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Biomedical subjects

H Tomoda

Publications and source records attributed to H Tomoda.

At least 109 records · Page 6Linked to original sources
PubMed1994

Interrelationship between estradiol and tamoxifen responses for clinical breast carcinoma cells cultured on contact-sensitive plates.

An in vitro assay system for predicting the estradiol (E2) sensitivity of clinical cancer cells was applied to 54 patients with breast carcinoma to compare the responses to E2 and tamoxifen (TAM) with the estrogen receptor (ER) status. We found that 18 of the 35 cases in the ER-positive group and 6 of the 19 cases in the ER-negative group were stimulated by E2. It is suggested that ER status alone can not predict the response of cultured cells to E2 in clinical breast cancer. Cell growth of 11/35 (31%) of the ER-positive cases and that of 8/19 (42%) of the ER-negative cases was inhibited by E2. Since the cases inhibited by E2 could not be distinguished by ER status alone, an assay system based on a quantitative proliferative response was considered necessary. There were 20 (83%) cases of inhibition by TAM among the 24 stimulated by E2. Only 18/35 (51%) of the ER-positive group exhibited growth inhibition by TAM. In our (CSP) assay, 20 (83%) of the 24 cases stimulated by E2 were inhibited by TAM, 10 (91%) of the 11 E2-insensitive cases were insensitive to TAM and 13 (68%) of the 19 cases inhibited by E2 were stimulated by TAM. In short, TAM response and E2 response tended to be inversely related (43/54 = 80%, P < 0.01). Furthermore, the E2-response rate showed a good correlation with the TAM-response rate (R2 = 0.825). These results indicate the feasibility of predicting individual tumor responses to either E2 or TAM by using CSPs.

3T3 Cells↗
PubMed1994

Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl-CoA synthase inhibitors: 2-oxetanones with a meta-substituent on the benzene ring in the side chain.

Isosteric side chain analogs of 3a were synthesized and tested for inhibitory activities towards 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and upon cholesterol production in Hep G2 cells and in mouse liver. It became clear that the lipophilic substituent on the aromatic ring and the terminal hydrophilic group in the side chain were important in the enhancement of activity. 4-[2-(3-n-Hexyloxyphenyl)ethyl]-3-hydroxy-methyl-2-oxetanone (5a) showed equivalent inhibitory activity in vivo to that of 1233A.

Animals↗
PubMed1994

Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl-CoA synthase inhibitors: 2-oxetanones with a side chain mimicking the extended structure of 1233A.

Structural analogs of 1233A, a microbial metabolite inhibiting 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) synthase, were designed and synthesized. The 2-oxetanone moiety was left intact. All analogs prepared were tested for inhibition of HMG-CoA synthase activity and sterol synthesis in mouse liver and for effect on serum triglyceride levels. Of these analogs, trans-4-[2-[3-(7-carboxy-2- naphthyl)phenyl]ethyl]-3-hydroxymethyl-2-oxetanone (4a) showed the highest inhibitory activity in vitro, and also had in vivo inhibitory activity without causing any increase in triglyceride level.

Animals↗
PubMed1994

Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitors: 2-oxetanones with a side chain mimicking the folded structure of 1233A.

To mimic the folded side chain conformation of 1233A (1), which is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitor, 1233A analogs with aromatic rings in the side chain were synthesized. The 2-oxetanone moiety was kept intact. Among 1233A and its synthetic analogs, trans-3-hydroxymethyl-4-[2-(7-methoxycarbonyl-1-naphthyl)ethyl]-2-oxe tanone (23) showed the highest HMG-CoA synthase inhibitory activity in vitro. The structure-activity relationship at the side chain is discussed.

Animals↗
PubMed1994

Pyripyropenes, novel inhibitors of acyl-CoA:cholesterol acyltransferase produced by Aspergillus fumigatus. I. Production, isolation, and biological properties.

Aspergillus fumigatus FO-1289, a soil isolate, was found to produce a series of novel inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Four active compounds, named pyripyropenes A, B, C and D, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography, ODS column chromatography and preparative HPLC. Pyripyropenes A, B, C and D show very potent ACAT inhibitory activity in an enzyme assay system using rat liver microsomes with IC50 values of 58, 117, 53 and 268 nM, respectively.

