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Biomedical subjects

S Lu

Publications and source records attributed to S Lu.

At least 145 records · Page 8Linked to original sources

Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group.

The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone.

Acetates↗

Molecular mechanisms of androgen-independent growth of human prostate cancer LNCaP-AI cells.

The goal of this study is to investigate the molecular mechanisms of androgen-independent growth in prostate cancer. We have established an androgen-independent prostatic carcinoma LNCaP-AI (defined as a LNCaP cell line that is capable of growing in charcoal-stripped serum) from the androgen-dependent LNCaP-FGC cells. In contrast to the androgen-independent PC-3 human prostate cancer cells, LNCaP-AI cells still express a similar level of androgen receptor as their parental cells and are sensitive to androgen stimulation. Compared with the parental LNCaP-FGC cells, LNCaP-AI cells are more resistant to apoptosis induced by 12-O-tetradecanoylphorbol-13-acetate and express a much higher level of antiapoptotic gene bcl-2 and cyclin-dependent kinase inhibitor p21, which may confer an enhanced antiapoptosis phenotype. On the other hand, expression of cyclin-dependent kinase inhibitor p16 is significantly reduced in the LNCaP-AI cells, implying the release of an inhibitory effect of p16 on cell cycle progression. Taken together, our results suggest that multiple factors contribute to the development of androgen-independent growth of prostatic carcinoma cells, including enhancement of cell antiapoptosis function, release of cell cycle inhibition, and stimulation of cell proliferation by alternative signaling pathways.

Androgens↗

Thyrotropin prevents apoptosis by promoting cell adhesion and cell cycle progression in FRTL-5 cells.

Apoptosis has been shown to be involved in endocrine tissue homeostasis as well as regression due to hormone deprivation. The goal of this study was to induce apoptosis and to investigate a potential role of TSH as a survival factor in thyroid follicular cells (FRTL-5) in vitro. Our results indicated that FRTL-5 cells underwent anchorage-dependent apoptosis when plated in the absence of serum and hormones, but when the cells became attached to the substrate by addition of TSH in the medium, apoptosis was prevented. The apoptosis was evaluated by positive terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling staining, typical apoptotic bodies by electron microscopy, DNA ladder by gel electrophoresis, and subdiploidy by propidium iodide-stained flow cytometry. TSH was shown to prevent apoptosis and maintain cell viability. cAMP partly mimicked this effect, which was inhibited by a specific inhibitor of protein kinase A, H-89. While investigating the mechanisms of apoptosis, we observed that the phosphorylated focal adhesion kinase was strengthened by TSH. Furthermore, FRTL-5 cells were found to undergo growth arrest in the G1 phase in the absence of TSH, accompanied by an elevated level of cyclin-dependent kinase inhibitor, p27, and a decreased level of cyclin D. In contrast, TSH promoted transition from G1 to S phase by decreasing P27 protein and increasing cyclin D expression. We concluded that in addition to regulating growth and differentiation, TSH may function as a survival factor in thyroid cells by preventing anchorage-dependent apoptosis in FRTL-5 cells partly via the cAMP pathway.

Animals↗

Androgen regulation of the cyclin-dependent kinase inhibitor p21 gene through an androgen response element in the proximal promoter.

Androgen is essential for the physiological maintenance of the integrity of prostatic epithelial cells, and castration causes the cells to undergo apoptosis. To study the molecular mechanism of androgen-dependent cell growth, we showed that androgen up-regulates the expression of the cyclin-dependent kinase inhibitor p21 (WAF1, CIP1, SDI1, CAP20) gene at both the mRNA and protein levels. Nuclear run-on assays demonstrated that androgen stimulates endogenous p21 gene expression at the transcriptional level. Transient transfection experiments showed that androgen can enhance the activity of a 2.4-kb promoter of the p21 gene linked to a luciferase reporter. These results suggested that a putative androgen response element (ARE), which mediates androgen response to enhance the p21 transcription, is included in the 2.4-kb promoter fragment. Deletion analysis of the promoter revealed a functional ARE (AGCACGCGAGGTTCC) located at -200 bp of the p21 gene proximal to the promoter region. Electrophoretic mobility shift assay further demonstrated that the androgen receptor specifically binds to this element. Wild-type ARE, but not mutant ARE, confers androgen responsiveness to a heterologous promoter. The up-regulation of p21 gene expression by androgen suggests that p21 may have an antiapoptotic function in prostatic epithelial cells. However, this hypothesis will need to be tested in future experiments.

