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Biomedical subjects

K Ishihara

Publications and source records attributed to K Ishihara.

At least 379 records · Page 21Linked to original sources

Effects of acid-inhibitory antiulcer drugs on mucin biosynthesis in the rat stomach.

The effects of the anti-acid secretory agents, cimetidine (N-cyano-N'-methyl-N"-(2-([(5-methyl-1H-imidazol-4-yl)methyl]thio)ethyl) guanidine), ranitidine (N-(2-(((-5-[(dimethylamino)methyl]-2-furanyl)methyl)thio)ethyl)-N'-meth yl- 2-nitro-1,1-ethene-diamine), roxatidine (2-acetoxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl) acetamide hydrochloride), FRG-8813 (2-(furfurylsulfinyl)-N-(4-[4-(piperidinomethyl)-2-pyridyl]o xy-(z)-2- butenyl)acetamide), omeprazole (5-methoxy-2-([(4-methoxy-3,5-dimethylpyridinyl)methyl]sulfinyl)- 1H-benzimidazole), and NC-1300-O-3 (2-([2-(isobutylmethylamino)benzyl]sulfinyl)-1H- benzimidazole), on mucin biosynthesis were studied in rat gastric mucosa by using an organ culture technique. [3H]Glucosamine incorporation was stimulated in the corpus region by the histamine H2 receptor antagonists which have a six-membered aromatic ring, roxatidine and FRG-8813, and the new H+,K(+)-ATPase inhibitor, NC-1300-O-3. Thus, these drugs not only inhibit acid secretion but may also promote gastric mucosal protective actions. The present observations also demonstrate that the determination of mucin biosynthesis may be a useful tool for evaluation of mucosal protective activity.

Animals↗

Hemocompatibility on graft copolymers composed of poly(2-methacryloyloxyethyl phosphorylcholine) side chain and poly(n-butyl methacrylate) backbone.

To improve the hemocompatibility on hydrophobic biomedical materials by a simple coating technique, graft copolymers composed of a hydrophilic side chain with phospholipid polar groups and a hydrophobic backbone were synthesized. The hydrophilic chain had phospholipid polar groups, poly[2-methacryloyloxyethyl phosphorylcholine (MPC)], and the hydrophobic backbone was poly[n-butyl methacrylate (BMA)]. Because the graft copolymers obtained could dissolve in ethanol, they could be used as a coating material. When the poly(MPC-graft-BMA) was coated onto a poly(BMA) membrane, the composition of the MPC units on the surface was maintained in the bulk graft copolymer even after immersion in water. Protein adsorption on the membrane coated with the graft copolymer from human plasma detected by a gold-colloid labeled immunoassay was drastically decreased compared with that on glass and the original membrane. Moreover, blood cell adhesion, activation, and aggregation on the membrane after contact with human citrated whole blood were suppressed by the coating of the graft copolymer. These results clearly show that the poly(MPC-graft-BMA) is a suitable material for improving hemocompatibility on the biomedical devices because of its protein adsorption and cell adhesion resistant properties.

Adsorption↗

Selective adhesion of platelets on a polyion complex composed of phospholipid polymers containing sulfonate groups and quarternary ammonium groups.

We investigated the effects of electrical charges on cell-polymer interactions of poly[2-methacryloyloxyethyl phosphorylcholine(MPC)-co-n-butyl methacrylate (BMA)] (PMB) having excellent blood compatibility, by copolymerizing anionic or cationic methacrylates with MPC and BMA. A polyion complex (PIC) composed of anionic and cationic MPC copolymers was also prepared. When the cell adhesion on these polymer surfaces from rabbit whole blood was evaluated, we observed a considerable reduction in cell adhesion on the MPC copolymers compared with that on poly(BMA), even when the MPC copolymer was electrically charged. On the other hand, many platelets selectively adhered to the PIC surface from whole blood, but the adherent platelets maintained a discoid shape. The amount of adenosine triphosphate (ATP) in platelets adherent on the PMB or the PIC from a platelet-rich plasma (PRP) was more than 75% of that in the original PRP, which indicated that the activity of these platelets remained high. However, in the platelets adherent to poly(BMA), only a small amount of ATP remained. Protein adsorption on the polymer surface from human plasma was investigated using a gold-colloid-labeled immunoassay against albumin gamma-globulin, and fibrinogen. Many of these proteins adsorbed on poly(BMA), whereas a small amount of protein was observed on the MPC copolymers that had an electrical charge. Albumin adsorption and suppression of gamma-globulin and fibrinogen adsorption were found on the PIC. Therefore, the introduction of electrical charges in the PMB did not have an adverse effect on cell adhesion and protein adsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Formation of the adult rudiment of sea urchins is influenced by thyroid hormones.

