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Biomedical subjects

Z Y Lu

Publications and source records attributed to Z Y Lu.

At least 55 records · Page 3Linked to original sources

Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma.

We report a novel, reproducible methodology which enabled 10 human myeloma cell lines (HMCL) to be obtained from each of 10 tumor samples harvested from 9 patients with extramedullary proliferation. Fresh samples were cultured with interleukin 6 (IL-6) and granulocyte macrophage-colony stimulating factor (GM-CSF) at a high cell density and resulting HMCL growth became progressively dependent on IL-6 alone, no longer requiring GM-CSF. These HMCL, which had the same immunoglobulin gene rearrangements as the patients' original myeloma cells, were designated XG-1 to XG-9. XG HMCL had a plasma cell morphology, expressed plasma cell antigen (Ag), namely cytoplasmic immunoglobulins, CD38, B-B4 Ag, and CD77, and lacked the usual B-cell Ag. They also expressed activation antigens such as CD28 with coexpression of CD28 and its ligand, B7 Ag, in four HMCL. Six HMCL expressed CD40, 4 CD23, and 5 its ligand, CD21. The XG HMCL bore adhesion molecules VLA-4 and CD44 (all 10 HMCL), VLA-5 (7 HMCL), and CD56 (4 HMCL). Finally, cytogenetic study of 8 HMCL indicated a 14q+ chromosome, and t(11,14) translocation was found in 6 of 8 and 5 of 8 HMCL, respectively. The possibility of obtaining malignant plasma cell lines reproducibly from each patient with extramedullary proliferation offers a unique tool for studying the phenotype and abnormalities of the still unidentified tumor stem cell in this disease.

Cell Division↗

Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and oncostatin M are growth factors for human myeloma cell lines using the interleukin 6 signal transducer gp130.

Interleukin 6 (IL-6) is a major growth factor for tumor plasma cells involved in human multiple myeloma (MM). In particular, human myeloma cell lines (HMCL), whose growth is completely dependent on addition of exogenous IL-6, can be obtained reproducibly from every patient with terminal disease. Four cytokines, ciliary neurotropic factor (CNTF), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OM), use the same transducer chain (signal transducer gp130) as IL-6 and share numerous biological activities with this IL. We found that these four cytokines stimulated proliferation and supported the long-term growth of two out of four IL-6-dependent HMCL obtained in our laboratory. Half-maximal proliferation was obtained with cytokine concentrations ranging from 0.4 to 1.2 ng/ml for IL-11, LIF, and OM. CNTF worked at high concentrations only (90 ng/ml), but addition of soluble CNTF receptor increased sensitivity to CNTF 30-fold. The growth-promoting effect of these four cytokines was abrogated by anti-gp130 antibodies, contrary to results for anti-IL-6 receptor or anti-IL-6 antibodies. No detectable changes in the morphology and phenotype were found when myeloma cells were cultured with one of these four cytokines instead of IL-6. Concordant with their IL-6-dependent growth, the four HMCL expressed membrane IL-6R and gp130 detected by FACS analysis. LIF-binding chain gene (LIFR) was expressed only in the two HMCL responsive to LIF and OM.

Antigens, CD↗

gamma-Interferon in multiple myeloma: inhibition of interleukin-6 (IL-6)-dependent myeloma cell growth and downregulation of IL-6-receptor expression in vitro.

In multiple myeloma, malignant plasma cells from most patients with active disease proliferate spontaneously when cultured for 5 days in vitro. This spontaneous proliferation is related to the endogenous production of interleukin-6 (IL-6), the major myeloma-cell growth factor. A 50% inhibitory dose (100 U/mL) of human recombinant gamma-interferon (hr gamma-IFN) blocked the proliferation of myeloma cells almost completely in all 19 patients analyzed. This inhibition was not caused by suppression of endogenous IL-6 production and was also observed in the presence of an excess of hrIL-6. hr gamma-IFN was also completely inhibitory in four human myeloma cell lines (HMCL) whose growth is totally dependent on the addition of exogenous hrIL-6. This inhibition was associated with a 47% to 73% decrease in membrane IL-6-binding gp80 protein as well as with a 90% decrease in the amount of gp80 mRNA in HMCL. These results are in line with recent reports indicating that gamma-IFN inhibited several IL-6-dependent biologic processes. They suggest a need to reconsider why previous preliminary clinical trials failed to demonstrate a beneficial effect of gamma-IFN in multiple myeloma.

