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Biomedical subjects

H Hashizume

Publications and source records attributed to H Hashizume.

At least 163 records · Page 9Linked to original sources
PubMed1992

Synthesis of 1233A analogs and their inhibitory activity against hydroxymethylglutaryl coenzyme A synthase.

Simple and efficient syntheses of 1233A analogs were developed and the inhibitory activity of the analogs against hydroxymethylglutaryl coenzyme A (HMG-CoA) synthase was determined. Study of the structure-activity relationships revealed that not only the geometry in beta-lactone moiety but also the length of the carbon side chain is important for inhibitory activity against HMG-CoA synthase.

Animals↗
PubMed1992

An EDTA-KOH method to expose bone cells for scanning electron microscopy.

To observe bone cells by scanning electron microscopy (SEM), the mouse parietal bones were processed by decalcification with EDTA and digestion of collagen fibers with KOH to remove the bone matrix, in addition to the conventional preparation for SEM. The critical-point-dried specimens were split into two membranous pieces along the gaps formed by removing the bone matrix. By this method, osteoclasts showing full three-dimensional images of ruffled borders, osteoblasts showing special structures on the surfaces facing the bone matrix, and osteocytes extending many slender processes were clearly demonstrated in SEM. This new method may provide new viewpoints in bone cell biology.

Animals↗
PubMed1991

Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy.

This study was designed to determine the morphological correlate of chronic heart failure. Myocardial tissue from eight patients undergoing transplantation surgery because of end-stage dilated cardiomyopathy was investigated by electron microscopy and immunocytochemistry using monoclonal antibodies against elements of the cytoskeleton: desmin, tubulin, vinculin, and vimentin. The tissue showed hypertrophy, atrophy of myocytes, and an increased amount of fibrosis. Ultrastructural changes consisted of enlargement and varying shape of nuclei, numerous very small mitochondria, proliferation of T tubules, and accumulation of lipid droplets and glycogen. The most obvious ultrastructural alteration was the decrease of myofilaments, ranging from rarefication to complete absence of sarcomeres in cells filled with unspecified cytoplasm. Immunocytochemistry showed that desmin was localized at the Z lines. In diseased myocardium, the amount of desmin was increased, but it was disorderly arranged. Tubulin formed a fine network throughout the myocytes and was significantly increased in cardiomyopathic hearts. Vinculin, a protein closely associated with the cytoskeleton, occurred not only at the sarcolemma and the intercalated disc but also within the myocardial cells. Ultrastructural changes and alterations of the cytoskeleton were severe in about one third of all cells. About one third of all cells showed moderately severe changes, and the remaining cells were normal. Vimentin was present in the interstitial cells and was increased in relation to the increase of fibrosis. We conclude that the increase of fibrosis, the degeneration of hypertrophied myocardial cells, and the alterations of the cytoskeleton are the morphological correlates of reduced myocardial function in chronic heart failure.

Antibodies, Monoclonal↗
PubMed1990

Production of antikeratin autoantibodies by hybrid spleen cells of naive mice.

The mechanism of the occurrence of natural antikeratin antibodies in human sera was studied using hybrid spleen cells obtained from experimentally naive or from immunized mice. Antikeratin antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in 5.9-9.5% of the culture supernatants of fused spleen cells taken from naive mice. When mice were immunized with keratins, the number of supernatants containing antikeratin antibodies was increased to eight out of 51 (15.7%). When immunized with non-keratin materials such as activated human T cells, adult T-cell leukaemia cell lysates, and human T-cell lymphotropic virus type-I (HTLV-I), 16.7-20.8% of the supernatants were found to contain antikeratin antibodies by ELISA. The antikeratin antibodies in the supernatants showed cytoplasmic staining of keratinocytes in human as well as mouse skin by indirect immunofluorescence. The antibodies reacted with extracted human epidermal keratins by dot-blot and Western blot analysis. Most antikeratin antibodies in the supernatants did not show cross-reactivity with exogenous antigens used for immunization and vimentin-type intermediate-sized filaments. These findings demonstrate that B cells producing antikeratin antibodies are common in naive mice, and produce various types of antikeratin antibodies following specific activation with epidermal keratins and non-specific immunological stimuli.