Androgens↗

Correlation of duplex sonography findings and portal pressure in 375 patients with portal hypertension.

OBJECTIVE: The purpose of this study was to determine the potential usefulness of duplex sonography in the grading of portal hypertension. SUBJECTS AND METHODS: Duplex sonography of the portal vein system and measurement of the portal pressure and portosystemic pressure gradient were performed in 375 patients before placement of transjugular intrahepatic portosystemic shunts. Subgroups included patients with recent variceal bleeding (n = 296) and patients with refractory ascites without previous variceal bleeding (n = 79). A matched cohort of 100 patients without portal hypertension was also examined. Differences between the groups in portal and splenic vein diameter, flow velocity, congestion index, and hepatic arterial resistive index were assessed using the Wilcoxon rank sum test. RESULTS: Compared with healthy individuals, our patients had an increased portal vein diameter (+30%, p < .001), decreased portal vein flow velocity (-44%, p < .001), and increased congestion index (+185%, p < .001). A portal vein diameter greater than 1.25 cm or a portal vein flow velocity less than 21 cm/sec indicated portal hypertension with a sensitivity and specificity of 80%. If the congestion index exceeded 0.1, portal hypertension was diagnosed with a 95% sensitivity and specificity. The portal pressure and gradient correlated only weakly (r < .2, p < .05) with sonographic variables. Using multivariate analysis, subgroups with variceal bleeding or refractory ascites did not show differences in hemodynamics, including pressures. CONCLUSION: Duplex sonography contributes to the diagnosis of portal hypertension but does not allow its grading. Similarity of portal hemodynamics between patients with variceal bleeding and patients with refractory ascites suggests that additional factors determine the respective clinical presentation.

Female↗

[Specific immune responses in H-2d mice after DNA immunization of HBV core gene].

OBJECTIVE: To observe the specific immune responses in H-2d mice after DNA immunization of HBV core gene. METHODS: The DNA vaccine (pJW4303/HBc) was constructed by inserting HBV core gene fragment into the reading frame of plasmid pJW4303. Both methods of gene gun and intramuscular immunization were used in this experiment. Anti-HBc (IgG) and its isotypes (IgG1, IgG2a) in mice sera were detected by ELISA. HBcAg specific cytotoxic T lymphocyte (CTL) activity was measured by 51Cr release assay. RESULTS: The expression of HBcAg was confirmed by ELISA and Western-blot in 293T cells transfected with pJW4303/HBc. The end-point titers of serum anti-HBc in immunized mice were 1: 328,050 (gene gun method) and 1:109,350 (intramuscular method). In both groups of gene gun and intramuscular immunization IgG2a level was slightly higher than IgG1. HBcAg specific CTL activities were 51. 1% in gene gun group and 55.2% in intramuscular group. CONCLUSION: In this experiment the DNA vaccine of pJW4303/HBc shows strong antigenecity in both cellular and humoral immunity.

Animals↗

[Comparative genomic hybridization analysis of primary gastric carcinomas].

OBJECTIVE: To investigate whether unknown genes are involved in the tumorigenesis of gastric cancer. METHODS: Fourty-three primary gastric carcinomas were analyzed by comparative genomic hybridization(CGH). RESULTS: A gain in chromosome 3p(8/43), 8q(8/43), 20[20(9/43), 20p(7/43), 20q(4/43)], 12q (16/43), and 13q(12/43) was observed while a loss of 19[19(15/43), 19p (13/43)], 17[17(8/43), 17p(10/43)], 16(10/43) and 1p(11/43) was discovered. CONCLUSION: There were characteristic changes in 3p, 8q, 20, 12q, 13q, 19, 17, 16, and 1p in gastric carcinoma, and some unknown genes located in the above regions might be of importance to gastric carcinoma pathogenesis.

Chromosome Aberrations↗

Study on pottical type, palmar and plantar digital formulae, hand clasping, arm folding, handedness, leg folding and stride type in the Daur population, China.

