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Biomedical subjects

Y Nagamatsu

Publications and source records attributed to Y Nagamatsu.

At least 19 recordsLinked to original sources
PubMed1992

Antithrombotic effect of ticlopidine on He-Ne laser-induced thrombus formation in rat mesenteric microvessels.

The inhibitory effects of ticlopidine and acetylsalicylic acid (ASA) on thrombus formation in rat mesenteric microvessels were studied. The results were compared with the effect of the drugs on platelet aggregation in citrated whole blood. He-Ne laser-induced thrombus formation in arterioles and in venules was significantly inhibited by 100 mg/kg ticlopidine. In contrast, a higher dose of ASA (300 mg/kg) was needed to inhibit thrombus formation and the effects of ASA were observed only in arterioles and not in venules. In addition, although the inhibition by ASA in arterioles was not strong it followed a dose-dependent manner, suggesting that the differential effect of ASA on platelets and endothelium may not be evident in vivo. Ticlopidine and ASA strongly inhibited ADP-induced whole blood platelet aggregation, but not collagen- or thrombin-induced platelet aggregation.

Animals↗
PubMed1992

Application of poly-L-lysine to purification of leukocyte cathepsin G by affinity chromatography.

Poly-L-lysine with molecular masses of 3.3-290 kDa increased the amidolytic activities of leukocyte elastase and cathepsin G at low concentration, but had little effect on the activities of pancreatic elastase, alpha-chymotrypsin, plasmin and thrombin. Highly purified cathepsin G was obtained from column of EAH Sepharose 4B or Suc-L-Tyr-D-Leu-D-Val-pNA-Sepharose (affinity chromatography) by elution with poly-L-lysine solution (0.4 mg/ml, molecular weight (MW.) 290000 or 2.2 mg/ml, MW. 3300). Leukocyte elastase, adsorbed to Suc-L-Tyr-D-Leu-D-Val-pNA-Sepharose, was not eluted with poly-L-lysine solution. The amino acid composition of purified cathepsin G has been determined.

Amino Acid Sequence↗
PubMed1992

Bioavailability study of commercial sustained-release preparations of diclofenac sodium in gastrointestinal physiology regulated-dogs.

The gastrointestinal (GI) physiology of beagle dogs was regulated with a combined-treatment of intramuscular pentagastrin (10 micrograms/kg x 2) and intravenous atropine sulfate (0.02 mg/kg x 1). Here, the gastric acidity, the gastric emptying time and the small intestinal transit time in the regulated-dogs were respectively around pH 2, 0.7h and 4h, approximating those in healthy humans. The superiority of the regulated-dogs over the intact dogs was confirmed in comparative bioavailability studies by using two classes of commercial preparations. Both the conventional tablet and the sustained-release capsule of diclofenac sodium exhibited simple and similar average plasma concentration-time curves of free diclofenac in the intact dogs, while the latter preparation is reported to reveal a bimodal plasma curve of the drug in healthy humans. The regulated-dogs, however, permitted a bimodal average plasma pattern of the drug for the capsules due to an approximation of the GI physiology between humans and these classes of the dogs. The combined-treatment of beagle dogs with pentagastrin and atropine sulfate seems to supply a useful animal model in predicting the absorption characteristics of the sustained-release preparations and poor water-soluble drugs.

Animals↗
PubMed1991

Determination of leukocyte elastase concentration in plasma and serum by a simple method using a specific synthetic substrate.

The concentration of leukocyte elastase (ELP) in plasma and serum was determined by an amidolysis method using a specific synthetic substrate for ELP, Suc-Ala-Tyr-Leu-Val-pNA. Results were compared with those using ELISA. ELP levels in plasma from healthy donors were similar to those determined by ELISA; however, the levels in serum were lower than those determined by ELISA. Correlation coefficients of ELP levels in plasma and serum as measured by the two methods were 0.75 (amidolysis) and 0.90 (ELISA). On the other hand, the correlation coefficient between serum ELP by the two methods was 0.83. Half of the ELP levels in plasma from 150 patients and serum from 400 patients were significantly elevated when compared with those from healthy donors, and the ELP elevation determined by amidolytic assay correlated with some variables in blood, namely fibrin(ogen)-degraded products, fibrinogen, GOT, GPT, gamma-GTP, LDH and leucine aminopeptidase. Despite the fact that the amidolysis method detects the alpha 2-macroglobulin-ELP complex while ELISA detects the alpha 1-antitrypsin-ELP complex, a comparative study showed amidolysis to provide sufficiently sensitive measurement of both plasma and serum ELP.

