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Biomedical subjects

K Matsuda

Publications and source records attributed to K Matsuda.

At least 415 records · Page 23Linked to original sources

Antiallergic effect of ZCR-2060: antihistaminic action.

The antihistaminic effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060), a newly synthesized antiallergic agent, was investigated in both in vitro and in vivo studies. ZCR-2060 clearly antagonized histamine-induced contraction of isolated guinea pig ileum and trachea. In contrast, carbachol-, BaCl2- and 5-hydroxytryptamine-induced contractions of isolated guinea pig ileum were slightly inhibited by higher concentrations of ZCR-2060. 3H-Mepyramine specific binding to membranes from guinea pig lung and brain were markedly inhibited by ZCR-2060 in a concentration-dependent fashion. In the in vitro studies, the antihistaminic effect of ZCR-2060 was greater than those of cetirizine and terfenadine, but was less than that of ketotifen. In the in vivo studies, ZCR-2060 significantly inhibited the histamine-induced cutaneous reaction in rats, when administered orally 1 hr before the histamine injection. Moreover, ZCR-2060 has a long-lasting antihistaminic effect. In the in vivo studies, the antihistaminic effect of ZCR-2060 was found to be greater than that of cetirizine and terfenadine, and it was the same as that of ketotifen. Thiopental-induced sleep and spontaneous ambulatory activity in mice, however, were unaffected by ZCR-2060 at higher doses. These results indicate that ZCR-2060 has a potent, selective and long acting histamine H1-receptor antagonistic action without causing any unwanted CNS side effect.

Animals↗

Antiallergic effects of ZCR-2060: effect on allergic cutaneous reactions and rhinitis models in mice and rats.

The antiallergic action of 2-[2-[4-(diphenylmethyl)-1-piperadinyl] ethoxy] benzoic acid maleate (ZCR-2060) was investigated on allergic cutaneous reactions and nasal vascular permeability in mice and rats. ZCR-2060 markedly inhibited immediate allergic cutaneous reactions, including passive cutaneous anaphylaxis (PCA) in rats and mice; histamine-, compound 48/80- and calcium ionophore A 23187-induced cutaneous reactions in rats; and biphasic skin reactions mediated by monoclonal IgE antibody and epicutaneous challenge with antigen in mice, but did not affect 5-hydroxytryptamine-induced cutaneous reaction in rats. The antigen-induced nasal vascular permeability increase in actively and passively sensitized rats and histamine-induced nasal vascular permeability increase in rats (allergic rhinitis model) were clearly inhibited in a dose-dependent fashion by ZCR-2060. Moreover, ZCR-2060 significantly inhibited antigen-induced anaphylactic histamine release from rat peritoneal mast cells and carrageenin-induced paw edema in rats. These results suggest that ZCR-2060 has antiallergic effects on allergic cutaneous reactions and experimental rhinitis, probably due to histamine H1-receptor blockage and the inhibition of histamine release.

Animals↗

High speed polymerase chain reaction in constant flow.

A new simple reactor of the tubing type was developed for polymerase chain reaction (PCR). A thin Teflon capillary tube was used as a tubing reactor in which the reaction mixture of PCR was driven by a pump at a constant flow rate. The sample was treated with three successive thermal stages for denaturation, annealing, and elongation of DNA and primers as a function of the position in the tube. The amplification yield was about a half of that obtained by a commercial thermocycler. Moreover, the total reaction time from 12 to 18 min, which was one-tenth of the time generally required by conventional thermocyclers using metal blocks, assured substaintial amplification of a DNA fragment. In addition, this reactor could be also used for rapid cycle-sequences. This new device will be easily incorporated into automated and rapid DNA analysis systems for DNA sequencing.

Base Sequence↗

Purification and properties of bile acid sulfate sulfatase from Pseudomonas testosteroni.

The bile acid sulfate sulfatase (BSS) produced by Pseudomonas testosteroni was purified and characterized. Chromatofocusing behavior and amino acid sequence over twelve amino acid residues from N-terminus of the enzyme indicated that BSS was composed of two isoforms of which molecular weights were 125,000 and 103,000. Each isoform was a homodimer of a subunit of which molecular weight was 53,000 or 51,000, respectively. The optimum pH was 8.5 and BSS was stable at pH 5.8-8.0. The thermostability above 32 degrees C was improved by the addition of polyols, such as sorbitol, sucrose, and glycerol. BSS was a Mn(2+)-dependent enzyme and contained 1-2 atoms of manganese in its own protein molecule. All 3 alpha-sulfate esters of the bile acids routinely appearing in human serum were hydrolyzed by BSS to 3 beta-hydroxyl iso-compounds corresponding to each bile acid and sulfuric acid. We tentatively named this novel enzyme BSS (bile acid 3 alpha-sulfate sulfohydrolase).