Animals↗
PubMed1990

The familial occurrence of bullous mastocytosis (diffuse cutaneous mastocytosis).

We studied four patients (a mother, her two daughters, and her son) with bullous mastocytosis, or diffuse cutaneous mastocytosis, whose genetic inheritance suggested an autosomal dominant pattern. The clinical characteristics included extensive bullae, numerous urticaria, pruritus, flushing, and pseudolichenified skin over all body surfaces without systemic organ involvement. The histopathologic findings disclosed a pronounced accumulation of mast cells in the dermis. Electron microscopic studies of lesional skin obtained in infancy showed round or spindle-shaped mast cells with numerous fingerlike villous protrusions. The cytoplasmic granules varied in size and shape, and the appearance of degranulation was markedly noted. In the adult, most mast cells had markedly decreased numbers of granules and cytoplasmic villi. Some cells displayed degenerative or necrotic appearances. These findings correlated well with the clinical course of these cases, which improved spontaneously over time.

Adult↗
PubMed1988

Propranolol inhibits accumulation of non-esterified fatty acids in the ischemic dog heart.

The effects of propranolol and d-propranolol on the accumulation of non-esterified fatty acids (NEFA) induced by complete occlusion of the left anterior descending coronary artery (LAD) for 90 min, were investigated in dogs anesthetized with pentobarbital. The myocardial levels of eight NEFA (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic and arachidonic acids) were determined after fluorescent labelling of the NEFA with 9-anthryldiazomethane. LAD occlusion increased the myocardial levels of NEFA, especially those of arachidonic and palmitoleic acids; arachidonic acid increased by 3.5 times and palmitoleic acid by 2.9 times. Pretreatment with propranolol (1 mg/kg) inhibited almost completely the accumulation of NEFA induced by occlusion of the LAD, whereas pretreatment with d-propranolol (1 mg/kg) did not inhibit the accumulation of NEFA, although it tended to inhibit the accumulation of palmitoleic, stearic and arachidonic acids. These results suggest that the inhibitory action of propranolol on the accumulation of NEFA in the myocardium during ischemia is mainly due to its antagonistic effect at beta-adrenoceptors and probably partly due to its effect as a local anesthetic.

Animals↗
PubMed1988

In vitro and in vivo antibacterial activity of KY-109, a new orally active cephalosporin.

The in vitro and in vivo antimicrobial potencies of KY-109, a pro-drug of KY-087, were compared with those of amoxicillin, cephalexin (CEX), and cefaclor (CCL). The following results were obtained. KY-087, which is the active form of KY-109, had broad antimicrobial spectrum against Gram-positive and Gram-negative organisms, but showed low antimicrobial activity against Enterobacter sp., Serratia, and Pseudomonas sp. The antimicrobial activities of KY-087 against clinically isolated Gram-positive organisms were superior to those of CEX and CCL. The antimicrobial activities of KY-087 against Gram-negative organisms, such as Enterobacter sp., Serratia, and Pseudomonas sp., were less active. KY-087 showed dose-related bactericidal activity against Staphylococcus aureus and Escherichia coli. The therapeutic efficacy of KY-109 against experimental intraperitoneal infections caused by Gram-positive and Gram-negative organisms in mice was comparable to that of CEX but inferior to that of CCL. In experimental granuloma pouch models in rats and kidney infection in rabbits, therapeutic efficacy of KY-109 was either comparable or superior to that of CEX and CCL.

Administration, Oral↗
PubMed1987

Accumulation of nonesterified fatty acids in the dog myocardium during coronary artery occlusion determined by a method using 9-anthryldiazomethane.

The levels of nonesterified fatty acids (NEFA) in the myocardium during ischemia were determined by a simple method, which requires neither previous separation with thin-layer chromatography nor heating. After being extracted with Folch's solution, NEFA were subjected to fluorescent labeling with 9-anthryldiazomethane at room temperature, separation with high-pressure liquid chromatography, and then detection by a flow-through fluorometer. Calibration and validation studies revealed that this method was satisfactory. The left anterior descending coronary artery was completely occluded for 90 min in dogs anesthetized with pentobarbital. In the nonischemic myocardium, the levels of lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic, and arachidonic acids were 5.31, 15.85, 47.06, 2.59, 23.92, 37.90, 38.69, and 3.99 nmol/g wet tissue, respectively, and those in the ischemic myocardium 5.67, 22.16, 75.94, 6.65, 42.67, 61.75, 70.06, and 13.39 nmol/g wet tissue, respectively, the total NEFA in the former being 175.3 and that in the latter 298.3 nmol/g wet tissue. The increase in myocardial NEFA during ischemia was significant except for lauric and myristic acids, and the increase in arachidonic acid was the greatest. The ratio of the level of arachidonic acid in the ischemic myocardium to that in the nonischemic myocardium was 335.6%.