Bone Marrow↗

Evaluation of exercise-induced QRS amplitude changes (Athens score) and their clinical value.

The index of exercises-induced amplitude changes in a combination of Q, R and S waves, named Athens score, was tested in 213 patients, who underwent coronary angiography within 3 days of a maximal exercise test. Of the 155 cases with conclusive exercise test results, according to the coronary angiography document, 23 (14.8%) were diagnosed as having no significant coronary artery disease (CAD); 27 (17.4%) as 1-vessel disease; 28 (18.1%) as 2-vessel disease and 77 (49.7%) as 3-vessel disease. The Athens score for them was 4.87 +/- 2.89, 0.02 +/- 3.35, -1.70 +/- 3.68, -1.75 +/- 3.98 respectively, F = 19.65, P < 0.01. An Athens score of 2 mm predicted CAD with sensitivity of 84.9% and specificity of 78.3% both being higher than those of ST segment depression (75.0% and 60.9%). It was concluded that the Athens score was a promising index for improving the efficiency of exercise test to predict CAD.

Adult↗

Overall interleukin-6 production exceeds 7 mg/day in multiple myeloma complicated by sepsis.

We previously reported that injection of anti-IL-6 monoclonal antibody (mAb) in a patient with multiple myeloma (MM) induced the circulation of high amounts of IL-6 in the form of IL-6/anti-IL-6 monomeric complexes. This made it possible to estimate overall daily IL-6 production in patients in vivo, which had not been achieved in animals or humans before. In this study, estimations are given for a patient with MM who developed Escherichia coli sepsis during anti-IL-6 mAb. During the first 12 days, the overall IL-6 production was estimated at 1.5 to 2.0 micrograms/day. On day 13, serum IL-6 concentration, in the form of IL-6/anti-IL-6 complexes, increased 1000-fold and was 1.7 x 10(6) pg/ml, in relation with the development of E. coli sepsis. Overall IL-6 production was estimated to be greater than 7 mg/day, i.e. 3500 times higher than before sepsis. Serum IL-6 levels in the form of monomeric immune complexes remained very high for 20 days after sepsis indicating the persistence of very high overall IL-6 production (100 to 3500-fold greater than pre-sepsis production). This study demonstrates a considerable and persistent potential for IL-6 production in this patient during and after sepsis.

Antibodies, Monoclonal↗

High amounts of circulating interleukin (IL)-6 in the form of monomeric immune complexes during anti-IL-6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo.

A patient with plasma cell leukemia was treated with anti-interleukin (IL)-6 monoclonal antibodies (mAb) for 2 months. Using chromatography on protein A-Sepharose, anti-murine-IgG-Sepharose, anti-IL-6-mAb-Sepharose and gel filtration at pH 2.3, we have demonstrated that the anti-IL-6 mAb, by preventing the binding of IL-6 to its cell membrane receptor and its renal elimination, has induced huge amounts of IL-6 to circulate in the form of monomeric immune complexes. By using this observation, we have developed a mathematical modelling that allows the determination of the overall daily production of IL-6 in this patient, which was in the range of 15 micrograms per day. Overall in vivo production of cytokines has never been evaluated in animals or in humans before.

Antibodies, Monoclonal↗

Comparison between laser and electrical ablation of ventricle in dogs: hemodynamic, pathologic and electrocardiographic observations.