Amino Acid Sequence↗

Insulin sensitivity and glycemic control before and after parathyroidectomy in a diabetic patient with familial multiple endocrine neoplasia type 1.

We treated a diabetic patient with familial multiple endocrine neoplasia type 1 (MEN 1) who had undergone total pancreatoduodenectomy. The patient received insulin and showed signs of symptomatic primary hyperparathyroidism (PHPT). The insulin requirement to control blood glucose before and after parathyroidectomy was compared by using an artificial pancreas. The insulin infusion rate during the day and at night was reduced to about one-third and half, respectively, after parathyroidectomy with autotransplantation of parathyroid tissues into the forearm. The daily insulin dose was reduced from 36 units to 14 units 2 weeks after surgery, and glycemic control showed further improvement 2 months after surgery with the same dose of insulin for up to 6 months. These observations suggest that insulin sensitivity increases after surgical correction of PHPT.

Adult↗

A new skin equivalent: keratinocytes proliferated and differentiated on collagen sponge containing fibroblasts.

Three types of artificial skin containing keratinocytic components were prepared and tested for comparison. Keratinocytes were cultured on the artificial skin dermis (collagen sponge) by the air-liquid interface culture method. In order to create continuous keratinocytic layers on the artificial skin dermis, pores of its uppermost layer were filled beforehand with type I collagen gel, Matrigel, or fibroblasts. A band of keratinocytes consisting of two to six cell layers was formed on collagen gel-coated artificial skin dermis. On Matrigel-coated artificial skin dermis, keratinocytes were piled up into about 20 cell layers, but cell differentiation was incomplete; cornified material was not fully developed, and the proportion of cuboidal cells was very high compared with normal epidermis. Keratinocytes formed continuous layers on the fibroblasts-artificial skin dermis complex without gel coating. Keratinocytes proliferated well and differentiated properly on this matrix, and their histologic appearance was similar to that of normal epidermis. Thus keratinocytes cultured on the fibroblast-artificial skin dermis complex seem to be a good skin equivalent.

Adult↗

Effects of an angiotensin II receptor antagonist, TCV-116, on insulin sensitivity in fructose-fed rats.

This study was designed to examine the effects of an angiotensin II receptor antagonist on insulin sensitivity in an insulin-resistant hypertensive rat model (fructose-fed rats; FFR). Male Sprague-Dawley rats were fed a fructose-rich diet or standard chow for 4 weeks and then treated with either 1 mg/kg/day of TCV-116 (angiotensin II receptor antagonist) or vehicle for a further 2 weeks. Steady-state plasma glucose (SSPG) was measured while the animals were conscious. Insulin (2.5 mU/kg/min) and glucose (8 mg/kg/min) were simultaneously infused to determine insulin sensitivity in each group. The mean arterial pressure (MAP) was higher in the FFR (133 +/- 5 mmHg) than in the control group (120 +/- 3), and TCV-116 (110 +/- 4) decreased MAP significantly. SSPG was also higher in the FFR group (207 +/- 6 mg/dl) than in the control (137 +/- 10, p < 0.01), and TCV-116 (171 +/- 7) significantly reduced SSPG. The FFR group also had higher steady-state plasma insulin (SSPI) levels than the control (107 +/- 10 microU/ml for FFR and 63 +/- 12 for control, p < 0.05), and TCV-116 attenuated the increase in SSPI (73 +/- 11, p < 0.05). Thus, the angiotensin II receptor antagonist improved insulin resistance, as assessed by determining SSPG in FFR, suggesting that angiotensin II antagonism may play an important role in improving of insulin resistance in FFR.

Angiotensin Receptor Antagonists↗

EGF stimulates both cyclooxygenase activity and cell proliferation of cultured guinea pig gastric mucous cells.

Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and insulin all dose-dependently stimulated [3H]-thymidine incorporation into guinea pig gastric mucous cells cultured in vitro. On the other hand, other growth factors, e.g., platelet-derived growth factor (PDGF) and gastrointestinal hormones, such as gastrin, had no effect on DNA synthesis in these cells. Exposure of the cells to EGF at concentrations which stimulated DNA synthesis caused increases in both prostaglandin (PG) E2 release and cyclooxygenase (COX) enzyme protein synthesis, as evaluated by Western blot analysis. These results suggest that such increases in DNA synthesis and PGE2 release may be involved, at least in part, in the mechanism of EGF-induced local regulation of gastric mucosal integrity.

Animals↗

The Gordon Wilson Lecture. Regulation of thromboxane A2 receptors by testosterone: implications for steroid abuse and cardiovascular disease.

Thromboxane A2 (TXA2), a platelet aggregator and vasoconstrictor, has been implicated as a potential pathophysiologic mediator of a wide variety of cardiovascular diseases. It is well established that men are at greater risk for cardiovascular disease compared to premenopausal females. Abuse of androgenic/anabolic steroids has been associated with thrombotic cardiovascular diseases in young male athletes. These observations along with several others have led to the hypothesis that testosterone may regulate the expression of TXA2 receptors. Rat aortic smooth muscle cells (RASMC) and human erythroleukemia cells (HEL), a megakaryocyte-like cell, were incubated with testosterone. TXA2 receptor affinity (Kd) and density (Bmax) were determined via equilibrium binding experiments using the radiolabeled TXA2 mimetic [125I]-BOP. Testosterone significantly increased the Bmax without any significant change in Kd. Hydroxyflutamide (1 microM), an androgen receptor antagonist, completely blocked the effect of testosterone. Dihydrotestosterone, the active metabolite of testosterone also increased Bmax in a concentration-dependent manner and was more potent than testosterone. These observations along with several others are consistent with the notion that androgenic steroids may regulate the expression of functional TXA2 receptors in HEL and RASMC. These results raise the possibility that the increase in TXA2 receptor density induced by testosterone may contribute to its thrombotic potential in cardiovascular diseases.

Animals↗

[Surgery of type A acute aortic dissection with gelatin-resorcin-formal (GRF) biological glue--study of six cases].

GFR (Gelatin-Resorcin-Formalin) glue consists of mixture of gelatin and resorcin. The mixture is hardened by the addition of medical form-aldehyde, creating tridimensional network. From August 1991 to February 1993, six patients of type A acute aortic dissection underwent repair of false lumen with GRF glue. Including one female, the mean age was 57.3 years old ranged 51 years old to 64 years old. The entry of aortic intima were found in the ascending aorta in 4 cases, in the greater curvature of aortic arch in one case, and in the lesser curvature of aortic arch in one case. We used GRF glue for adhesion of intimal and medial wall of dissecting aneurysm in all cases. In case 1, the ascending aorta was replaced with a ringed intraluminal graft, and in case 2, the ascending aorta was replaced with a graft. In case 3 and 4, the aortic wall was closed primarily using GRF glue after patch closure of an entry. In case 5 and 6, the ascending aorta including an aortic arch was replaced with a graft. We revealed that GRF glue could harden the thin wall of aorta in the acute phase.

Aortic Dissection↗

[Studies on aspoxicillin for its transfer to the skin].

To evaluate the usefulness of aspoxicillin (ASPC) in the field of plastic and reconstructive surgery, we examined its transfer to the skin. 1. After intravenous drip infusion of ASPC for 1 hour at a dose of 2 g in 13 adults and at 1 g in 2 children, the mean serum ASPC concentration 1 hour after termination of the infusion was 70.46 +/- 28.05 micrograms/ml. The mean concentration in the skin tissue 1 hour after infusion in 15 patients was 32.45 +/- 18.47 micrograms/g. The rate of transfer to the skin 1 hour after infusion in the 15 patients was 52.9 +/- 29.7%. 2. The ASPC concentrations in skin tissues and the rates of its transfer to the skin did not differ significantly between 5 patients with facial surgery and 10 with surgery in the trunk or limbs. 3. To prevent postoperative infections, ASPC was intravenously drip infused twice daily for 2 approximately 3 days after operation at a dose of 2 g in adults and 1 g in children. No postoperative infection occurred in any patient, suggesting the effectiveness of this drug. In addition, no side effects or abnormalities in clinical examination values were observed.

