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Biomedical subjects

H Lu

Publications and source records attributed to H Lu.

At least 415 records · Page 23Linked to original sources
PubMed1994

Postoperative hemostasis and fibrinolysis in patients undergoing cardiopulmonary bypass with or without aprotinin therapy.

Intra- and postoperative blood loss during open heart surgery is reduced by approximately 50% when aprotinin, a potent inhibitor for plasmin and kallikrein, is administered during surgery. But whether aprotinin increases the risk of thrombotic complications remains controversial. The aim of this study was to evaluate the effects of aprotinin administration on coagulation and fibrinolysis during and after cardiopulmonary bypass (CPB). Thirty patients undergoing CPB were randomly assigned to two comparable groups for a double-blind study (16 patients receiving high-dose aprotinin, 14 patients receiving placebo). Patients' plasma levels of ATM (thrombin-induced modified antithrombin III), FbDP (fibrin degradation products, D-Dimers), t-PA (tissue-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) were measured at regular intervals. In both groups, ATM level increased during surgery (from less than 30 to 90-110 ng/ml) and returned to normal 24 h after surgery and remained unchanged thereafter. Aprotinin reduced this increase in ATM levels (p = 0.02 at 30 min after the start of CPB). The FbDP generated during surgery was greatly reduced in the aprotinin group (945 ng/ml) in comparison with the placebo group (1889 ng/ml, p = 0.004). After surgery, FbDP levels decreased in both groups with nadirs at 2nd day (placebo group: 940 ng/ml and aprotinin group: 865 ng/ml) indicating a hypofibrinolytic period. Then, the FbDP level in both groups started to increase up to the 9th day, in an identical manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Leishmaniasis in Karamay. XIV. Identification of promastigote isolates from naturally infected Phlebotomus major wui].

Phlebotomus major wui, an anthropophilic species, was predominant among sandflies in Karamay, Xinjiang of China. The females of this species collected in the wild and houses were detected to be infected with promastigotes. Three isolates of promastigotes obtained from P. major wui were inoculated intraperitoneally and subcutaneously into normal hamsters or BALB/c mice which developed visceral leishmaniasis later. The mean size of amastigotes in hamster viscera (smear observation) artificially inoculated with the cultured parasite originated from sandfly was significantly smaller than those in control hamster inoculated with the cultured Leishmania turanica from great gerbils in situ. The promastigotes from P. major wui hardly grew in NNN medium. In addition, 32P labeled gene gp63 was used as probe to hybridize DNA prepared from L. infantum, L. turanica and Leishmania from this sandfly showed that marked homogeneity existed between the isolates from P. major wui and L. infantum. At the present time, visceral leishmaniasis did not occur in Karamay but cutaneous leishmaniasis (CL) has been evidenced. Thus, what is the source of natural infection of P. major wui? Whether L. turanica or L. infantum is the pathogen of human CL in this area? These are interesting aspects to deal with in the further study.

Animals↗
PubMed1994

[Effects of nifedipine on hepatic hyaluronic acid, hydroxyproline and glucosaminidase contents in rats with liver fibrosis].

In early stage treatment groups, Nifedipine (Nif) could significantly reduce hepatic hyaluronic acid (HA) and hydroxyproline (Hyp) contents in rats in which liver fibrosis had been induced by CCl4 treatment. N-acetyl-beta-glucosaminidase (beta-NAG) activity showed a similar change in the high dosage group. In late stage treatment groups, HA was reduced markedly, and decreased beta-NAG levels were noted in the high dosage group. These effects on HA, Hyp and beta-NAG were dependent on Nif dosage. The results suggest that Nif could inhibit the development of liver fibrosis in rats, and may even reverse it.

Acetylglucosaminidase↗
PubMed1994

[Long-term effect of the modified type-III tympanoplasty].

Tympanoplasty using reconstructed ossicular chain from auto and foreign rib cartilages were performed on 264 ears with missing malleus. The postoperative follow-ups have been made in 102 ears with auto cartilage for 5-6 years and in 162 ears with foreign cartilage more than 4 years. The hearing level of 79 ears in the former (77.4%) and 124 ears in the latter (76.5%) have been enhanced by 15 dB or to applied hearing level. Long-term hearing improvement was satisfactory. The characteristics of the surgical methods was discussed.