The pottical type, palmar and plantar digital formulae, hand clasping, arm folding, handedness, leg folding and stride type have been investigated on a sample of 143 male and 160 female students of the Daur population of Molidawa Banner, Inner Mongolia. The results of this study are the following: 1. the frequency of the hyperextensive pottical type is 49.17%, the relative length of index over annularis 12.21%, right hand clasping 45.87%, right arm folding 49.50%, right handedness 94.39%, right leg folding 72.28% and right stride type 44.88%, 2. pottical type, hand clasping, handedness, leg folding and stride type do not show significant sex differences, 3. there are some relations between hand clasping and arm folding as well as between arm folding and stride type, 4. compared with other population groups, the Daur population shows a low frequency of right hand clasping, a moderate frequency of right arm folding and a low frequency of left handedness.

Adolescent↗

[Down-regulation effect of McAb HIM82 on Ca2+, protein kinase C, protein tyrosine kinase signal pathway of neutrophils].

OBJECTIVES: To study the control effects of HIM82 and HIM70 on reactive oxygen species (ROS) released from respiratory burst of neutrophils (Np), and the action of HIM82 on relevant signal transduction pathway. METHODS: The experimental group (combining with McAb) was compared with the control group with regard to the ROS level, activity of G protein, intracellular [Ca2+] level, the activities of PKC and PTK in activated Np to interpret the mechanism by which the McAb down-regulated the respiratory burst. RESULTS: The positive rate of Np combined with HIM82 was shown over 95% using indirect immunofluorescence assay (control group was 0). The generation of superoxide anion and hydrogen peroxide from PMA-treated Np were decreased by 55% (P < 0.01) and 32% (P < 0.01) with 30 micrograms/ml HIM82. The amount of H2O2 produced in FMLP or SP-stimulated Np were decreased by 16% (P < 0.01) and 37% (P < 0.01) respectively. A similar effect of HIM70 on Np was observed. Furthermore, the inhibition of H2O2 in FMLP-activated Np affected by PT, a specific inhibitor for G-protein, and in HIM82 was 42% and 60% separately, and that with both PT and HIM82 was 85%. It was suggested that HIM82 could enhance the inhibition effect of PT on G-protein. The intracellular [Ca2+] level of Np stimulated with FMLP was decreased by 85%, and that of Np activated with PMA by 100% nearly in the present of HIM82. The activities of PKC and PTK in PMA-stimulated Np were decreased by 23% (P < 0.05) and 35% (P < 0.05) separately when treated with HIM82. CONCLUSION: The McAb HIM82 could down-regulate the ROS produced from activated Np. The mechanism of decreasing ROS may be involved in down-regulating Ca(2+)-PKC and PTK signal transduction pathway activities that are upstream control systems for NADPH oxidase activation.

Antibodies, Monoclonal↗

[Humoral and cellular immunogenecity of genetic vaccine on core gene of hepatitis B virus in mice].

OBJECTIVE: To observe the specific humoral and cellular immunogenecity of genetic vaccine based on core gene of hepatitis B virus in both C57BL/6(H-2b) and BALB/c(H-2d) mice. METHODS: The in vitro expressing product of genetic vaccine of HBV core antigen (HBcAg) was identified by Western-blot. Both methods of gene gun and intramuscular immunization were used. Anti-HBc(IgG) and its isotypes (IgG1, IgG2a) in mice sera were detected by indirect ELISA. HBcAg specific cytotoxic T lymphocyte(CTL) activity was measured by 51Chromium release assay. RESULTS: The expression of HBcAg was confirmed by Western-blot. High titers of serum anti-HBc(1:328,050 by gene gun method and 1:109,350 by intramuscular method) were raised in both H-2b and H-2d mice after immunization with genetic vaccine of HBcAg. The levels of IgG2a isotype were generally higher than those of IgG1 in all groups of mice with both immunization methods. IgG2a was predominant in C57BL/6 mice after intramuscular immunization. These results suggested the Th1 type of immune response in mice after HBcAg genetic vaccination. HBcAg specific CTL activities were more than 50% in both species of mice with both immunization methods. CONCLUSION: This genetic vaccine of HBcAg shows strong antigenecity in both cellular and humoral immunity. The possibility of its clinical application needs to be further investigated.

