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D Jin

Publications and source records attributed to D Jin.

At least 19 recordsLinked to original sources

Significance of chymase-dependent angiotensin II-forming pathway in the development of vascular proliferation.

BACKGROUND: Vascular tissues of humans and dogs contain chymase as an angiotensin II-forming enzyme. In this study, we investigated whether chymase-dependent angiotensin II formation plays a crucial role in the development of vascular proliferation in dog grafted veins. METHODS AND RESULTS: The right external jugular vein of dogs was grafted to the ipsilateral carotid artery. As a control group, the right external jugular veins in dogs that had not received grafts were used. In the chymase inhibitor-treated group, the vein was infiltrated with 10 micromol/L Suc-Val-Pro-Phe(P)(OPh)(2) and was grafted to the carotid artery. In the placebo-treated group, ACE activity in the grafted veins was significantly lower than that in the control veins up to 7 days after the operation, whereas chymase activity was increased significantly. After 7 days, the mRNA levels of collagen I, collagen III, and fibronectin, all of which are induced by an increase of angiotensin II action, were significantly increased in the grafted veins, and the intima-media ratio of the grafted veins was also increased. In the chymase inhibitor-treated group, the chymase activity in the grafted veins 7 days after the operation was suppressed to 12.1%. The elevated mRNA levels of fibronectin, collagen I, and collagen III in the grafted veins were significantly suppressed by treatment with the chymase inhibitor, and the intima-media ratio was also decreased significantly. CONCLUSIONS: We demonstrate for the first time that chymase-dependent angiotensin II formation plays an important role in the development of vascular proliferation in the grafted veins.

Angiotensin II↗

Oral administration of a specific chymase inhibitor, NK3201, inhibits vascular proliferation in grafted vein.

Chymase may play an important role in vascular proliferation, as shown by in-vitro experiments, but the role of chymase in vivo has been unclear. In this study, we investigated the effect of a novel chymase inhibitor, NK3201, on this proliferation in dog grafted veins. NK3201 inhibited human and dog chymases, but not rabbit ACE. NK3201 suppressed the Ang I-induced vascular contraction in isolated dog arteries in the presence of an ACE inhibitor, and the IC50 value of chymostatin and NK3201 in dog artery was 320 nM. In dog, the concentration of NK3201 in blood was about 10 microM at 24 h after oral administration of the drug (5 mg/kg). In the group treated with NK3201, each dog was administered orally 5 mg/kg per day from 5 days before to the day before the removal of the grafted veins. Each dog underwent right common carotid artery bypass grafting with the ipsilaterial external jugular vein. By 28 days after grafting, a significant vascular proliferation was observed in the grafted veins and the chymase activity was also increased significantly. Treatment with chymase inhibitor significantly suppressed the proliferation of the grafted veins and the increased chymase activity. In this study, we demonstrate for the first time that oral administration of a specific chymase inhibitor, NK3201, appears useful for preventing vascular proliferation.

Acetamides↗

[Development and clinical application of posterior STBtrade mark thoracolumbar transpedicular screw-plate fixation system].

OBJECTIVE: To develop a posterior STBTM thoracolumbar transpedicular screw-plate system and to apply it clinically. METHODS: A posterior STBTM thoracolumbar transpedicular screw-plate system was developed with titanium alloy (TC4, Ti64A14V) and was used, from December 1999 to July 2000, to treat 63 cases with thoracolumbar or lumbar injuries or diseases, including thoracolumbar fracture/dislocation (33 cases), lumbar spondylosis and spondylolisthesis (16 cases), lumbar spondylosis and disk protrusion (6 cases), degenerative lumbar instability (4 cases), kyphosis due to ankylosing spondylitis (2 cases), and tuberculosis of spine (2 cases). RESULTS: The 33 cases with thoracolumbar fracture/dislocation showed perfect reduction and fixation after the operation. The height of injured vertebral bodies returned to normal. One month later, all patients with neurological deficits, except the 6 cases with neurological deficits of Frankel grade A, showed improvement by 1 approximately 3 Frankel grades. The radicular symptoms in the 26 patients with lumbar spondylolisthesis, lumbar spondylosis and disk protrusion, and degenerative lumbar instability disappeared after operation. Among those cases, complete reduction was achieved in the 7 cases with grade I spondylolisthesis and 7 out of the 9 cases with grade II spondylolisthesis, and incomplete reduction (grade I) was seen in the remaining 2 cases with grade II spondylolisthesis. Forty cases were followed up for 5 months or over in out-patient department, no complication was found. CONCLUSION: The posterior STBTM thoracolumbar transpedicular screw-plate system has the advantages of biological stability, excellent reduction capacity, easiness of operation, and positive clinical effectiveness.