Adult↗
PubMed1991

Amino acids and peptides. XXX. Synthesis of eglin c (41-49) and eglin c (60-63) and examination of their inhibitory activity towards human leukocyte elastase, cathepsin G, porcine pancreatic elastase and alpha-chymotrypsin.

H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OH and H-Thr-Asn-Val-Val-OH, which correspond to the sequences 41-49 and 60-63 of eglin c, respectively, were synthesized by a conventional solution approach using the newly developed 6-chloro-2-pyridyl ester method. The inhibitory activities of the above two peptides against human leukocyte elastase, cathepsin G, porcine pancreatic elastase and alpha-chymotrypsin were examined in comparison with those of the corresponding methyl esters.

Amino Acid Sequence↗
PubMed1990

Synthesis of a trihexacontapeptide corresponding to the sequence 8-70 of eglin c and studies on the relationship between the structure and the inhibitory activity against human leukocyte elastase, cathepsin G and alpha-chymotrypsin.

A trihexacontapeptide corresponding to the sequence 8-70 of eglin c and its related peptides were synthesized by the conventional solution method and their inhibitory activity against human leukocyte elastase, cathepsin G and alpha-chymotrypsin was examined. Although synthetic eglin c (41-49) inhibited cathepsin G and alpha-chymotrypsin (Ki = 4.0 x 10(-5) M and 2.0 x 10(-5) M, respectively) but not leukocyte elastase, the synthetic trihexacontapeptide potently inhibited cathepsin G, alpha-chymotrypsin and leukocyte elastase (Ki = 1.8 x 10(-9) M, 1.4 x 10(-9) M and 2.2 x 10(-9) M, respectively). The relationship between the structure of eglin c and the inhibitory activity against the above enzymes is also described.

Amino Acid Sequence↗
PubMed1990

Amino acids and peptides. XXVIII. Synthesis of peptide fragments related to eglin c and studies on the relationship between their structure and effects on human leukocyte elastase, cathepsin G and alpha-chymotrypsin.

Various peptide fragments related to eglin c, which consists of 70 amino acid residues, were synthesized by a conventional solution method and their inhibitory effects on leukocyte elastase, cathepsin G and alpha-chymotrypsin were examined. Among them, H-Arg-Glu-Tyr-Phe-OMe (eglin c 22-25) and H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OMe (eglin c 41-49) inhibited cathepsin G and alpha-chymotrypsin but not leukocyte elastase, while H-Thr-Asn-Val-Val-OMe (eglin c 60-63) inhibited leukocyte elastase but not cathepsin G or alpha-chymotrypsin, although eglin c potently inhibited leukocyte elastase, cathepsin G and alpha-chymotrypsin. These results indicated that the interaction sites of eglin c with leukocyte elastase, cathepsin G and alpha-chymotrypsin might be different.

Amino Acid Sequence↗
PubMed1990

Synthesis of a heptacontapeptide corresponding to the entire amino acid sequence of eglin C.

A heptacontapeptide corresponding to the entire amino acid sequence of eglin c was synthesized by the conventional solution method using a minimal protecting method. The synthetic eglin c exhibited a symmetrical single peak on HPLC at the same retention time as an authentic eglin c, and had the same inhibitory activity against human leukocyte elastase, cathepsin G and alpha-chymotrypsin (Ki = 6.0 x 10(-9) M, 5.5 x 10(-9) M and 2.5 x 10(-9) M, respectively) as N alpha-acetyl-eglin c synthesized genetically (Ki = 5.1 x 10(-9) M, 1.5 x 10(-8) M and 2.2 x 10(-9) M, respectively).

Amino Acid Sequence↗
PubMed1990

Amino acids and peptides. XXIX. Synthesis of peptide fragments related to active center of eglin c and studies on the relationship between their structure and their inhibitory activity against cathepsin G and alpha-chymotrypsin.