After the sea urchin embryo has developed to a pluteus larva, the adult rudiment (sea urchin rudiment) is formed, with other adult structures, on the left side of the larva and finally the juvenile sea urchin is formed after metamorphosis. We report here that thyroid hormones (THs) are involved in the formation of the adult rudiment and the adult-type skeleton and the resorption of larval tissues of the sea urchin. The contents of THs in the larval body were determined by radioimmunoassay after the separation of individual THs by HPLC. We confirmed the presence of THs in the larval body and in algae on which the larvae feed. The THs accumulate gradually following the development of the larva and reach maximum levels at the eight-armed stage when the adult rudiment is completed. These results suggest that the development of the larva is influenced by THs accumulated in the larval body. However, inhibitors for the synthesis of THs do not affect the development of the larval body, suggesting a supply of THs from algae.

Animals↗

Gating mechanism of the cloned inward rectifier potassium channel from mouse heart.

The complementary DNA encoding the inward rectifier potassium channel was cloned from the adult mouse heart by using the polymerase chain reaction. The clone had the nucleotide sequence identical to that of the IRK1 gene cloned from a mouse macrophage cell line. Northern blot analysis revealed that the transcript of this gene was mainly expressed in the ventricle, where the inward rectifier K+ channel plays a predominant role in maintaining the high negative value of the resting membrane potential. The current expressed by injection of the complementary RNA of the cloned gene into Xenopus oocytes showed a marked inward rectification that depends on the driving force of K+. A region of negative slope conductance was observed in the current-voltage relationship at potentials positive to the reversal potential. When the extracellular K+ concentration was raised, the increase in outward current amplitude resulted in the "crossover" of outward current-voltage relations. The fast time-dependent increase in current amplitude was recorded upon membrane repolarization from a potential positive to the reversal potential. The kinetics of the time-dependent current was very similar to that of the intrinsic gating mechanism of the native cardiac inward rectifier K+ channel. Our results suggest the existence of the intrinsic gating mechanism, accounting for the extent of rectification in the current-voltage relationship in the expressed channel.

Action Potentials↗

Production of docosahexaenoic acid by marine bacteria isolated from deep sea fish.

Five bacterial strains isolated from the intestine of deep sea fish were shown to produce docosahexaenoic acid (22:6n-3; DHA) at a level of 6.4 to 11.6% of total fatty acids when incubated in DHA-free medium. In all of the strains examined, other polyunsaturated fatty acids were barely detectable, except for eicosapentaenoic acid (20:5n-3). A typical strain, such as T3615, produced DHA at a concentration of about 0.8 mg/L within six days of aerobic incubation at 5 degrees C and under atmospheric pressure. The T3615 strain, belonging to the genus Vibrio, is rod-shaped, Gram-negative, motile and facultatively anaerobic.

Animals↗

Effects of the new histamine H2 receptor antagonist, FRG-8813, on gastric mucin in rats with or without acidified ethanol-induced gastric damage.