Adult↗

Inhibitory mechanism of daphnodorins for human chymase.

We investigated the inhibitory mechanisms of daphnodorins for human chymase using three-dimensional molecular modeling. In daphnodorin A-human chymase complex, daphnodorin A was fixed to the active site via hydrogen bonds with Ala177, Phe29, and Gly199 in human chymase, and it formed hydrogen bonds with Ser182 and Gly180, and this complex was formed stably. In daphnodorin B-human chymase complex, daphnodorin B formed hydrogen bonds with Lys28 and Phe29 in human chymase, but it could not form hydrogen bonds with Gly199, Ala177, and Lys179. The phenyl group of daphnodorin B shifted from the P1 hole in human chymase in comparison with that of daphnodorin A. For the inhibition of human chymase by daphnodorins, we indicated that it was significant whether daphnodorins formed hydrogen bonds with Ala177 located in the P1 hole, Ser182 located in the active site, Gly180 located in the anion hole, and with Gly199, Phe29, and Lys28 in human chymase.

Benzopyrans↗

12-Hydroxyeicosatetraenoic acid potentiates angiotensin II-induced pressor response in rats.

We studied whether 12-hydroxyeicosatetraenoic acid (HETE) affected the angiotensin II-induced pressor response in rats. After intravenous administration of 1 and 3 microg/kg 12-HETE, the angiotensin II-induced pressor response was not potentiated. However, 10, 20 and 30 min after the administration of 10 microg/kg 12-HETE, the angiotensin II-induced pressor responses were increased by 7.5, 6.8 and 4.8 mm Hg, respectively. The significant pressor response was observed at 10 and 20 min after the administration. In this study, we clearly demonstrated that 12-HETE potentiated the angiotensin II-induced pressor response.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

[The biological function of platelet-derived growth factor-BB in the osteoblast-osteoclast co-culture system].

OBJECTIVE: To investigate the biological effects of platelet-derived growth factor (PDGF)-BB on the osteoclasts in the osteoblast-osteoclast co-culture system. METHODS: The human osteoblasts and osteoclasts were isolated from the iliac crest of patients and co-cultured in the same system. The PDGF-BB or PDGF-BB + NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA) was administered to the co-culture system. The tartrate-resistant acid phosphatase (TRAP) activities in the medium were measured by enzyme kinetics. The resorption pits were stained by toludine blue. The area and number of the resorption pits were determined with the Leica Quantimet 500 system. RESULTS: Under the stimuli of PDGF-BB in the co-culture system, TRAP activities changed from 1.40 U/L +/- 0.12 U/L to 1.46 U/L +/- 0.08 U/L (P > 0.05) in the medium, and the area and number of resorption pits was changed from (427 +/- 149) micrometer(2) and (13.3 +/- 0.9) per slice to (436 +/- 147) micrometer(2) and (14.1 +/- 1.2) per slice respectively (P > 0.05). After the L-NMMA was applied to the system, the TRAP activities rose significantly from 1.46 U/L +/- 0.10 U/L to 2.47 U/L +/- 0.38 U/L along with the increase of dose of PDGF-BB, and the number and area of the resorption pits increased significantly from 436 micrometer(2) +/- 147 micrometer(2) and (14.1 +/- 1.2) per slice to 592 micrometer(2) +/- 171 micrometer(2) and (22.5 +/- 1.7) per slice. Both the TRAP activities and resorption pits rose significantly after the L-NMMA was administered. Comparisons of different treatment groups were made using analysis of variance (ANOVA) with multiple comparisons and a Student-Newman-Keuls test. CONCLUSIONS: The nitric oxide (NO) was produced by osteoblasts stimulated by PDGF-BB in the osteoblast-osteoclast co-culture system. Therefore, the direct promotion effects of PDGF-BB on the osteoclasts were inhibited.