Animals↗
PubMed1987

Antiatherogenic action of eicosapentaenoic acid (EPA) in multiple oral doses.

The possible antiatherogenic action of eicosapentaenoic acid (EPA) was pharmacologically investigated using purified and ethylesterified fish oil containing 75% EPA (EPA-E) in multiple oral doses in rats and rabbits. EPA-E showed dose-dependent prevention of thrombus formation in a vascular shunt or sudden death caused by arachidonic acid injection in rats. EPA-E in daily doses ranging from 3 to 30 mg/kg slightly altered platelet aggregability and prostacyclin-like activity generated from arterial ring preparations of rats, but these alterations were not statistically significant. Further, EPA-E showed no effect on blood viscosity of rats. In cholesterol-fed rabbits, EPA-E in daily doses of 10 and 30 mg/kg moderately lowered the levels of plasma cholesterol, beta-lipoprotein, triglyceride and phospholipid, but these changes showed neither dose-dependency nor time-dependency. In this experiment, EPA-E moderately altered atherogenic plaque formation and platelet aggregability, but these alterations were not statistically significant. EPA-E showed no effect on prostacyclin-like activity generated from arterial ring preparations and blood viscosity of cholesterol-fed rabbits. It is, therefore, proposed that the antithrombotic action of EPA-E may be partially related to its effects on platelet aggregability and prostacyclin generation, but the major mechanism remains unclear.

Administration, Oral↗
PubMed1987

[Futraful and UFT, their metabolic characteristics].

Investigations were made in human on the metabolism of Futraful (FT) and UFT (combination of uracil and FT), both of which are anticancer agents of pyrimidine metabolism antagonist. As a result, it was demonstrated that from the metabolic view point, those drugs essentially have a tumor-selective toxicity. Next, the mechanism of the superior clinical anticancer effect of UFT, compared to FT, was investigated enzymatically, showing the inhibitory effect of uracil on the degradation of 5-fluorouracil generated from FT in the organs and tumor tissues. Discussions were also made for the further development of fluoropyrimidines.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Functional evaluation of tryptophanyl residues of bovine and porcine pancreatic deoxyribonucleases.

Trp-155 in bovine DNase A (EC 3.1.4.5) appeared to be unessential for the enzymatic activity for the following reasons: (1) A unique peptide which suggests the environmental difference of Trp-155 was obtained from porcine pancreatic DNase A. (2) Inactivation of the porcine DNase A by NBS modification was fairly paralleled with a decrease in the CD signal, which is characteristic of the "buried" tryptophan in the hydrophobic region (trp-191 in bovine DNase) but not of tryptophans in the hydrophilic portion. Binding of DNase to the poly I: poly C double helix confirmed the important role of this tryptophan.

Amino Acids↗
PubMed1986

[Pharmacological properties of MO-8282, a novel antidepressant].

The pharmacological properties of MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]pyridine maleate) as an antidepressant were investigated. At doses 10 times less than those of amitriptyline, MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by L-DOPA. Intermediate doses of MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized clonidine-induced suppression of exploratory activity in mice. MO-8282 moderately antagonized the ptosis but not the hypothermia induced by reserpine in mice. MO-8282 exhibited weak antagonism against the tremor, lacrimation and diarrhea induced by tremorine, but its activity was milder than that of amitriptyline. The uptake of noradrenaline into rat hypothalamic synaptosomes was inhibited by MO-8282 at concentrations 20 times less than equally effective doses of amitriptyline, but the uptake of dopamine or serotonin was unaffected by MO-8282. A single oral administration of MO-8282 at a dose of 30 mg/kg accelerated noradrenaline turnover, but did not affect dopamine and serotonin turnover in the rat brain. MO-8282 strongly inhibited noradrenaline-, histamine- or adenosine-sensitive adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of imipramine, rather resembling that of mianserin. MO-8282 did not affect monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of MO-8282 are different from those of tricyclic antidepressants and rather similar to those of mianserin, but more potent. The results, therefore, indicate that MO-8282 is possibly a novel antidepressant.