To characterize and compare the pathologic, hemodynamic and electrocardiographic changes of both transcatheter laser and electrical energy on ventricle, 36 subendocardial myocardium lesions were induced at energy 60, 120 and 240 Joules by either transcatheter laser irradiation or electrical shock in 7 anesthetized dogs. The following results were observed: 1) Both laser and electrical ablation on myocardium created nonhomogeneous myocardium injury, but laser ablation caused mainly focal tissue vaporization and necrosis, while electrical shock induced widespread tissue degenerations; 2) Both laser and electrical induced-lesion dimensions increased parallel to the total dosage of energy; 3) Laser ablation caused mainly (90%) single ventricular premature beats and 86% of them occurred within the first minute after energy discharged, while ventricular tachycardias were found in any electrical energy groups; ventricular fibrillations occurring during laser and electrical ablation were 5% and 13% respectively (P < 0.01); 4) A decrease in aortic blood pressure and an increase in central venous pressure induced by laser ablation were significantly less than that produced by the same amount of electrical energy (P < 0.01). Our preliminary results have shown that transcatheter laser ablation has great potential for becoming a practical method in the management of refractory tachycardias.

Animals↗

Association of vanadate-sensitive Mg(2+)-ATPase and shape change in intact red blood cells.

Intact human erythrocytes, initially depleted of Mg2+ by EDTA incubation in the presence of A23187, exhibit Mg(2+)-dependent phosphate production of around 1.5 mmol per liter cells.h, half-maximally activated at around 0.4 mM added free Mg2+. This appears to correspond to Mg(2+)-stimulated adenosine triphosphatase (Mg(2+)-ATPase) activity found in isolated membranes, which is known to have a similar activity and affinity for Mg2+. Vanadate (up to 100 microM) inhibited Mg(2+)-dependent phosphate production and ATP breakdown in intact cells. Over a similar concentration range vanadate (3-100 microM) transformed intact cells from normal discocytes to echinocytes within 4-8 h at 37 degrees C, and more rapidly in Mg(2+)-depleted cells. The rate of Ca(2+)-induced echinocytosis was also enhanced in Mg(2+)-depleted cells. These results support previous studies in erythrocyte ghosts suggesting that vanadate-induced shape change is associated with inhibition of Mg(2+)-ATPase activity localized in the plasma membrane of the red blood cell.

Adenosine Triphosphate↗

[Synthesis and analgesic activity of analogs of 4-methoxymethyl fentanyl].

In this paper, the synthesis and analgesic activities of some derivatives of N-[1-(2-phenylethyl)-4-methoxymethyl-4-piperidinyl]-N-propionylanilin e (4-methoxymethyl fentanyl) are reported. In mouse hot plate test, most compounds in this series showed strong narcotic analgesic activities but their activities were lower than those of compounds in the series of 4-methoxycarbonyl fentanyl.

Analgesics, Opioid↗

Ethnic differences in physiological responses associated with the Valsalva maneuver.

Ethnic differences in cardiovascular indices at rest and across the Valsalva maneuver (VM) were studied in 30 Asian, 86 Caucasian, and 12 Black healthy men and women aged 30 to 55 years. Subjects simulated the VM by blowing into an aneroid pressure-gauge meter to 40 mmHg for 10 seconds. Resting systolic blood pressure (SBP) was significantly higher in Blacks than in Asians or Caucasians. During the strain phase of the VM, the fall in SBP from baseline was significantly greater in Asians and Blacks than in Caucasians. Further, Asians had the greatest overshoot of SBP above baseline. Although resting heart rate was significantly higher in Asians compared to Caucasians, there were no differences in heart rate responses to the VM. Reduction in carotid artery blood flow velocity during strain was significantly less in Blacks. We conclude that there are ethnic differences in cardiovascular indices at rest and across the VM.

Adult↗

[Detection of circulating antigen in schistosomiasis by dot-ELISA with monoclonal antibody].