Acid Phosphatase↗

Cilostazol suppresses intimal formation in dog grafted veins with reduction of angiotensin II-forming enzymes.

Cilostazol prevents neointimal formation, but its mechanism has remained unclear. We investigated whether intimal formation in dog grafted veins is suppressed by cilostazol, and studied the effect of cilostazol on angiotensin II-forming enzymes. The external jugular vein was grafted to the carotid artery, and cilostazol (60 mg/kg/day) was administered orally. By 28 days after the surgery, the intimal cross-sectional area of the grafted vein was reduced to 16.7% by treatment of cilostazol, and the activities of angiotensin II-forming enzymes were suppressed significantly. The inhibitory effect of cilostazol in intimal formation may be dependent on inhibition of angiotensin II-forming enzymes.

Angiotensin II↗

R(-)-4-(3-Isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole, a fluorescent chiral tagging reagent: sensitive resolution of chiral amines and amino acids by reversed-phase liquid chromatography.

The usefulness of R(-)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole [R(-)-DBD-PyNCS], a fluorescent chiral tagging reagent, for the determination of racemic amines and amino acids, was studied. The reagent reacted with beta-blockers selected as representative secondary amines to produce corresponding fluorescent diastereomers (excitation at 460 nm and emission at 550 nm). The yields of the derivatization reaction were dependent on the stereostructure arround the NH group in beta-blockers. The resulting diastereomers were completely separated with single chromatographic run using linear gradient elutions by reversed-phase chromatography. R(-)-DBD-PyNCS was also applied to the determination of DL-amino acid, considered to be one of the primary amines, in human urine and foodstuffs. DL-amino acids tested equally reacted with the reagent, and the thiocarbamoyl derivatives were separated with an ODS column. The epimerization during the derivatization reaction was negligible judging from the resolution of opposite diastereomers on the chromatogram. The occurence of D-amino acids (D-Ala, D-Ser, D-Asp and/or D-Glu) was identified in the samples tested. The structures and the purities were elucidated with on-line HPLC-MS. The chiral reagent possessing an isothiocyanate group (-NCS) in the structure seems to be applicable to continuous sequential analysis of peptides containing D-amino acids. The thiocarbamoyl derivatives obtained from the reaction with DL-amino acids were converted to thiohydantoins via thiazolinones in acidic medium. The thiohydantoins produced from acidic, basic, neutral, hydroxyl and aromatic amino acids were completely separated with isocratic elutions using acidic mobile phase containing 0.1% TFA. The separations were sufficient for the identification of DL-amino acid in peptide sequences. Although the epimerization during the conversion reaction to thiohydantoins was not avoidable, the descrimination of D- and L-configuration was demonstrated with some commercially available peptides such as beta-lipotropin and [D-Ala2]-deltorphin II. The Edman degaradation method using R(-)-DBD-PyNCS was also adopted to autoanlaysis by gas-phase sequencer. The separation and the detection (UV 254 nm) conditions of the derivatives were used without any change from those for the Edman degradation method using PITC as the tagging reagent. The three DL-amino acid residues (Tyr, Ala and Gly) in [L-Ala2]-leucine-enkephalin and [D-Ala2]-leucine-enkephalin were perfectly identidied with the autoanalysis.

Amines↗

A simple flow-injection on-line clean-up system for microwave plasma-torch atomic emission spectrometry.

A simple flow injection (FI) on-line clean-up system has been developed for microwave plasma-torch atomic emission spectrometry (MPT-AES). A non-selective strongly acidic cation-exchange resin was used to achieve the goal of "on-line clean-up". Ag and Zr, which form halogen-complex anions in halide acid media, and Cr, Mo, and P, which exist as acid group anions or acids (neutral) in acidic solution, were determined and the interfering matrix cations were removed on-line. Satisfactory analytical results were obtained from some practical samples by use of this procedure.

Journal Article↗

Different angiotensin II-forming pathways in human and rat vascular tissues.