Adolescent↗
PubMed1993

The plasminogen-activation system in ovarian tumors.

We studied the plasminogen activation system in tumor tissue by measuring the antigen level of the 2 plasminogen activators, tissue-type (t-PA) and urokinase-type (U-PA) and their inhibitors, plasminogen-activator inhibitors type-I (PAI-I) and type-2 (PAI-2) in the tissue extracts of 43 human benign and malignant ovarian tumors. U-PA levels were significantly higher in malignant than in benign tumors. In addition, U-PA antigen levels were higher in the metastatic tissue of advanced disease (FIGO stage III) than in the primary localized tumor (FIGO stage I/II). Also PAI-I concentrations tended to be higher in malignant than in benign tumors, but this difference was not statistically significant. In contrast, t-PA levels were lower in metastatic than in non-metastatic tumors, whereas PAI-2 levels were unrelated to the stage of ovarian malignancy. These results were integrated in a plasminogen-activation-dependent malignancy index (U-PA x PAI-I/t-PA). This index distinguished the different groups of benign ovarian tumors, localized and metastatic ovarian carcinomas better than U-PA levels. It could be useful as a prognostic indicator in ovarian cancer.

Carcinoma↗
PubMed1993

Cloning and characterization of a human protein phosphatase 1-encoding cDNA.

While sequence information is available for a number of eukaryotic protein phosphatase 1 (PP1)-encoding genes, the cloning and characterization of a complete human pp1 gene has not been reported. We have used two conserved regions within the pp1 family of genes to synthesize oligodeoxyribonucleotide primers for the amplification of a 438-bp sequence from human mRNA. This DNA fragment was sequenced to verify that it corresponded to a pp1 cDNA and it was used to screen a human cDNA library to isolate a full-length clone. The deduced amino acid (aa) sequence identified a protein of 330 aa in length. Comparison with the rabbit pp1 cDNA sequence showed some nucleotide differences, largely at the third position of the codon, with complete concordance at the aa level. Northern blot analysis revealed an mRNA of approximately 1.6 kb.

Amino Acid Sequence↗
PubMed1993

Comparative study of fibrinolytic activity on 937 line after stimulation by interferon gamma, 1,25 dihydroxyvitamin D3 and their combination.

Previous study showed that the secretion of urokinase (UK) by monoblastic cell line U 937 and the number of binding sites for urokinase and for plasminogen (Plg) on the cell surfaces were augmented by interferon gamma (INF tau). This induction led to an increase in fibrinolytic activity on cell surfaces. A similar increase was also observed when treating the U 937 cells with 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3. Here we report that the combination of these two agents induced a 2.7 fold increase in the plasminogen activator activity on U 937 cell surfaces in comparison with 1 fold increase induced by INF tau and 1.3 fold increase by 1,25(OH)2D3. As evaluated by a flow cytometer, the increased fibrinolytic activity induced by the combination of INF tau and 1,25(OH)2D3 could be attributed to the increase of the number of binding sites both for UK (3.7 x 10(4) vs 1.2 x 10(4) per cell) and for Plg (16.2 x 10(4) vs 3.6 x 10(4) per cell), accompanied by an increased expression of CD 14, which is an antigen of differentiation on cell surfaces. These results suggest that the expression of urokinase receptors and plasminogen receptors may be coupled together by unknown intracellular mechanisms during cell differentiation, and support the idea that the concomitant regulation of these two receptors for UK and Plg is an important aspect in cell associated-fibrinolytic activity.

Calcitriol↗
PubMed1993

Activation of the 92 kDa type IV collagenase by tissue kallikrein.

Type IV collagenases are secreted as latent 92 and 72 kDa proenzymes which are then activated extracellularly. The mechanisms by which they are activated in vivo are not clear. We have studied the activation of porcine endothelial cell type IV collagenases by tissue and plasma kallikrein, and found that tissue kallikrein was a very efficient activator of the 92 kDa type IV collagenase. Enzyme cleavage was observed at concentrations of tissue kallikrein as low as 0.1 microgram/ml. Plasma kallikrein had no effect. By comparison, plasmin, which has been proposed to be the physiological activator of interstitial collagenase and stromelysin, and elastase were much less effective, and high concentrations (plasmin at 100-200 micrograms/ml and elastase at 20 micrograms/ml) were required to cause only a limited cleavage which was not associated with an increase in activity, as observed by the gelatin-gel lysis assay. In addition tissue kallikrein was found by immunohistochemistry to be present in the extracellular matrix of the intima of porcine aortic vessel wall. These findings suggest that tissue kallikrein can be a potential activator of the 92 kDa type IV collagenase in vivo.

