject variability was very small. In addition, in some stimulus conditions the inter- and intrasubject variability increased, which thus suggested the existence of an optimal spatio-temporal combination. Therefore, these stimulus parameters should be taken into consideration when S-VEPs are applied in clinical practice.

Adult↗