H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OMe, corresponding to the sequence 41-49 of eglin c, inhibited human leukocyte cathepsin G and alpha-chymotrypsin. In order to gain further insight into the relationship between the structure and the inhibitory activity against cathepsin G and alpha-chymotrypsin, peptide fragments related to the above nonapeptide were synthesized by a conventional solution method and their inhibitory activities were examined. The smallest peptide which exhibited inhibitory effects on the above enzymes was H-Pro-Val-Thr-Leu-OMe, corresponding to the sequence 42-45 of eglin c.

Amino Acid Sequence↗
PubMed1989

Synthesis of peptide fragments related to eglin c and examination of their inhibitory effect on human leukocyte elastase, cathepsin G and alpha-chymotrypsin.

Various kinds of peptide fragments related to eglin c were prepared by the conventional solution method and their inhibitory effects on human leukocyte elastase, cathepsin G and alpha-chymotrypsin were examined. Peptide (31-40) inhibited cathepsin G (Ki = 2.3 x 10(-4) M), peptide (41-49) potently inhibited cathepsin G and alpha-chymotrypsin (Ki = 4.2 x 10(-5) M and 2.0 x 10(-5) M, respectively), and peptide (60-63) inhibited leukocyte elastase (Ki = 1.6 x 10(-4) M), whereas, peptide (31-35) weakly inhibited both elastase and cathepsin G (Ki = 2.1 x 10(-3) M and 7.3 x 10(-4) M, respectively).

Amino Acid Sequence↗
PubMed1989

Effect of physical training on thrombotic tendency in rats: decrease in thrombotic tendency measured by the He-Ne laser-induced thrombus formation method.

The effect of physical training on thrombotic tendency was assessed in rats. Exercise was done on a flat treadmill for 30 min at a rate of 1,400 m/h (submaximal speed), 5 times a week for either 1.5 or 3 months. The thrombotic tendency was measured by the He-Ne laser-induced thrombus formation method in microvessels of mesentery, i.e. measurement of the number of laser irradiations necessary to induce stasis of blood flow by occlusive thrombus formation. An increase in the number of irradiations necessary to induce occlusive thrombus formation was observed in arterioles, but not in venules after physical training for 1.5 and 3 months.

Animals↗
PubMed1989

Fibrinolytic and amidolytic activities of elastase-and chymotrypsin-like proteases in spleen and leukocytes of some mammals.

Nonplasmin-mediated fibrinolytic activities were extracted with 2 M NaCIO4 from the spleen and leukocytes of nine species of mammals. The amidolytic and fibrinolytic activities of extracts were measured using Suc-Ala-Tyr-Leu-Val-pNA for elastase-like protease (ELP) and Suc-Tyr-Leu-Phe-pNA (or Suc-Ile-Pro-Phe-pNA) for chymotrypsin-like protease (CLP). ELP and the fibrinolytic activity in the human spleen and leukocytes exhibited the highest values among the nine species. The relative order of amidolysis by CLP was as follows: hamster greater than rat greater than mouse greater than dog in the spleen and hamster greater than rat = ox greater than dog in leukocytes. Neither fibrinolytic nor amidolytic activity was measurable in spleens and leukocytes of pigs and rabbits. The ratios of ELP to CLP activity in the spleen or leukocytes of each of the species varied significantly from those observed in humans. The amidolytic activity of the spleen in control mice was low; however, that of mice which had been intraperitoneally inoculated with sarcoma 180 cells was enhanced and further accompanied by an increase in the number of granulocytes and in fibrinolytic activity. These results suggest that the enhancement of spleen amidolytic and fibrinolytic activities is induced by an increase of granulocytes in the circulation.

Animals↗
PubMed1988

Two cases of calcified cysts of the spleen.

Presented in this paper are two cases of calcified cyst of the spleen. The first case is an epidermoid cyst of a 20-year-old male who visited our hospital because of vomiting and epigastric discomfort. The second case is a pseudocyst of a 38-year-old male who was referred to our hospital for evaluation of an abdominal mass. Both patients had no history of abdominal trauma. Linear or curvelinear calcification was revealed in the left epigastric region in the plain X-ray films of the abdomen. Ultrasonography, computed tomography and selective celiac angiography led to the diagnosis of a cyst of the spleen, and surgical operations were performed because the cysts were large and symptomatic. Splenic cyst is a relatively rare disease. However, the cases including asymptomatic cases with small cyst have been increasing in number with the improvement of diagnostic methods and the common use of ultrasonography and computed tomography. In Japanese literatures, 332 cases had been reported by 1983.