We studied the angiotensin II-forming pathways in extracts from human and rat vascular tissues. In the extract from human artery, angiotensin I mainly converted to two products, angiotensin-(1-9) and angiotensin II, while in the extract from rat artery, the major angiotensin I products were angiotensin II and angiotensin-(5-10). The concentrations of angiotensin II and angiotensin-(1-9) generated in the human extract (1 mg protein/ml) after incubation for 30 min were 3.2 and 2.5 nmol, respectively, and that of angiotensin II and angiotensin-(5-10) generated in the rat extract (1 mg protein/ml) were 0.28 and 2.3 nmol, respectively. In the extract from human vascular tissues, the angiotensin II formation was inhibited by 8% with lisinopril and by 95% with chymostatin. The other product, angiotensin-(1-9) was inhibited completely by carboxypeptidase inhibitor. In the extract from rat vascular tissues, the angiotensin II formation was suppressed to 4% by lisinopril, but not by chymostatin. The angiotensin-(5-10) formation was completely inhibited by chymostatin. These findings suggest clearly that human vascular tissues contain two angiotensin II-forming enzymes, angiotensin-converting enzyme and chymase, but rat vascular tissues have no chymase-dependent angiotensin II-forming pathway.

Adult↗

Chymase-dependent angiotensin II formation in the saphenous vein versus the internal thoracic artery.

OBJECTIVES: The great saphenous vein graft is known to be less patent than the internal thoracic artery graft. Recently, we reported that chymase-dependent angiotensin II formation plays an important role in the development of intimal hyperplasia in dog grafted veins. In this study we investigated the levels of angiotensin II-forming enzymes, angiotensin-converting enzyme, and chymase in human saphenous veins and internal thoracic arteries. METHODS: The saphenous vein and internal thoracic artery specimens were obtained from coronary artery bypass grafts of patients during surgical procedures (saphenous vein, n = 16; internal thoracic artery, n = 16). Activities of angiotensin-converting enzyme and chymase were determined by using the extract from the saphenous vein or internal thoracic artery. Sections of the saphenous vein or internal thoracic artery were stained with van Gieson's elastin stain and were immunostained with anti-human chymase antibody. RESULTS: The activities of angiotensin-converting enzyme in the saphenous vein and internal thoracic artery were 0.34 +/- 0.12 and 0.32 +/- 0.17 mU/mg protein, respectively, and the difference was not significant. The chymase activity in the saphenous vein was significantly higher than that in the internal thoracic artery (saphenous vein, 10.1 +/- 0.81 mU/mg protein; internal thoracic artery, 6.21 +/- 1.86 mU/mg protein). Chymase-positive cells in the saphenous vein were located in both the media and adventitia, and those in the internal thoracic artery were located only in the adventitia. The number of chymase-positive cells in the saphenous vein was about 2.6 times that in the internal thoracic artery. CONCLUSION: The chymase activity, but not the angiotensin-converting enzyme activity, was significantly higher in the saphenous vein, suggesting that the high levels of chymase activity may be related to the poorer performance of the saphenous vein for use as a bypass conduit.

Aged↗

An orally active chymase inhibitor, BCEAB, suppresses heart chymase activity in the hamster.

We investigated the effects of a novel chymase inhibitor, BCEAB (4-[1-[[bis-(4-methyl-phenyl)-methyl]-carbamoyl]-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid). The IC50 value of BCEAB for purified human chymase was 5.4 nM, whereas BCEAB did not inhibit the angiotensin-converting enzyme, elastase and tryptase. In isolated dog arteries, the IC50 value of BCEAB for the angiotensin I-induced contraction in the presence of 1 microM lisinopril was 2.8 microM. In the hamster, the heart chymase activities were significantly suppressed to 42.0% and 26.9% 3 h after oral administration of 100 and 300 mg of BCEAB/kg of body weight, respectively. In conclusion, BCEAB is a useful chymase inhibitor for studying the role of chymase in vivo.

Angiotensin II↗

Possible roles of cardiac chymase after myocardial infarction in hamster hearts.

