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Biomedical subjects

H Lu

Publications and source records attributed to H Lu.

At least 451 records · Page 25Linked to original sources
PubMed1991

Anthracycline immunoconjugates prepared by a site-specific linkage via an amino-dextran intermediate carrier.

Anthracycline, either daunomycin or doxorubicin, was site specifically attached to the carbohydrate moiety of a monoclonal anticarcinoembryonic antigen antibody by using amino-dextran as the intermediate carrier. The reaction resulted in an immunoconjugate that contains approximately 20 to 25 molecules of drug per molecule of immunoglobulin G. Flow-cytometric studies revealed the retention of the antibody-binding activity. The immunoconjugate was cytotoxic to the target cells, as examined by the 75selenomethionine incorporation studies, and remained efficient for targeting a human colonic tumor (GW-39) in the nude mouse model. The conjugate possessed a greater antitumor activity against the subcutaneous tumor than either the free drug or an irrelevant antibody conjugate, and it was well tolerated by the animals at a much higher dose level than was the unconjugated drug.

Animals↗
PubMed1991

Temperature dependence of plasmin-induced activation or inhibition of human platelets.

It is known that at 37 degrees C plasmin may have two opposite effects on platelets: at high concentrations (greater than 1.5 caseinolytic units [CU]/mL), plasmin activates platelets; at lower concentrations (0.1 to 1.0 CU/mL) it inhibits platelet activation induced by thrombin, collagen, or calcium ionophore A23187. In this study, we report that when lowering the incubation temperature to 22 degrees C, plasmin at low concentrations (0.1 to 0.5 CU/mL) fully activated platelets. When platelets were treated with 0.2 CU/mL of plasmin, lowering the incubation temperature from 37 degrees C to 22 degrees C resulted in an increase in the expression of fibrinogen receptors, in platelet release and aggregation. Thromboxane A2 was not generated by plasmin treatment at either temperature. Ultrastructural studies showed that platelets responded to low-dose plasmin at 37 degrees C by forming pseudopods, centralizing granules without fibrinogen release, whereas at 22 degrees C the same dose of plasmin caused platelet degranulation with the appearance of alpha-granule fibrinogen within the lumen of the surface connected canalicular system. In addition, at 22 degrees C plasmin at doses insufficient to induce platelet aggregation potentiated platelet response to thrombin. Thus, we suggest that plasmin may initiate both activating and inhibitory processes within platelets and that the change of temperature could influence this balance. These results may be of clinical relevance, because the fibrinolytic system was found activated during cardiopulmonary bypass in which the temperature of patient's blood circulation was reduced. This temperature-dependent behavior is also an interesting model for a further study on platelet response to serine proteinases.

Antibodies, Monoclonal↗
PubMed1991

Differential redistribution of platelet glycoproteins Ib and IIb-IIIa after plasmin stimulation.

The subcellular localization of the platelet membrane receptors glycoproteins (GP) Ib and IIb/IIIa [corrected] has been studied within resting platelets by a combination of biochemical and cytochemical techniques. While both GPIb and GPIIb/IIIa are localized within the plasma membrane and surface-connected canalicular system (SCCS) membranes, only GPIIb/IIIa is present within the internal face of alpha-granular membranes. Previous studies demonstrated that plasmin can induce platelet stimulation and also decrease ristocetin-induced platelet aggregation; it was suggested that this was because of GPIb degradation by plasmin. In this study, the respective localizations of both GPIb and GPIIb/IIIa were visualized during in vitro plasmin stimulation of platelets. Generally, plasmin induced shape change, pseudopod formation, organelle centralization either with or without alpha-granule release depending on the conditions of stimulation. Plasmin treatment of platelets at 37 degrees C resulted in the disappearance of GPIb from the cell surface and its subsequent redistribution into the channels and vesicles of the SCCS with no significant modification of GPIIb/IIIa remaining on the plasma membrane. Within degranulated platelets, GPIIb/IIIa was expressed on the plasma membrane and within membranes of large vacuoles containing the alpha-granule proteins. GPIb was virtually absent from these structures and mainly restricted to the SCCS. Addition of cytochalasin D inhibited the migration of GPIb to the SCCS. Biochemical measurements confirmed that no important hydrolysis of GPIb had occurred because only very little amounts of glycocalicin were generated during the reaction. In conclusion, in plasmin-treated platelets GPIIb/IIIa is externalized to the plasma membrane while GPIb is internalized into the SCCS. Although previous studies have suggested that plasmin degrades GPIb, the reduction in ristocetin-induced aggregation may be explained by its apparent redistribution within the membranes of the SCCS.