Animals↗

Dose-effect of dietary L-arginine supplementation on burn wound healing in rats.

OBJECTIVE: To investigate the dose-effect of dietary L-arginine supplementation on burn wound healing in rats. METHODS: 218 Sprague-Dawley rats (weighing 200-250 g) were subjected to 10% deep partial thickness scald burns and were randomized into six groups. Groups A, B, C, D, E and F received 800, 400, 200, 100, 50 and 0 mg.kg-1.d-1 L-arginine in the form of L-arginine solution, and 0, 727, 1090, 1272, 1364, and 1454 mg.kg-1.d-1 glycine, respectively. Each solution was isonitrogenous. The times of completing re-epithelization were recorded. The contents of hydroxyproline (OHP) in burn wound area (index of reparative collagen synthesis) and the ratios of type I and type III collagen were examined in all groups. RESULTS: The times of completing re-epithelization (day) in groups A, B, C, D, E, and F were 24.9 +/- 1.95, 22.5 +/- 2.0, 20.2 +/- 2.4, 23.5 +/- 2.6, 23.8 +/- 3.5, and 24.7 +/- 2.3, respectively. The contents of hydroxyproline in groups B, C and D were higher than in groups A, E and F on PBD 7, 10 and 14. The ratios of type I and type III collagen in groups B, C and D were lower than in groups A, E and F. CONCLUSION: Oral dietary L-arginine supplementation from 100 mg.kg-1.d-1 to 400 mg.kg-1.d-1 shortened the times of re-epithelization, increased amounts of hydroxyproline, and accelerated the synthesis of reparative collagen in burn rats.

Animals↗

[Studies on hematopoietic reconstitution by ex vivo expanded human cord blood hematopoietic stem/progenitor cells in SCID mice].

OBJECTIVE: To elucidate the effect of the combination of cytokines on ex vivo expansion and self-renewal potential of human umbilical cord blood hematopoietic stem/progenitor cells. METHODS: CD34+ cells from cord blood were expanded for 14 days in the culture containing FL + Tpo + SCF + IL-6 + IL-3 + G-CSF and the expanded cells were transplanted into sublethally irradiated SCID mice. RESULTS: The expanded cells were engrafted smoothly in the SCID recipients and reconstituted their hematopoiesis. Furthermore, human hematopoietic cells could be detected in the marrow of the recipients 6 weeks after transplantation. CONCLUSION: It is possible to expand hematopoietic cells ex vivo efficiently and maintain concomitantly their self-renewal and hematopoietic reconstitution capacities by the combination of FL + Tpo + SCF + IL-6 + IL-3 + G-CSF.

Animals↗

[A comparative study between clinical response and pathologic changes to preoperative chemotherapy in non-small cell lung cancer].

OBJECTIVE: To study the clinical response to preoperative chemotherapy in relation to pathologic changes in non-small cell lung cancer (NSCLC). METHODS: Forty-six stage I-IIIa NSCLC patients were given 1-2 courses of preoperative chemotherapy with mitomycin C (MMC) 6 mg.M-2 on day 1, vindesine (VDS) 2.5-3 mg.M-2 on day 1, day 8 and/or day 15, and cisplatin (DDP) 90 mg.M-2 on day 1 (MVP regimen). 'The treatment was recycled every 28 days. Clinical response was assessed according to WHO criteria. Pathologic changes of the resected tumor were categorized to 3 grades. Grade I: No tumor under gross and microscopic observation. Grade II: Grossly no tumor present but residual tumor cells under microscopic observation. Grade III: Tumor reduced in size with clear margins; marked tumor cells degeneration and necrosis accompanied with fibrosis. Grade IV: Active proliferation of tumor cells with invasion. Grade I-II was considered to be chemotherapeutically effective. RESULTS: (1) The clinical response rate was higher in patients who had received 2 courses than those received 1 course of treatment. More patients treated with 2 courses had their pathologic changes in Grade I-II than those treated with 1 course of chemotherapy but the response rate was not fully consistent with pathologic grading. (2) Pathologic grading significantly correlated with the extent of tumor involvement but not with the lymph node status. (3) Efficacy of chemotherapy should be evaluated jointly by the clinical response and grading of pathologic changes. (4) Chemotherapy with MVP regimen did not elicit severe toxic side effect. Nor did it lead to operative morbidity, operative mortality and a delay in postoperative recovery. CONCLUSION: Preoperative chemotherapy with MVP regimen is effective in the treatment of NSCLC in stage I-IIIa.