The significance of cardiac chymase after myocardial infarction (MI) was evaluated using a hamster model of MI. At 1, 3, 7, 14, 28 and 56 days after MI, tissues were removed for measurements of angiotensin-converting enzyme (ACE) and chymase activities. The mean infarct size 3 days after left coronary artery ligation was 47.3 +/- 5.9% of the left ventricle circumference. The ratio of left ventricle weight to body weight was significantly increased from 3 days after MI. The level of plasma renin activity in the MI hamsters was significantly increased at the early phase of MI (1-3 days), while no significant changes in plasma ACE activity were observed. The ACE activity in the infarcted left ventricle was significantly increased starting from 3 days after MI and this increase was sustained up to 28 days. The chymase activity in the infarcted left ventricle was significantly increased starting from 1 day after MI and this increase was sustained up to 56 days. The number of chymase-positive mast cells in the infarcted left ventricle was significantly higher than in the sham group 3 and 7 days after operation. Treatment with an angiotensin (Ang) II type 1 receptor antagonist (candesartan cilexetil, 10 mg/kg per day) starting 3 days before the induction of MI significantly reduced the mortality rate during 14 days of observation following MI, whereas treatment with an ACE inhibitor (lisinopril, 20 mg/kg per day) did not. A significant improvement in hemodynamics (maximal negative and positive rates of pressure development, left ventricular systolic pressure and end-diastolic pressure, mean arterial blood pressure) was observed by the treatment with candesartan cilexetil, but not with lisinopril, 3 and 14 days after MI. These results suggested that Ang II produced by chymase may participate in the pathophysiologic state after MI in hamsters.

Angiotensin Receptor Antagonists↗

Multiple pathways of angiotensin I conversion and their functional role in the canine penile corpus cavernosum.

Multiple pathways of angiotensin (Ang) I conversion and their functional role in the canine penile corpus cavernosum were investigated. Biochemical analysis revealed high activities of angiotensin-converting enzyme (ACE) (6.9 +/- 1.7 mU/mg of protein, mean +/- S.E.M., n = 8) and chymase-like enzyme (4.0 +/- 1.4 mU/mg of protein). Functional recording of isometric tension showed that Ang I (3 x 10(-7) M) induced a tension of 0.17 +/- 0.05 g (n = 5), which was reduced to about 60% by pretreatment with an ACE inhibitor, lisinopril (10(-6) M), and almost completely blocked by lisinopril in combination with a chymase inhibitor, chymostatin (10(-4) M). Binding sites for ACE and Ang II receptors were studied by in vitro autoradiography using 125I-351A and 125I-[Sar1, Ile8]Ang II as ligands, respectively. Dense binding of ACE appeared in the endothelial layer of the corpus cavernosum penis, and Ang II receptors were localized in the trabecular smooth muscle layer. An AT1 receptor antagonist, CV-11974 (10(-6) M), markedly displaced 125I-[Sar1, Ile8]Ang II bindings, indicating that the corpus cavernosum penis contains AT1 receptors exclusively. Immunohistochemical studies demonstrated ACE in the endothelium of the corpus cavernosum penis. Mast cells that produce chymase were present mainly in the cavernosal area. These results demonstrate that chymase, in addition to ACE, is involved in the contraction of canine penile corpus cavernosum through local Ang II formation.

Angiotensin I↗

[Anterior thoracolumbar K-plate fixation system: design and clinical application].

OBJECTIVES: To develop an anterior thoracolumbar K-plate fixation system and to report its preliminary clinical application. METHODS: The K-plate system was developed with titanium alloy(TC4, Ti6A14V) and self-locking screw design was used. In 23 cases treated with this system, 13 had thoracolumbar fracture, 9 tuberculosis, and back syndrome after lumbar TFC operation. RESULTS: All the 23 cases were followed up for one to ten months, averaging 4.5 months. In the 13 cases of fracture, body height of injured vertebra were regained completely, and neurologic deficits improved 2.1 grades in Frankel scale. In the 9 cases of tuberculosis, neurologic functions recovered and no local recurrence was noted. In one case of back syndrome, symptoms and signs did not occur after anterior TFC removal, interbody fusion, and K-plate fixation. This patient received second operation to remove K-plate 3 months after solid osseous fusion, and no electric erosion or obvious tissue reaction was found. 18 of the 23 cases were followed up for four months or more, and solid fusion was found in these patients in three to four months after surgery. No early complications related to implant were noted during the follow-up. CONCLUSION: This K-plate system is suitable for reconstruction of thoracolumbar stability after anterior decompression in indicated patients.