Blood Platelets↗
PubMed1991

Role of active center and lysine binding sites of plasmin in plasmin-induced platelet activation and disaggregation.

Previous studies have shown that plasmin can activate platelets and can also disperse platelet aggregates by degradation of fibrinogen bound to platelets. In this study, the role of the active center and the lysine binding sites (LBS) of human plasmin in activating platelets and in dispersing platelet aggregates is investigated using aprotinin and the tripeptide Val-Phe-Lys-CH2Cl to inhibit the active center and using epsilon-aminocaproic acid (EACA) to specifically block the LBS. Our results show that the catalytic activity of plasmin is indispensable both for activating platelets and for dispersing platelet aggregates. Binding of plasmin to platelets through the LBS enhances its activating potential, since both EACA (1 mM) and Lys-plasminogen (molar ratio of plasminogen:plasmin at 2:1 to 4:1) inhibit plasmin-induced platelet activation, whereas Glu-plasminogen at a molar ratio of 15:1 had no effect. Furthermore, plasmin which lacks the LBS (miniplasmin), is about 3 fold less effective in activating platelets. However, plasmin binding through the LBS is not absolutely required to disperse platelet aggregates, since EACA at 30 mmol/l was unable to prevent disaggregation by plasmin (half disaggregation time: 40 min in the presence of EACA against 27 min in its absence). It also appeared that fibrinogen receptors on activated platelets are resistant to plasmin degradation, and that disaggregation of plasmin-induced platelet aggregates was much slower than the degradation of fibrinogen by plasmin.

Amino Acid Sequence↗
PubMed1991

Effect of dibenzo[a,c]cyclooctene lignans isolated from Fructus schizandrae on lipid peroxidation and anti-oxidative enzyme activity.

The effect of nine dibenzo[a,c]cyclooctene lignans isolated from Fructus schizandrae on in vitro and in vivo lipid peroxidation of liver microsomes as well as on anti-oxidative enzyme activities were studied. Seven of the nine lignans (1 mM) were shown to inhibit Vit C/NADPH induced lipid peroxidation (malondialdehyde (MDA) formation) of rat liver microsomes. Of these compounds, schisanhenol (Sal), S(-)schizandrin C (S(-)sin C) and S(-)schizandrin B (S(-)sin B) were shown to be more potent than Vit E at the same concentration. Sal and Sin B were able to inhibit gossypol-induced superoxide anion generation in rat liver microsomes. In addition, oral administration of Sal and Sin B markedly reduced liver MDA formation induced by ethanol, 15 ml/kg in mice, and increased superoxide dismutase and catalase activities in rat liver cytosol. The data of this paper are in favor of the conclusion that some lignans, like Sal, have strong anti-oxidant activity. The mechanisms of anti-oxidant activity of the lignans were discussed.

Animals↗
PubMed1991

Intrathoracic skeletal muscle ventricles: a feasibility study.