Animals↗
PubMed1993

Functional evaluation of intrathoracic versus extrathoracic skeletal muscle ventricles.

Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in 10 dogs. In Group I (n = 5), SMVs were left in an extrathoracic position on the chest wall. In Group II (n = 5), SMVs were placed within the chest cavity. After a 3- to 4-week vascular delay period, SMVs were electrically preconditioned with 2 Hz continuous stimulation for 6 weeks. At a second procedure, SMVs were connected to a mock circulation system, and function was evaluated under differing conditions of preload and afterload. SMVs in Group II were significantly more compliant, as demonstrated by the end diastolic pressure volume relationship, than those in Group I (P < 0.01). SMVs in Group II were also capable of generating greater stroke work than those in Group I (P < 0.05). SMVs in Group II were also capable of greater stroke work than those in Group I at physiologic preloads (P < 0.05). These findings suggest that SMVs placed in an intrathoracic position exhibit better diastolic and systolic function.

Animals↗
PubMed1993

Double cardiomyoplasty: acute versus chronic results.

We previously found that double cardiomyoplasty using both acutely raised, unconditioned latissimus dorsi muscles increased cardiac output by 9.6% (1,547 +/- 154 versus 1,695 +/- 166 mL/min), stroke volume by 18.2% (12.1 +/- 0.6 versus 14.3 +/- 0.7 mL), peak left ventricular pressure by 18.4% (98 +/- 3 versus 116 +/- 5 mm Hg), and peak right ventricular pressure by 62.5% (24 +/- 2 versus 39 +/- 4 mm Hg) (p < 0.05 for all differences). In this study 10 dogs underwent double cardiomyoplasty: 3 died perioperatively, and 7 underwent 8 weeks of muscle conditioning. After the conditioning period, the muscle flaps did not contract in 2 of the 7 dogs. Hemodynamics were measured in the remaining 5 dogs. Using fatigue-resistant muscle, cardiac output decreased by 3.7% (1,279 +/- 262 versus 1,233 +/- 274 mL/min), stroke volume decreased by 9.0% (9.5 +/- 1.2 versus 8.8 +/- 1.2 mL), and peak left ventricular pressure increased by 10.6% (82.1 +/- 6.5 versus 90.8 +/- 3.2 mm Hg), but not significantly. Peak right ventricular pressure increased significantly by 31.3% (24.3 +/- 2.1 versus 31.9 +/- 3.6 mm Hg; p < 0.05). Hemodynamic effects of individual left or right muscle contractions versus bilateral muscle stimulation were not significantly different except for a greater percentage increase in peak right ventricular pressure (right, 24.9 +/- 2.1 mm Hg unstimulated versus 28.0 +/- 2.1 stimulated; left, 26.3 +/- 0.9 mm Hg unstimulated versus 30.7 +/- 2.4 mm Hg stimulated; bilateral, 24.3 +/- 2.1 mm Hg unstimulated versus 31.9 +/- 3.4 mm Hg stimulated; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Skeletal muscle ventricles: left ventricular apex to aorta configuration.

Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in 6 dogs. After 3 weeks of vascular delay followed by 6 weeks of 2-Hz continuous electrical conditioning, a valved conduit was placed between the left ventricular apex and the SMV and a second valved conduit, between the SMV and the aorta. The SMV was stimulated to contract during diastole at a 1:2 ratio with the heart. The SMV pumped 47% of the systemic blood flow initially (0.73 +/- 0.23 versus 1.54 +/- 0.42 L/min) and 40% after 3 hours. Skeletal muscle ventricle stimulation resulted in a 58% increase in mean diastolic pressure initially (52 +/- 9 to 82 +/- 11 mm Hg; p < 0.05) and a 73% increase (45 +/- 7 to 78 +/- 8 mm Hg) after 3 hours of continuous pumping. This was associated with a 68% increase in the endocardial viability ratio initially and a 63% increase at 3 hours. The systolic tension-time index decreased by 26% initially and 25% at 3 hours. This study indicates that the SMV configuration of left ventricular apex to aorta may be particularly suitable for left ventricular assist.