Adult↗
PubMed1988

[Mechanisms of gastric mucosal protection in peptic ulcer formation].

The purpose of this study is to investigate the relationship between gastric mucosal blood flow (GMBF) and hydrogen ion back diffusion (HBD) during the formation of acute gastric mucosal lesion (AGML) induced by intragastric instillation of gastric mucosal barrier breakers such as HCl and/or ethanol in rats. By increasing the concentration of HCl and/or ethanol in the test solution, the decrease in GMBF became evident 5 minutes after the instillation. This decrease was parallel with the simultaneous increase in the HBD and HCO3- secretion together with the increase in AGML in a dose-response manner. These findings indicate that promotion of HBD is in fact related to the decrease of GMBF in AGML induced by HCl and ethanol. Furthermore, to evaluate the mechanism of the cytoprotection, the effects of 16, 16-dimethyl prostaglandin E2 (16, 16-dmPGE2) on decreased GMBF and promoted HBD during impairment of the gastric mucosal barrier were assessed. In addition, the amount of acid (HCl) neutralized by HCO3- secretion, which was included in the decrease in the HBD, was determined. Administration of 16, 16-dmPGE2 markedly inhibited the formation of gastric lesions macroscopically, but had no significant effects on decreased GMBF. Though promotion of HBD was also inhibited dose-dependently, the HBD did not recover to that of the control group not treated by ethanol. HCO3- secretion was increased dose-dependently by administration of 16, 16-dmPGE2, and its maximal secretion was 10% of the decrease in the acid by HBD. These results show that cytoprotection by 16, 16-dmPGE2 is strongly related to factors other than the improvement of GMBF, such as inhibition of HBD and stimulation of HCO3- secretion.

Animals↗
PubMed1987

[A pregnant woman with active ulcerative colitis maintained on total parenteral nutrition].

A 28-year-old woman was admitted to our hospital with complaints of mucosanguinous stool and low grade fever. She was diagnosed as a typical chronic continuous type of ulcerative colitis by the findings of barium enema and colonoscopy. Since she had an allergy to sulfasalazine, prednisolone was chosen. She became pregnant during an active stage while being treated with 20 mg of prednisolone a day. Prednisolone was withdrawn to avoid the side-effects of the medicine on the fetal outcome. This resulted in her symptoms becoming far worse and the oral ingestion being discontinued. Total parenteral nutrition (TPN) was required under careful nutritional management. The TPN consisted of glucose, electrolytes, amino acids, vitamins, trace elements and intravenous lipid preparation. Her total energy intake was 2320 kcal a day. Vitamins were administered to her on the bases of the guideline of the American medical association. Rapid turnover proteins, transferrin, vitamins, trace elements and amino acids in addition to routine laboratory tests were measured to estimate her nutritional condition. The data showed that biotin was 10 times lower than the expected value and that other factors were within normal limits. This is the first case in Japan where a woman suffering from an active ulcerative colitis was treated with TPN and delivered of a healthy baby. We concluded that TPN under careful control was useful in the nutritional management and therapy of the pregnant patient who suffered from severe colitis. We believe that the amount of biotin's supplementation should be increased in this type of case because it was 10 times lower than the normal value, although the deficiency symptoms did not develop.

Adult↗
PubMed1987

Increase of nonplasmin fibrinolytic activity in the lung and spleen of streptozotocin-induced diabetic rats.

In streptozotocin-induced diabetes in rats, nonplasmin fibrinolytic activity was found to be significantly increased in the lung and spleen, but not in the liver and kidney. The plasminogen-activator activities, either soluble or insoluble, were almost simultaneously increased in the lung, suggesting the possible release of plasminogen-activator from the lung to the blood. It seems likely that plasminogen-activator of the usual type and nonplasmin protease are also involved in thrombotic disorders in the experimental diabetes.

Animals↗