For skeletal muscle ventricles (SMVs) to be applied clinically, it is likely that they will have to be placed within the chest. Ease of subsequent connection to the circulation, and avoidance of significant lung compression, are factors that could influence SMV size and shape in a way that may prejudice their ability to pump effectively at physiological preloads. In five dogs, specially designed SMVs were constructed from the latissimus dorsi muscle, and placed in the apex of the left hemithorax. After a 3-week delay, the muscle was preconditioned electrically by 2-Hz continuous stimulation for 6 weeks. At a later thoracotomy, this positioning of SMVs permitted easy surgical access to the heart and great vessels. SMVs were then connected to a mock circulation device for functional evaluation. As right-sided pumps, at a preload of 10 mmHg, SMVs generated a stroke volume (SV) and stroke work (SW) exceeding that of the native right ventricle (SV = 8.9 +/- 0.8 vs 7.9 +/- 0.6 mL; SW = 0.44 +/- 0.03 vs 0.20 ergs x 10(6)). As left-sided pumps, also at a preload of 10 mmHg, SMV SV, and SW was roughly half that of the left ventricle (SV = 3.7 +/- 0.2 vs 7.9 +/- 0.6 mL; SW = 0.29 +/- 0.03 vs 0.57 +/- 0.05 ergs x 10(6)). SMVs may conveniently be positioned inside the chest, where they have the potential to function as left or right heart assist devices.

Animals↗
PubMed1991

Canine latissimus dorsi cardio-double myoplasty: acute feasibility study.

Cardio-double myoplasty was performed in eight mongrel dogs. Both latissimus dorsi muscles were dissected from the chest wall and wrapped around the heart. They were then stimulated using an R wave synchronous stimulator. Hemodynamic measurements were obtained, first with the stimulator off and then with stimulator activated. After measuring hemodynamic effects in a normal heart, acute heart failure was induced by the infusion of propranolol (5 mg/kg). Hemodynamic data were then obtained in the same fashion. In a normal heart state, cardio-double myoplasty increased the cardiac output 9.9% +/- 2.24 (p less than 0.005), the left ventricular pressure 18.7% +/- 3.53 (p less than 0.001), the pulmonary artery pressure 72.2% +/- 25.4 (p less than 0.01), and the stroke volume 13.4% +/- 5.73 (p less than 0.05). In a failing heart, the cardiac output increased 21.6% +/- 3.34 (p less than 0.005), the left ventricular pressure increased 20.8% +/- 3.34 (p less than 0.005), the pulmonary artery pressure increased 87.2% +/- 39.9 (p less than 0.05), and the stroke volume increased 46.9% +/- 22.9 (p less than 0.05). The left ventricular end-diastolic pressure decreased slightly and the central venous pressure did not change in either the normal state or during cardiac failure. Cardio-double myoplasty resulted in a significant circulatory augmentation particularly in the setting of cardiac failure.

Animals↗
PubMed1991

Chemical synthesis, cloning and expression of human epidermal growth factor gene in Saccharomyces cerevisiae.

A gene coding for human epidermal growth factor (hEGF) has been chemically synthesized by solid-phase phosphoramidite method. The 173 base-pair synthetic DNA duplex consists of a structural gene encoding hEGF, a stop codon TGA at 3' end and some convenient restriction sites at both ends of the gene. The synthesis of the gene involved enzymatic joining of 8 oligonucleotides to form a DNA duplex which was cloned into vector M13mp18. The recombinant colonies were identified by dot hybridization and restriction enzyme digestion. Its accuracy was confirmed by DNA sequence analysis. The hEGF DNA was inserted into yeast secretory vector YFD59. The resulting expression plasmid YFD104 was introduced into yeast Saccharomyces cerevisiae. The binding assay showed that the yeast transformants could express and secrete hEGF.

Amino Acid Sequence↗
PubMed1991

[Combined pharmacokinetic-pharmacodynamic model of procainamide in rabbits with induced ventricular fibrillation threshold (VFT) changes].