Animals↗
PubMed1993

Endothelial cell proteases: physiological role and regulation.

Endothelial cell-derived proteases can be classified according to their physiological role. The proteases involved in extracellular matrix degradation are important in endothelial cell migration and thereby in angiogenesis. They include the urokinase-type plasminogen activator (uPA) and the metalloproteases, collagenases, gelatinases and stromelysin. uPA secreted from endothelial cells remains associated with the cell membrane, on specific receptors localized in the vicinity of the receptors for plasminogen. This favours the local activation of plasminogen into plasmin. Plasmin, generated on the cell surface, is fully active as it is not inhibited by alpha 2-antiplasmin. Plasmin acts directly by degrading some components of the extracellular matrix and indirectly by activating the prometalloproteases. Secretion of PAI by migrating cells is generally stimulated by the same factors that induce uPA secretion, limiting the degradation of the matrix to the pericellular path. The degradation of the fibrin clot involves the tissue-type plasminogen activator tPA, which like the uPA activates plasminogen to plasmin. This system is also regulated by two different mechanisms. On the one hand, fibrin itself favours its own degradation by formation of a ternary complex, fibrin-plasminogen-tPA, in which the affinity of tPA for plasminogen is markedly increased, as compared to the affinity of unbound tPA. In addition, plasmin generated on the clot is protected from inhibition by alpha 2-antiplasmin. On the other hand, as for uPA, tPA is inhibited by PAI-1. The importance of the regulation of this system is illustrated by the thrombotic risk observed when there is either a decrease in tPA or an increase in PAI-1, and inversely by haemorrhages in the case of increase in tPA.

Animals↗
PubMed1993

The protection by ischemic preconditioning against myocardial ischemia- and reperfusion-induced arrhythmias is not mediated by ATP-sensitive potassium channels in rats.

BACKGROUND: Single or multiple brief periods of myocardial ischemic preconditioning (PC) limits ischemia- and reperfusion-induced arrhythmias. This study tested whether PC protects against ischemia/reperfusion-induced arrhythmias and, if so, whether the protective effect was mediated by the opening of ATP-sensitive (KATP) channels. METHODS: In protocol 1, the effects of PC (three cycles of 2 minutes of coronary occlusion and 5 minutes of reperfusion) on the development of arrhythmias after a coronary occlusion of 5, 10, or 20 minutes followed by 10 minutes of reperfusion were studied in rats. In protocol 2, solvent or a KATP channel blocker (glyburide [0.64 mg/kg body weight delivered intravenously]) was administered 5 minutes before PC. In a second group, glyburide was administered immediately after PC. In a third group, solvent, glyburide, or a KATP channel opener (pinacidil [0.16 mg/kg delivered intravenously]) was administered 5 minutes before coronary occlusion for 5 minutes without PC. RESULTS: In protocol 1, PC significantly reduced the ischemia-induced ventricular premature beats (VPBs) and ventricular tachycardia (VT), and it abolished ischemia-induced ventricular fibrillation (VF) during 10 or 20 minutes of coronary artery occlusion. PC also significantly reduced reperfusion-induced ventricular arrhythmias after 5 or 10 minutes of coronary artery occlusion; this effect of PC, however, was lost during reperfusion after 20 minutes of coronary occlusion. In protocol 2, PC again produced a marked reduction in reperfusion-induced arrhythmias and abolished the incidence of VPBs during 5 minutes of ischemia as well as the incidence of irreversible VF during reperfusion, whereas glyburide did not block the protective effect of PC on ischemia- and reperfusion-induced arrhythmias. Glyburide administered in non-PC animals did not reduce ischemia- and reperfusion-induced arrhythmias, nor did pinacidil. CONCLUSIONS: The protective effect of PC was not attenuated by glyburide. These results suggest that the protective effect of PC in ischemia- and reperfusion-induced arrhythmias is not likely to be related to activation of KATP potassium channels during ischemia in rats.

Adenosine Triphosphate↗
PubMed1993

Reversibility of thrombin-induced decrease in platelet glycoprotein Ib function.