It is not presently well understood whether the histamine H2 receptor antagonist has a function other than the inhibition of gastric acid secretion, such as the effect on the gastric mucosal defence mechanism. In this paper, we report the effect of FRG-8813 (N-[4-[4-(piperidinylmethyl)pyridyl-2-oxy]-(Z)-2-butenyl]-2- (furfurylsulfinyl) acetamide), a new histamine H2 receptor antagonist, on the rat gastric mucin content with or without 0.15N HCl-ethanol (60 %)-induced gastric damage. The prior administration of FRG-8813 significantly inhibited the occurrence of macroscopically observable hemorrhagic lesions induced by the acidified ethanol treatment. Using a newly developed biochemical method, the mucin content of the deep corpus and antral mucosa of the acidified ethanol-treated animals was significantly reduced to 50% and 32% of the control, respectively. These reductions were inhibited by the pretreatment with FRG-8813. Total mucin content in the entire stomach recovered to about 80% of the control value after pretreatment with FRG-8813. A single oral administration of FRG-8813 (30 mg/kg) caused no significant change in the total mucin content, but mucin in the adherent mucus gel layer selectively and significantly increased to 250% of the control. These results suggest that FRG-8813 not only inhibits acid secretion but may also affect the gastric mucosal defensive mechanism as well.

Acetamides↗

LTP of mossy fiber-stimulated potentials in CA3 during learning in rats.

The study was done to determine whether long-term potentiation (LTP) of the potentials occurs at mossy fiber (MF)-CA3 synapses with the advance of learning in unrestrained and unanesthetized rats. The rats were divided into two groups, the test and control groups. The test group was given daily learning tasks in the radial arm maze, whereas the control group was similarly handled without learning tasks. Complete acquisition of learning was observed in the test group on day 5, and the learning was maintained over 3 days. Under freely moving conditions, a significant increase in population spikes (PS) elicited by MF stimulation with the progress in learning was observed in the test group, and the PS potentiation remained stable after day 4. Furthermore, on day 7, when MF stimulation-induced PS in the test group were compared with that in the control group in pentobarbital-anesthetized rats, the responses were comparatively higher in the former. As the training-induced PS potentiation in CA3 occurred with the advance of learning, these findings suggest that LTP in CA3 induced by learning may be related to memory storage.

Animals↗

Improvement of hemocompatibility on a cellulose dialysis membrane with a novel biomedical polymer having a phospholipid polar group.

To improve surface hemocompatibility on cellulose hollow fibers for hemodialysis, newly designed hemocompatible polymers with a phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers, were introduced on the surface through two different methods: direct grafting of MPC on the surface, or coating of a water-soluble cellulose grafted with MPC. The MPC was polymerized using cerium ion as an initiator in the cellulose hollow fibers, and the poly(MPC) chains were grafted directly on the surface. Another modification of the cellulose hollow fibers was attempted by coating them with a water-soluble graft copolymer composed of a poly(MPC) side chain and a cellulose backbone. The coating process from an aqueous solution of the graft copolymer was very convenient, and the graft copolymer on the surface was not detached even after water circulated into the hollow fibers. These cellulose hollow fibers modified with MPC polymers displayed excellent hemocompatibility such as prevention of blood cell adhesion and aggregation after contact with blood without an anticoagulant. The permeability of the hollow fibers did not decrease as a result of these modifications. From these results, it is clearly suggested that introduction of the MPC units was effective for improving the hemocompatibility of the hollow fibers for hemodialysis.

Animals↗

Role of microtubules in contractile dysfunction of hypertrophied cardiocytes.

Cardiac hypertrophy in response to systolic pressure overloading frequently results in contractile dysfunction, the cause for which has been unknown. Since, in contrast, the same degree and duration of hypertrophy in response to systolic volume overloading does not result in contractile dysfunction, we postulated that the contractile dysfunction of pressure hypertrophied myocardium might result from a direct effect of stress as opposed to strain loading on an intracellular structure of the hypertrophied cardiocyte. The specific hypothesis tested here is that the microtubule component of the cytoskeleton is such an intracellular structure, which, forming in excess, impedes sarcomere motion. The feline right ventricle was either pressure overloaded by pulmonary artery banding or volume overloaded by atrial septotomy. The quantity of microtubules was estimated from immunoblots and immunofluorescent micrographs, and their mechanical effects were assessed by measuring sarcomere motion during microtubule depolymerization. We show here that stress loading increases the microtubule component of the cardiac muscle cell cytoskeleton; this apparently is responsible for the entirety of the cellular contractile dysfunction seen in our model of pressure-hypertrophied myocardium. No such effects were seen in right ventricular cardiocytes from normal or volume-overloaded cats or in left ventricular cardiocytes from any group of cats. Importantly, the linked microtubule and contractile abnormalities are persistent and thus may be found to have significance for the deterioration of initially compensatory cardiac hypertrophy into the congestive heart failure state.