The change of electrically induced VFT was chosen as index of effect in anesthetized rabbits for study of pharmacodynamics of PA and NAPA. We analyzed the pharmacokinetic properties of PA and NAPA and elucidated their effect kinetics with a pharmacokinetic-pharmacodynamic (PK/PD) model in view of different transfer qualities. A linear-addition effect model was used to describe the relationship between the effect and the amount of drug and its metabolite in the effect compartment. PA was found to be eliminated faster than NAPA and distributed more extensively in rabbits. The effect per unit concentration of PA was shown to be larger than that of NAPA.

Acecainide↗
PubMed1991

[Incidence of venous air embolism in parturients during cesarean section with regional anesthesia].

The purpose of the study is to probe the situation of venous air embolism (VAE) and the accompanying complications occurring in Chinese parturients in Taiwan during Cesarean section. Sixty ASA physical status class I-II parturients who were subjected to cesarean section under regional anesthesia were evaluated. The sensor of the Doppler device was placed on the anterior chest to detect the rumbles of air when it came to pass, and simultaneously the signs and symptoms following VAE were observed. Our results demonstrated that the usual or normal Doppler heart sound changed in 38 parturients out of 60 (63.3%), and the alteration occurred very often when the uterus was being incised (81.6%), or sutured (97.4%), and concurred strong correlation with such signs and symptoms such as chest tightness or precordial pain (78.9%), shortness of breath (60.5%), and change of heart rate or blood pressure (86.8%). The method of anesthesia (spinal or epidural block) did not have effect on the occurrence of VAE, but different surgical approaches and different positions in which the patients were posed during operation did apparently bring about VAE of variable degree. Besides, supplying of oxygen could mitigate the symptoms produced by VAE. Consequently, the application of Doppler monitor during Cesarean section can detect VAE earlier and more efficiently and thus provides information timely treatment.

Anesthesia, Epidural↗
PubMed1991

Dysfibrinogenemia and thrombosis.

A thrombotic tendency (venous or arterial) has been reported in some cases of dysfibrinogenemia. We report here the mechanism by which these thrombosis may occur. It may be related either to a defective clot lysis due to a poor reactivity toward fibrinolytic enzymes or to a defective thrombin binding capacity of the abnormal clot. Acquired fibrin clot structure anomalies may also be responsible for a defective thrombolysis.

Fibrin↗
PubMed1990

KRDS, a new peptide derived from human lactotransferrin, inhibits platelet aggregation and release reaction.

KRDS (Lys-Arg-Asp-Ser), a tetrapeptide from human lactotransferrin, was tested in vitro on human platelet function, and its effects were compared to those of RGDS, a tetrapeptide from human fibrinogen. Both peptides had a high probability of initiating a beta-turn and were highly hydrophilic. KRDS inhibited ADP-induced platelet aggregation [median inhibitory concentration (IC50) 350 microM] and fibrinogen binding (IC50 360 microM) to a lesser extent than RGDS (IC50 75 microM and 20 microM, respectively). Different from RGDS, thrombin-induced serotonin release was inhibited by KRDS (750 microM) on normal platelets (55 +/- 10%) and type I Glanzmann's thrombasthenia platelets (43% +/- 1). However, KRDS had no effect on cytoplasmic Ca2+ mobilization, inositol phospholipid metabolism or protein phosphorylation (myosin light chain P20 and P43). In contrast to RGDS, KRDS does not inhibit the binding of monoclonal antibody PAC-1 to activated platelets. KRDS and RGDS inhibited 4 beta-phorbol-12-myristate-13-acetate (PMA)-induced aggregation and fibrinogen binding, while proteins were normally phosphorylated. Thus, the tetrapeptide KRDS is (a) an inhibitor of serotonin release by a mechanism independent of protein phosphorylation and (b) an inhibitor of fibrinogen binding and, hence, aggregation by a mechanism that may not necessarily involve its direct binding to the glycoprotein IIb-IIIa-complex.

Adenosine Diphosphate↗
PubMed1990

1-Butyryl-glycerol: a novel angiogenesis factor secreted by differentiating adipocytes.