Adolescent↗

[A 78-year-old man with progressive gait disturbance, dysphagia, and dementia].

We report a 78-year-old man with progressive gait disturbance, dementia, and dysphagia. He was apparently well until 75 years of age in 1989 when he had an insidious onset of gait disturbance. In October of 1991, he was treated with levodopa and amantadine HCl in another hospital, but he developed visual hallucination right after these medications, and the drugs were discontinued. He also developed difficulty in swallowing with frequent aspiration pneumonia. He was admitted to our hospital on January 13, 1992. On admission, the patient was chronically ill Japanese man; his blood pressure was 118/70 mmHg, body temperature 35.4 degrees C, and heart rate 72 and regular. No anemia or jaundice was noted; lungs were clear and no heart murmur was audible. The abdomen was flat but rigid to palpation without tenderness; no organomegaly was noted. On neurologic examination, he was alert but disoriented to all spheres; he was apparently demented and the score of the mini-mental test was 11. He did not appear to have aphasia or apraxia. Cranial nerves appeared intact, but he had a mask-like face and a slight limitation in the upward gaze; his voice was small. He was unable to stand or walk; he showed marked akinesia and moderate rigidity in his neck and the trunk. Deep reflexes were generally elicited normally or slightly weakly. Plantar response was extensor on the left and flexor on the right. No grasp reflex was present. Sensory examination showed questionable loss of touch in the glove- and -stocking distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Superiority of plasma 11-dehydro-TXB2 to TXB2 as an index of in vivo TX formation in rabbits after dosing of CS-518, a TX synthase inhibitor.

We compared plasma 11-dhTXB2 and TXB2 for their ability to reflect in vivo TX formation in rabbits treated with AA and CS-518, a TX synthase inhibitor. The average plasma level of TXB2 in rabbits was much higher than that of 11-dhTXB2, probably because of artificial formation of TXB2 during blood sampling. CS-518 (1 mg/kg, p.o.) caused a long-lasting suppression of the 11-dhTXB2 level, and its inhibitory effect on 11-dhTXB2 was much more extensive than that on TXB2. AA-infusion for 5 min resulted in transient and remarkable increases of both TXs, and prevention of such increases by CS-518 pretreatment (1 mg/kg, i.v.) was shown: inhibitions of 11-dhTXB2 and TXB2 were 85% and 40%, respectively. The inhibitory effect caused by CS-518, which was more clearly observed on plasma 11-dhTXB2 than on TXB2, was due to not only the completely inhibited levels without artificial formation but also the durable high levels based on the long half-life of 11-dhTXB2 in AA-infused rabbits. CS-518 injection during sustained AA-infusion also resulted in a 2-fold faster disappearance of plasma 11-dhTXB2 than was seen without CS-518, despite its long half-life. Considering the absence of artificial formation, the long half-life, and the good response to change of TX formation, plasma 11-dhTXB2 is superior to TXB2 as an index for monitoring in vivo TX synthase activity and its pharmacological modification with AA and CS-518.

Animals↗

Alteration of eicosanoid production in the sensitized guinea pig lung by CS-518.

The effects of CS-518 (sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo [b]thiophene-6-carboxylate), a thromboxane A2 synthase inhibitor, on changes in arachidonic acid metabolism were investigated in the lung of actively sensitized guinea pigs. Antigen challenge enhanced the production of thromboxane A2 as well as histamine and peptide leukotrienes in lung fragments. Exogenous leukotriene D4 also stimulated significant thromboxane A2 production in the non-sensitized lung in vitro. CS-518 was effective in preventing the thromboxane A2 production induced by either antigen or leukotriene D4, and the IC50 values were 90 and 7.5 ng/ml (320 and 27 nM), respectively. CS-518 markedly potentiated the production of prostaglandin E2 and I2 with slight inhibition of leukotriene formation, but indomethacin significantly stimulated leukotriene production. When CS-518 was administered orally, it induced long-lasting inhibition of thromboxane A2 production and potentiation of prostaglandin I2 production in guinea pig lung. Thus, CS-518 not only inhibited thromboxane production but also improved the change in arachidonic acid metabolism in the guinea pig bronchoalveolar tissue during allergic reaction in vivo as well as in vitro, which suggests amelioration of the asthmatic condition.

Administration, Oral↗