Animals↗
PubMed1994

Pyripyropenes, novel inhibitors of acyl-CoA:cholesterol acyltransferase produced by Aspergillus fumigatus. II. Structure elucidation of pyripyropenes A, B, C and D.

The structures of pyripyropenes A, B, C and D, novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors, were determined mainly by spectroscopic studies including various NMR measurements. Pyripyropenes have a common structure which consists of pyridine, alpha-pyrone and sesquiterpene moieties. One of the three O-acetyl residues in the sesquiterpene moiety of pyripyropene A is replaced with an O-propionyl residue in pyripyropenes B, C and D.

Aspergillus fumigatus↗
PubMed1994

Arohynapenes A and B, new anticoccidial agents produced by Penicillium sp. Taxonomy, fermentation, and structure elucidation.

Penicillium sp. FO-2295, a water isolate, was found to produce a series of new anticoccidial compounds. Two active compounds, designated arohynapenes A and B, were isolated from the fermentation broth of the producing strain by solvent extration and preparative HPLC. Arohynapene A was deduced to be (2E,4E)-5-(5-hydroxy-2,6,8-trimethyl-5,6,7,8-tetrahydronaphtale ne)-2,4- pentadienoic acid, and arohynapene B was (2E,4E)-5-(2-hydroxymethyl-6,8-dimethyl-5,6,7,8-tetrahydronapht alene)-2,4- pentadienoic acid. Arohynapenes inhibited the growth of Eimeria tenella in an in vitro assay using BHK-21 cells as a host. No schizont in the cells was observed at concentrations ranging above 35.0 microM and 7.0 microM for arohynapenes A and B, respectively.

Coccidiostats↗
PubMed1994

Cytosaminomycins, new anticoccidial agents produced by Streptomyces sp. KO-8119. I. Taxonomy, production, isolation and physico-chemical and biological properties.

Streptomyces amakusaensis KO-8119, a soil isolate, was found to produce a series of new anticoccidial compounds. Four active compounds, designated as cytosaminomycins A, B, C and D, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and preparative HPLC. Cytosaminomycins inhibited the growth of Eimeria tenella in an in vitro assay system using primary chicken embryonic cells as a host. No schizont in the cells was observed at concentrations ranging from 0.3 to 0.6 microgram/ml for cytosaminomycins A, B and C, and at 2.5 micrograms/ml for cytosaminomycin D.

Aminoglycosides↗
PubMed1994

Cytosaminomycins, new anticoccidial agents produced by Streptomyces sp. KO-8119. II. Structure elucidation of cytosaminomycins A, B, C and D.

Structures of novel anticoccidial antibiotics, cytosaminomycins A, B, C and D, were elucidated by NMR studies. Cytosaminomycins were shown to be nucleoside antibiotics related to oxyplicacetin. Their carboxylic acid moieties bonded to the cytosine residue were different from that of oxyplicacetin. The carboxylic acids contained in cytosaminomycins A, B, C and D were (E)-3-(methylthio)acrylic acid, 4-methylaminobenzoic acid, 3-methylcrotonic acid, and tiglic acid, respectively.

Aminoglycosides↗
PubMed1994

[Effect of adjuvant chemotherapy for patients with early gastric cancer].

Effects of adjuvant chemotherapy following curative resection were evaluated in patients with early gastric cancer. According to postoperative chemotherapy, seven hundred and thirty-one patients were divided into four groups as follows. MMC+FT group: those who received mitomycin C and tegafur; MMC group: those receiving MMC; FT group: those given tegafur or 5-FU; NC group: those who never received chemotherapy. Postoperative recurrence was observed in 25(3.4%) of the 731 patients. Relationships between rates of recurrence or survival with clinicopathological findings were assessed among the four groups. In cases with cancer cell invasion of the intralesional veins, recurrence tended to occur less in the groups given postoperative chemotherapy, compared to the NC group. When a positive venous invasion was determined, rates of recurrence in the MMC+FT, MMC, FT and NC groups, were 7.4, 0, 0 and 35.7%, respectively. On the other hand, in relation to other clinicopathological findings, no differences were observed in rates of recurrence among those groups. As for the survival rate, no differences were observed in the clinicopathological findings among the four groups. These findings indicate that adjuvant chemotherapy may contribute to prevention of postoperative recurrence in patients with early gastric cancer, especially in cases with positive venous invasion.