Thrombin induces a redistribution of glycoprotein (GP) Ib/GP IX complex from the platelet surface into the surface connected canalicular system (SCCS). This redistribution results in a reduced interaction of platelet GP Ib with von Willebrand factor (vWF) bound to subendothelium leading to impaired platelet adhesion. In this study we show that the platelet aggregation and degranulation require concentrations of thrombin above 0.05 U/ml, while the decrease in GP Ib function (about 50% of control value), as determined by ristocetin induced platelet agglutination, can be induced by lower concentrations (0.01-0.04 U/ml). Moreover, we show that when adding thrombin inhibitors to the platelets preincubated with < 0.04 U/ml thrombin for 5 min, their agglutinability by ristocetin was gradually recovered within 30 min, indicating that in these conditions the decrease in platelet adhesiveness is reversible. Immuno-electromicroscopic study showed that this restoration of platelet GP Ib function was associated with a reversed translocation of GP Ib from the SCCS to the plasma membrane. The data obtained from counting gold particles showed that the ratio of GP Ib immunolabelling on the external membrane versus that on the SCCS was 3.31 +/- 0.90 for resting platelets, down-regulated to 0.84 +/- 0.13 (P < 0.05 versus resting platelets) for the platelets treated with 0.04 U/ml thrombin and returned to 2.63 +/- 2.21 (P > 0.05 versus resting platelets) after incubation for 30 min with hirudin. However, the translocation of GP Ib was poorly reversed by thrombin inhibitors when higher concentrations of thrombin were used which induced platelet aggregation and large extent of degranulation. We conclude that thrombin affects platelets in a dose dependent manner, and that at low concentrations the decrease in platelet GP Ib related function is a reversible phenomenon.

Antithrombins↗
PubMed1993

Reversible translocation of glycoprotein Ib in plasmin-treated platelets: consequences for platelet function.

Understanding the effect of fibrinolysis on platelet function is of clinical importance. Plasmin is recognized to affect platelet adhesive function by reducing the interaction of platelet glycoprotein (GP) Ib with von Willebrand factor (vWF) bound to the subendothelium. This platelet function is commonly explored in vitro by the ristocetin-induced agglutination test. Our previous study demonstrated a plasmin-induced redistribution of GP Ib molecules from the platelet surface to the linings of the surface-connected canalicular system (SCCS), a critical mechanism for understanding plasmin-induced GP Ib dysfunction. Here, we demonstrate that neutralization of plasmin by its inhibitors, aprotinin or tripeptide Val-Phe-Lys-CH2Cl, permits a time dependent recovery (within 30 min) of ristocetin-induced agglutination in the platelets which were stimulated by plasmin at < 1 CU ml-1. This functional recovery was accompanied with a restoration of a normal amount of GP Ib on the platelet surface, as measured by the binding of both monoclonal anti-GP Ib antibody SZ 2 and 125I-labelled vWF to the platelets. Cytochalasin D did not inhibit this recovery, suggesting that this process may be due to passive actin depolymerization. These findings were further confirmed by immunoelectron microscopic study. Utilizing the platelets pre-labelled with anti-GP Ib antibody prior to plasmin stimulation, it was demonstrated that the observed recovery is due to a reverse translocation from the SCCS to the plasma membrane of the same GP Ib molecules which were present initially at the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Agglutination↗
PubMed1993

Skeletal muscle ventricles with efferent valved homograft.

Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in seven beagles. Following 3 weeks of vascular delay and 6 weeks of electrical conditioning, the SMVs were connected in series with the thoracic aorta using a valved aortic homograft for the efferent limb. The SMVs were stimulated to contract synchronously during diastole. Effective aortic diastolic counterpulsation was achieved in all dogs, with an average 24.2% +/- 15.3% improvement in diastolic pressure. In two animals surviving beyond 3 months, increase in SMV function was noted over time. Appropriate aortic homograft valve function was documented by echocardiogram. Acute reversible heart failure was induced with propranolol in one dog alive after 126 days. A 61.3% reduction in cardiac output and a 37.6% reduction in mean arterial blood pressure were achieved. During profound low cardiac output, SMV stimulation with 33 Hz and 50 Hz improved cardiac output by 16.9% and 17.8%, improved the tension time index by 14.9% and 16.1%, and improved the endocardial viability ratio by 34.1% and 34.1%, respectively. These results again demonstrate the long-term effectiveness of SMVs as aortic counterpulsators. A valve in the efferent limb of the SMV system functions appropriately over time and may improve the efficiency of the system.

Animals↗