Adult↗

[p16 gene suppresses growth of human esophageal carcinoma cells].

OBJECTIVE: To explore the effect of p16 gene on the growth inhibition of esophageal carcinoma cell line NEC. METHODS: The full length of wild-type p16 cDNA was transfected into the esophageal carcinoma cell line of human fetus induced by N-methyl-N-benzylnitrosamine (NMBzA). In these esophageal carcinoma cell, p16 gene was homozygously deleted. RESULTS: Expression of exogenous p16 gene in NEC cells was identified by dot blot and Western blot analyses. The growth rate of NEC transfected with p16 gene (NEC-p16) was markedly suppressed. Colony formation in soft agar was also decreased significantly. Cell cycle analysis by flow cytometry showed that the number of cells in G1-G0 phase of NEC-p16 cells was significantly increased while cells in S and G2 + M phase was decreased compared to that of the control NEC cells. CONCLUSION: Transduction of wild type p16 gene into p16 gene-depleted esophageal cancer cells can restore its suppressive effect on cell growth by arrest of cell cycle at G1 phase.

Esophageal Neoplasms↗

[Effects of Astragaloside in treating myocardial injury and myocardial Sarco/Endoplasmic Ca(2+)-ATPase of viral myocarditis mice].

OBJECTIVE: To investigate the effects on myocardial injury and sarcoplasmic reticulum (SR) Ca(2+)-ATPase of viral myocarditis mice treated with Astragaloside (AS) and Astragalus Injection (AI). METHODS: Viral myocarditis model was created by intraperitoneal inoculation with coxsackievirus B3m (CVB3m) solution and were divided into model, AS, AI and normal control groups. The mortality, myocardial pathological changes, serum cardiac troponin I (cTnI) and the activity of myocardial Sarco/Endoplasmic Ca(2+)-ATPase (SERCA) were observed. RESULTS: The mortality of model was higher than that of the normal control (P = 0.0042), AS and AI (P < 0.05). The serum level of cTnI of model was significantly higher than that of the normal control (P < 0.001), AS (P < 0.025) and AI (P < 0.05). The myocardial necrosis and inflammatory changes of AS and AI groups were alleviated than that of model (P < 0.01). The activity of myocardial SERCA of model were significantly lower than that of normal control (P < 0.001), AS (P < 0.01) and AI (P < 0.05). CONCLUSIONS: AS and AI have some protecting effects on myocardial injury of viral myocarditis mice. AS is the effective component of Astragalus membranaceus in treating viral myocarditis. One of the mechanisms of Astragalus membranaceus and AS for viral myocarditis mice depriving of the myocardial injury may be due to improve the activity of myocardial SERCA in the mice.

Animals↗

[Clinical and experimental study on treatment of ankylosing spondylitis].

OBJECTIVE: To explore the effect and mechanism of Gubiyin (GBY) in treating ankylosing spondylitis (AS). METHODS: The 70 patients of AS were randomly divided into two groups, 40 patients in the GBY group were treated with GBY and 30 patients treated with indomethacin for control. Animal experiments were also conducted. RESULTS: Clinical observation showed that the markedly effective rate of the GBY group (57.5%) was higher than that of the control group (23.3%, P < 0.01), but the total effective rate of the two groups were similar. The effects of GBY in relieving symptoms of joints, improving function of joints, preventing degeneration of bone and improving laboratory parameters were better than those of indomethacin. In animal experiments, GBY showed its inhibition on granuloma formation, adjuvant arthritis in mice, and IL-1 production of abdominal macrophage and IL-2 production of spleen cell in rats. CONCLUSION: GBY has effects of anti-inflammation, analgesic, immunoregulation, inflammation mediator inhibition and hemorrheology improvement.

Adolescent↗