Adult↗

[The relationship between angiotensin converting enzyme gene polymorphism and risk factors for cerebral infarct].

OBJECTIVE: To explore the relationship between angiotensin converting enzyme (ACE) gene polymorphism and risk factors of cerebral infarct (CI) in Chinese Han nationality. METHODS: One hundred and sixty-five cases with cerebral infarct, 101 cases of essential hypertension patients with 106 normal persons in Chinese Han serving as controls were detected using polymorase chain reaction (PCR) and genetic methods. ACE contents in serum were measured by colorimetric method. Risk factors of cerebral infarct were assessed by standard questionnaire, physical examination and blood tests. RESULTS: ACE DD genotype appeared more common in patients of cerebral infarct when comparing with essential hypertension groups (0.43 versus 0.31, chi 2 = 4.03, P < 0.05) and normal controls (0.43 versus 0.17, chi 2 = 19.86, P < 0.01). D:I allele frequency appeared to be 0.66:0.34 in cerebral infarct patients and 0.41:0.59 in controls (chi 2 = 32.85, P < 0.01). In basal ganglia infarct and thalamus infarct groups, ACE DD genotype and allele ratio distribution were remarkably different to that in normal subjects (chi 2 = 18.30, 12.41, P < 0.01). The mean levels of serum in cerebral and hypertension were higher than in normal controls (F = 2,240.06, P < 0.01), and serum ACE activity in ACE DD genotype was significantly higher than that in ACE DI and II genotype in cerebral group (F = 8.83, P < 0.01). CONCLUSIONS: The ACE gene deletion polymorphism might serve as an independent risk factor for cerebral infarct in Chinese Han nationality while circulation ACE activity might be related to gene deletion polymorphism.

Adult↗

Angiotensin II receptor antagonist, L-158,809, prevents intimal hyperplasia in dog grafted veins.

We investigated the levels of the angiotensin II-forming enzymes, chymase and angiotensin converting enzyme (ACE), in dog grafted veins, and studied the effect of an angiotensin II type 1 receptor antagonist, L-158,809, on vascular proliferation in the grafted veins. The right external jugular vein was grafted to the ipsilaterial carotid artery. In the group treated with L-158,809, the drug (10 mg/kg per day, p.o.) were administered orally from 7 days before the operation to 28 days after it, while the others were administrated placebo. In the placebo-treated group, the chymase activity in the grafted veins was increased about 10-fold and the ACE activity was doubled. The areas of intima and media were significantly increased in the grafted veins in the placebo-treated group. L-158,809 significantly reduced the intimal area of the grafted veins. An angiotensin II receptor antagonist, L-158,809, prevented the vascular proliferation in the grafted veins, and the development of the proliferation may depend on activation of local angiotensin II formation.

Angiotensin II↗

A topological study of the human gamma-glutamyl carboxylase.

gamma-Glutamyl carboxylase (GC), a polytopic membrane protein found in the endoplasmic reticulum (ER), catalyzes vitamin K-dependent posttranslational modification of glutamate to gamma-carboxyl glutamate. In an attempt to delineate the structure of this important enzyme, in vitro translation and in vivo mapping were used to study its membrane topology. Using terminus-tagged full-length carboxylase, expressed in 293 cells, it was demonstrated that the amino-terminus of the GC is on the cytoplasmic side of the ER, while the carboxyl-terminus is on the lumenal side. In addition, a series of fusions were made to encode each predicted transmembrane domain (TMD) followed by a leader peptidase (Lep) reporter tag, as analyzed by the computer algorithm TOPPRED II. Following in vitro translation of each fusion in the presence of canine microsomes, the topological orientation of the Lep tag was determined by proteinase K digestion and endoglycosidase H (Endo H) cleavage. From the topological orientation of the Lep tag in each fusion, the GC spans the ER membrane at least 5 times, with its N-terminus in the cytoplasm and its C-terminus in the lumen.

Animals↗