Circulating antigen in sera from acute, chronic and late stages of schistosomiasis patients was detected by direct dot-ELISA with monoclonal antibody 3D8A against schistosome gut-associated cathodic antigen linked with peroxidase, the positive rates being 90.6%, 83.2% and 30.7%, respectively. No positive reactions were found with sera from patients of clonorchiasis, malaria and non-parasitic diseases. The positive rate and the circulating antigen level in EPG greater than 100 group of patients were found to be higher than those in EPG less than 100 group. Circulating antigen became negative one year after praziquantel treatment in 84.0% of patients who showed negative fecal examination, while the other patients remained positive with decreasing titers. The results indicated that the circulating antigen in sera from schistosomiasis patients of various stages can be detected by dot-ELISA with monoclonal antibody 3D8A against circulating schistosome gut-associated cathodic antigen. The authors concluded that the circulating antigen level was correlated with the intensity of infection and the efficacy of treatment.

Animals↗

Antiviral effect of mangiferin and isomangiferin on herpes simplex virus.

Using tissue culture technique the present study for the first time indicated the antiviral effect of mangiferin and isomangiferin against type I herpes simplex virus (HSV-I). 4 methods were used for evaluating drug effectiveness (i.e., in vitro drug-on-virus direct action, simultaneous addition of drug-virus-inoculum to cell bottle, virus inoculation preceding drug addition, and drug addition followed by virus inoculation), it was readily found by log determination of HSV-I inhibition that isomangiferin somewhat exceeded such control drugs as acyclovir, idoxuridine, and cyclocytidine in log by 0.27-0.50, and that mangiferin was lower than isomangiferin in log by 0.53. The average plaque reduction rates of mangiferin and isomangiferin were 56.8% and 69.5% respectively. The antiviral effect of mangiferin and isomangiferin was presumably due to their capability of inhibiting virus replication within cells.

Antiviral Agents↗

[Synthesis and analgesic activity of 4-N-propionyl analogs of 4-methoxycarbonyl fentanyl].

In the present paper, the synthesis and analgesic activities of some 4-N-propionyl analogs of 4-methoxycarbonyl fentanyl are reported. In mouse hot plate test, most of these compounds showed strong narcotic analgesic activity. The analgesic activities of compounds 1379, 1385 and 1387 were found to be more potent than that of 4-methoxycarbonyl fentanyl.

Analgesics↗

Periodontal conditions in 35-44-year-old factory workers in Shanghai.

A periodontal survey applying CPITN was carried out in almost 500 male and female factory workers, 35-44 yr of age, in Shanghai, P.R. China. Calculus and shallow pockets were most frequent. Deep pockets of 6 mm and over were seldom found. The mean number of missing teeth was only 2.7 (out of 32). Problems associated with third molars seem to provide the largest immediate oral health problem.

Adult↗

A study of magnetic field in the lung of workers in an asbestos factory.

Magnetic field at the chest in 93 male workers exposed to asbestos dust in an asbestos products factory in China was studied by local magnetization and flux-gate gradiometry. The average field intensity at 12 measurement points over the anterior chest wall was compared among workers with and without asbestosis and among workers of different working age. The field intensity in workers with asbestosis and those suspected to have asbestosis on the basis of X-ray findings was significantly higher than that in workers without asbestosis. It was also found that the field intensity increased with working age. It is suggested that dynamic measurement of magnetic field in the lung of workers exposed to dust containing ferrimagnetic particles would at least serve as a quantitative method for estimating lung dust loads and be valuable for pneumoconiosis prevention.

Asbestosis↗

[Antiviral effect of mangiferin and isomangiferin on herpes simplex virus].

Using tissue culture techniques the present study assured us of the merits of mangiferin and isomangiferin in the antiviral action against HSV-1. Utilizing 4 main patterns for evaluating drug effectiveness (ie intratube drug-on-virus direct action, simultaneous addition of drug-virus-inoculum to cell bottle, virus inoculation preceding drug addition, and drug addition followed by virus inoculation), it was readily found by logarithm determination of HSV-I inhibition that isomangiferin was superior to such control drugs as acyclovir, idoxuridine, and cyclocytidine in logarithm by 0.27-0.50, and that mangiferin was lower than isomangiferin in logarithm by 0.53. The average plaque reduction rates of mangiferin and isomangiferin were 69.5% and 56.8%, respectively. All in all, the antiviral effect of mangiferin and isomangiferin was attributed presumably to their capability to inhibit virus replication within cells.

Antiviral Agents↗