Animals↗

Effect of methylene chain length in phospholipid moiety on blood compatibility of phospholipid polymers.

To investigate the effects of the methylene chain length between the phospholipid polar group and the backbone on blood compatibility of a phospholipid polymer, copolymers of omega-methacryloyloxyalkyl phosphorylcholine (MAPC) with n-butyl methacrylate (BMA) were synthesized. The methylene chains were ethylene (n = 2), tetramethylene (n = 4), and hexamethylene (n = 6). Every MAPC copolymer with an MAPC mole fraction in the range of 0.1-0.3 was soluble in ethanol but only swelled in water, and the equilibrium water fraction of the water-swollen MAPC copolymer membrane decreased with the length of the methylene chain. When a rabbit platelet-rich plasma was applied on the MAPC copolymer surface with an 0.1 MAPC mol fraction for 180 min, the number of adhered platelets depended on the length of the methylene chain in the MAPC moiety of the copolymer. The amount of phospholipid adsorbed on the MAPC copolymer from human plasma was larger than that on hydrophobic poly(BMA) and increased with the length of the methylene chain in the MAPC moiety. That is, the reduction of platelet adhesion corresponded to the increase in the amount of phospholipid adsorbed on the MAPC copolymer.

Adsorption↗

Effects of chronic beta-adrenergic blockade on the left ventricular and cardiocyte abnormalities of chronic canine mitral regurgitation.

The mechanism by which beta blockade improves left ventricular dysfunction in various cardiomyopathies has been ascribed to improved contractile function of the myocardium or to improved beta-adrenergic responsiveness. In this study we tested two hypotheses: (a) that chronic beta blockade would improve the left ventricular dysfunction which develops in mitral regurgitation, and (b) that an important mechanism of this effect would be improved innate contractile function of the myocardium. Two groups of six dogs with chronic severe mitral regurgitation were studied. After 3 mo both groups had developed similar and significant left ventricular dysfunction. One group was then gradually beta-blocked while the second group continued to be observed without further intervention. In the group that remained unblocked, contractile function remained depressed. However, in the group that received chronic beta blockade, contractile function improved substantially. The contractility of cardiocytes isolated from the unblocked hearts and then studied in the absence of beta receptor stimulation was extremely depressed. However, contractility of cardiocytes isolated from the beta-blocked ventricles was virtually normal. Consistent with these data, myofibrillar density was much higher, 55 +/- 4% in the beta-blocked group vs. 39 +/- 2% (P < 0.01) in the unblocked group; thus, there were more contractile elements to generate force in the beta-blocked group. We conclude that chronic beta blockade improves left ventricular function in chronic experimental mitral regurgitation. This improvement was associated with an improvement in the innate contractile function of isolated cardiocytes, which in turn is associated with an increase in the number of contractile elements.

Adrenergic beta-Antagonists↗

Effects of Z-300, a new histamine H2-receptor antagonist, on mucin biosynthesis in rat gastric mucosa.

We examined the effects of Z-300 (N-[3-[3- (piperidinomethyl)phenoxy]propyl]-2-(2-hydroxy-ethyl-1-thio)acetam ido.2- (4-hydroxy benzoyl)benzoate), a newly-synthesized selective histamine H2-receptor antagonist, on mucin in rat gastric mucosa. Deep corpus mucin content increased significantly to 127% of the control after the administration of 30 mg/kg of Z-300, whereas that in the antral mucosa did not increase. The addition of Z-300 significantly increased [3H]-labeled mucin in the corpus region. In the antrum, biosynthetic activity showed no significant change by 10(-8)-10(-5) M of Z-300. These results suggest that Z-300 not only inhibits acid secretion but may also promote gastric mucus metabolism in the corpus region.

Acetamides↗

Differences in protein structure and similarities in catalytic function of two L-stereoselective carbonyl reductases from bakers' yeast.