Differentiation of adipocytes is accompanied by secretion of molecules stimulating angiogenesis in vivo and endothelial cell growth and motility in vitro. We demonstrate that the angiogenic and motility-stimulating activities secreted by adipocytes are separable from the endothelial cell mitogenic activity by fractionation of adipocyte-conditioned medium. The major differentiation-dependent angiogenic molecule was purified and identified by GCMS as 1-butyryl-glycerol (monobutyrin). Monobutyrin levels increase at least 200-fold during adipocyte differentiation and represent a major fraction of the total angiogenic activity. Synthetic monobutyrin shows the same spectrum of biological activities as the adipocyte-derived factor: stimulation of angiogenesis in vivo and microvascular endothelial cell motility in vitro, with no effect on endothelial cell proliferation. Angiogenesis is stimulated at doses as low as 20 pg when tested in the chick chorioallantoic membrane assay. These results strongly suggest that monobutyrin is a key regulatory molecule in an angiogenic process linked to normal cellular and tissue development.

Adipose Tissue↗
PubMed1990

Chloroquine's modulation of endothelial cell activity induced with basic fibroblast growth factor and human serum: effect on mitogenesis, protease production and cell migration.

Chloroquine modulates the activity of cultured human microvascular endothelial (HOME) cells in a complex fashion. At concentrations of 5-25 microM, CQ inhibits basic fibroblast growth factor (bFGF-) and human serum-induced mitogenic activity in these cells, in a dose-dependent manner. The kinetics of CQ's inhibitory actions on serum-induced mitogenesis in HOME cells slowly develops with only 30% of maximum inhibition reached after 24 hours. In HOME cells grown in serum-free medium, CQ raised tissue-plasminogen activator antigen levels in cell extracts. There was also a potentiation of bFGF-induced t-PA production. The kinetics of CQ's stimulatory effect on t-PA production by HOME cells, suggest that this effect precedes its inhibitory actions on mitogenesis. This effect of CQ on t-PA generation in endothelial cells was susceptible to cycloheximide inhibition. In wound assays, HOME cell migration, induced with bFGF and HS, was potentiated by CQ.

Blood Proteins↗
PubMed1990

Enhancement of human herpesvirus 6 replication in adult human lymphocytes by monoclonal antibody to CD3.

The effect of monoclonal antibody to CD3 on human herpesvirus 6 (HHV-6) replication was assessed in adult peripheral blood mononuclear cells (PBMC) and in cord blood mononuclear cells (CBMC) by anticomplement immunofluorescence and Southern blot hybridization. Infection of CBMC by HHV-6 was productive; however, little or no infection was observed with PBMC from adults exposed to the virus even if stimulated by phytohemagglutinin. Monoclonal antibody to CD3 strongly enhanced HHV-6 replicative cycles in PBMC from adults.

Antibodies, Monoclonal↗
PubMed1990

Interferon induction by human herpesvirus 6 in human mononuclear cells.

Interferon (IFN) production after inoculation with human herpesvirus 6 (HHV-6) was studied in peripheral blood mononuclear cells from 10 HHV-6-seropositive healthy adults and five samples of cord blood mononuclear cells. When the cells were exposed to HHV-6 at a multiplicity of infection of 10(-2) 50% tissue culture infectious doses/cell, IFN activity was detected as early as 12 h after exposure to HHV-6, plateaued at days 2-5, and gradually decreased thereafter. IFN was also induced by ultraviolet-inactivated but not heat-inactivated HHV-6. The response of cord blood mononuclear cells was lower than that of the cells from healthy adults. The activity of all IFN samples was stable to acid and exclusively neutralized by anti-human IFN-alpha. The IFN-producing cell population was mainly non-T cells and monocytes. Furthermore, exogenous IFN suppressed HHV-6 replication. Production of IFN-alpha may be an important part of the host response to HHV-6.

Cell Separation↗