Aggression↗
PubMed1985

[UFT, UFTM, and UFTM-Dpc treatment of gastric cancer].

It became increasingly evident that UFTM chemotherapy, a combination of UFT and mitomycin C is one of the most recommendable therapy for advanced gastric cancer, especially for the treatment of Borrmann type 4 gastric cancer. Objective responses were achieved in 18 out of 26 (69.2%) patients with Borrmann type 4 gastric cancer. Moreover, UFTM-Dpc treatment, a combination therapy of UFTM plus D-penicillamine (suppressor of collagen synthesis), is proposed for the treatment of Borrmann type 4 gastric cancer from the point of view of collagen synthesis inhibition. It is likely that D-penicillamine might inhibit the peritoneal metastatic involvements, which is lethal to the patients finally.

Aged↗
PubMed1984

Factors affecting the equatorial X-ray diffraction pattern from contracting frog skeletal muscle.

Changes in the equatorial X-ray diffraction pattern from tetanized frog sartorius muscles (Rana catesbiana ) were studied by use of time-resolved data collection technique (time resolution, 0.5 sec) to give information about the dynamic properties of the cross-bridges. No significant changes in the intensity ratio of two equatorial reflections (I1,0/I1,1) were observed when isometrically contracting muscles were slowly stretched by 5-6%, in spite of marked force changes. The intensity ratio also showed no significant changes when the load on isometrically contracting muscles was suddenly increased from Po to 1.2-1.5 Po to produce isotonic muscle lengthening. Closer examination of the data indicated that a small decrease in the value of I1,1 was caused by both slow stretch and isotonic lengthening. Because of the scatter of experimental plots in I1,0, the effect of small change in I1,1 on the intensity ratio fell within the range of accuracy of measurement. It is suggested that no marked changes in myosin head orientation or in the number of the cross-bridges in the vicinity of the thin filaments take place in response to slow stretches or isotonic lengthening, and that the decreased regularity of the filament lattice may produce the change in I1,1.

Animals↗
PubMed1984

Phase-dependent polymerization and depolymerization of actin in Physarum polycephalum nuclei.

G- and F-actin contents in physarum polycephalum nuclei isolated during the progress of cell cycle were estimated and compared both by the inhibiting activity of deoxyribonuclease I (DNase I) and by the fractionation on DEAE-Toyopearl column chromatography. The inhibition of DNase appeared maximal in late S phase or early G2 phase and decreased to a minimal value in late G2 phase or M phase, while total actin content in a nucleus, which was analyzed by SDS-polyacrylamide gel electrophoresis as well as by DNase inhibition assay in the presence of 0.75 M guanidine-HCl, did not show such phase-dependent dynamics through the cell cycle.

Actins↗
PubMed1984

Mutagenicity of various Japanese foodstuffs treated with nitrite. II. Directly-acting mutagens produced from N-containing compounds in foodstuffs.

Various Japanese foodstuffs show mutagenicity after nitrite treatment at pH 4.2. Among 13 groups of foodstuffs, classified by the 'market basket' method, the group containing fish showed the highest mutagenicity in the absence of metabolic activation. Taking the daily intake of these foodstuffs into consideration, the combination of groups V (soya bean paste), VI (juice), VIII (pickles and seaweed), IX (alcoholic beverages, coffee), X (fish) and XI (meat) represents 90% of the total mutagenic activity that may be supplied by food each day. The mutagenic activities of foodstuffs in groups VII (vegetables), VII and IX were increased remarkably by nitrite treatment; the mutagenicity of alcoholic beverages was particularly affected by nitrite. The separation of wine, sake and beer into acidic, basic and neutral fractions scattered the premutagenic activities, with a large decrease in total activity. The chemical properties of the basic fraction of beer, which gave the highest mutagenicity after nitrite treatment, were examined, and two tetrahydro-beta-carboline derivatives were identified.

Chemical Phenomena↗