Adult↗
PubMed1993

Prognostic significance of flow cytometric analysis of DNA content in colorectal cancer: a prospective study.

We prospectively analyzed the tumor DNA content by flow cytometry in 100 patients who underwent a curative resection for colorectal cancer between August 1989 and May 1992 in order to evaluate the prognostic significance of DNA ploidy and the DNA index (DI). Patients with aneuploid tumors were found to have a significantly shorter disease-free survival than those with diploid tumors (P = 0.014). In addition, patients who had tumors with a DI greater than 1.6 had a significantly shorter disease-free survival than those who had tumors with a DI of less than 1.6 (P = 0.0001). After stratification by stage, this association was only seen in Dukes' stage C disease (P = 0.0065). Cox's regression analysis demonstrated that the DI (below or above 1.6) rather than DNA ploidy was an important independent predictor of disease-free survival. These results suggest that the DI rather than DNA ploidy provides us with important prognostic information in patients undergoing curative surgery for colorectal cancer.

Adenocarcinoma↗
PubMed1993

Intrahepatic splenosis mimicking a liver tumor.

A rare case of ectopic splenic tissue in the liver is presented which mimicked a liver tumor. It is considered that some splenic tissue was seeded in the liver during the splenectomy that the patient underwent 23 years ago. Computed tomography (CT), magnetic resonance imaging (MRI), and angiographic features of this lesion were almost indistinguishable from those of other liver tumors.

Choristoma↗
PubMed1993

The effects of physostigmine on the response characteristics of the cat visual evoked potential.

Steady-state pattern visual evoked potentials were recorded from the surface of the cat primary visual cortex before and after the intravenous administration of physostigmine, an agent that blocks the enzyme responsible for the breakdown of synaptically released acetylcholine. Under pentobarbital anesthesia, physostigmine increased the amplitude and changed the phase of the second response harmonic of the visual evoked potential, whereas the amplitude and phase of the fourth harmonic were not affected. These effects persisted for 15 to 45 minutes and were blocked by prior treatment with scopolamine or atropine. In addition, scopolamine or atropine administered 5 to 10 minutes after physostigmine returned the visual evoked potential to the baseline state. In comparison, when nitrous oxide was used, physostigmine caused a marked reduction in visual evoked potential amplitude, an effect that was reversed by subsequent atropine. These results indicate that the cholinergic system influences the visual evoked potential via a muscarinic pathway and that this influence is strongly affected by the anesthetic regimen used.

Acetylcholine↗
PubMed1993

Plasma endothelin-1 in acute myocardial infarction with heart failure.

Endothelin-1 is a potent vasoconstricting substance that may aggravate circulatory dysfunction in acute myocardial infarction. In 59 patients with acute myocardial infarction peripheral venous blood was sampled, and endothelin-1 was measured by radioimmunoassay. Hemodynamic measurements were performed with a flow-directed thermodilution catheter in 16 patients. Plasma endothelin-1 levels in Killip's classes were as follows: group I (no heart failure, n = 25), 1.97 +/- 0.69 pg/ml; group II (heart failure, n = 16), 2.74 +/- 1.02 pg/ml; group III (pulmonary edema, n = 13), 4.54 +/- 1.17 pg/ml; and group IV (cardiogenic shock, n = 5), 8.91 +/- 3.16 pg/ml (normal control group, n = 12: 1.51 +/- 0.39 pg/ml). There were significant correlations between the plasma endothelin-1 level and mean right atrial pressure (r = 0.554; p < 0.05), mean pulmonary artery pressure (r = 0.589; p < 0.02), and cardiac index (r = -0.534; p < 0.05). There were closer correlations between plasma endothelin-1 level and mean pulmonary artery wedge pressure (r = 0.678; p < 0.005) and total pulmonary vascular resistance (r = 0.831; p < 0.001). These results indicate that endothelin-1 is elevated in accordance with cardiac and pulmonary circulatory distress in patients with acute myocardial infarction, which may further aggravate circulatory dysfunction.

Catheterization, Swan-Ganz↗