We purified and studied two L-stereoselective carbonyl reductases from bakers' yeast (Saccharomyces cerevisiae). One catalyzed exclusively the enantioselective reduction of carbonyl compounds such as beta-keto esters and the other acted on alpha-acetoxy ketones and beta-keto esters. The enzymes had identical molecular weights and catalyzed the L-stereoselective reduction of various carbonyl compounds with similar substrate specificity, but they were different proteins coded by different genes.

Alcohol Oxidoreductases↗

T cell abnormalities in mixed connective tissue disease complicated with Klinefelter's syndrome.

We report a 28-year-old Japanese with Klinefelter's syndrome who developed mixed connective disease (MCTD) and Sjögren syndrome. Previously being well, he presented with Raynaud's phenomenon, dry eye, fever and polyarthralgia. Clinical examinations revealed anti-nRNP autoantibody, leukopenia and lung fibrosis. Then he was found to have Klinefelter's syndrome. Flow cytometric analysis showed a relative increase of peripheral CD8+ T lymphocytes carrying either HLA-DR or CD57. Lymphocyte IL-2 production induced in vitro by concanavalin A was decreased. Such T cell abnormalities may be implicated in the development of autoimmune disease in Klinefelter's syndrome.

Adult↗

[Treatment modalities and hypothalamo-pituitary-adrenal (HPA) axis suppression in Japanese patients with asthma].

We examined HPA axis function using a short tetracosactrin test in 94 asthmatics treated with three different modalities. The first group, (B + S), consisted of 41 patients taking BDP (910 +/- 320 micrograms, daily) plus a short term burst of oral steroids (20-40 mg daily, 3-7 days/course, 1-18 courses/year). The second group, (B + R), consisted of 19 patients taking BDP (1076 +/- 410 micrograms, daily) plus continuous oral steroids (2.5-20 mg/day for 1.8-24 years). The third group, (B alone), consisted of 34 patients taking BDP only (615 +/- 258 micrograms, daily). All patients had been inhaling BDP for more than 1 year. The rise in cortisol in response to tetracosactrin in B + S, B + R, and B alone was 12 +/- 4.3 micrograms/dl, 7.0 +/- 5.0 micrograms/dl and 14 +/- 4.5 micrograms/dl, respectively, and achieved cortisol was 21 +/- 4.5 micrograms/dl, 12 +/- 7.2 micrograms/dl and 23 +/- 4.2 micrograms/dl;, respectively. Both values were significantly lower in the B + R group than in either B + S or B alone. However, there was no difference between B + S and B alone, although the BDP dose was significantly larger in the B + S group. Significant HPA axis suppression (rise in cortisol < 7 micrograms/dl and achieved cortisol < 18 micrograms/dl) was seen in 7 patients. Although HPA axis suppression was more frequently seen in B + R (10/19), no significant difference was seen between B + S and B alone (4/41 and 1/34, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

[A case of mediastinal parathyroid adenoma diagnosed by transtracheal needle aspiration].

Chest radiography of a 73-year-old man with upper abdominal pain showed hypercalcemia and an upper mediastinal mass. Functional mediastinal parathyroid adenoma was diagnosed, because of abnormally high levels of PTH in his serum and in fluid collected by transtracheal needle aspiration from the mediastinal mass. We resected the adenoma operatively. It a cystic tumor located behind the superior vena cava and the trachea. The inferior end of the tumor was as low as the aortic arch, and superiorly the tumor was attached to the inferior pole of the thyroid gland by a vascular pedicle. Histologically adenoma cells were predominant. This tumor was a mediastinal parathyroid adenoma by location, but because it was attached to the thyroid gland superiorly, it may have originated from the superior parathyroid gland and then descended because of its weight into the posterior superior mediastinum. Thus, it cannot be considered an ectopic parathyroid adenoma in origin. Mediastinal parathyroid adenoma is a rare disease, and these tumors are usually so small that correct localization of the adenoma is often difficult even by CT scan or scintigram. This is the first reported case of a mediastinal parathyroid adenoma that appeared as a mediastinal mass on a plain chest radiography and in which the level of PTH in the fluid collected from the mass by transtracheal needle aspiration was high.

Adenoma↗