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Biomedical subjects

Ling Zhang

Publications and source records attributed to Ling Zhang.

At least 127 records · Page 7Linked to original sources
PubMed2004

Poly(ethylene glycol) enhances the surface activity of a pulmonary surfactant.

The primary role of lung surfactant is to reduce surface tension at the air-liquid interface of alveoli during respiration. Axisymmetric drop shape analysis (ADSA) was used to study the effect of poly(ethylene glycol) (PEG) on the rate of surface film formation of a bovine lipid extract surfactant (BLES), a therapeutic lung surfactant preparation. PEG of molecular weights 3,350; 8,000; 10,000; 35,000; and 300,000 in combination with a BLES mixture of 0.5 mg/mL was studied. The adsorption rate of BLES alone at 0.5 mg/mL was much slower than that of a natural lung surfactant at the same concentration; more than 200 s are required to reach the equilibrium surface tension of 25 mJ/m(2). PEG, while not surface active itself, enhances the adsorption of BLES to an extent depending on its concentration and molecular weight. These findings suggest that depletion attraction induced by higher molecular weight PEG (in the range of 8,000 to 35,000) may be responsible for increasing the adsorption rate of BLES at low concentration. The results provide a basis for using PEG as an additive to BLES to reduce its required concentration in clinical treatment, thus reducing the cost for surfactant replacement therapy.

Animals↗
PubMed2004

D1 dopamine receptor regulation of the levels of the cell-cycle-controlling proteins, cyclin D, P27 and Raf-1, in cerebral cortical precursor cells is mediated through cAMP-independent pathways.

Previously, we demonstrated that dopamine D1 receptor (D1R) agonists inhibit epidermal growth factor (EGF)-induced passage of mouse fetal cerebral cortical precursor cells from the G1 phase to the S phase of the cell cycle. Here, we report that this action of D1R agonists may involve regulation of cyclin D, and P27, which respectively promote and suppress the G1 to S transition. Furthermore, regulation of Raf-1, a component of the receptor tyrosine kinase mitogen-activated protein kinase pathway engaged in the mitogenic activity of EGF, may also be involved. Specifically, levels of cyclin D and Raf-1 decrease, whereas those of P27 first increase and then decrease in a dose-dependent fashion in response to the D1R agonist, SKF38393. This agonist also promotes Raf-1 phosphorylation on serine 338 residue, suggesting increased activation of this protein. Only the latter effect can be blocked by adenylyl cyclase (AC) and cAMP-dependent protein kinase A (PKA) inhibitors, and mimicked by agonists of the cAMP signaling pathway. Another D1R agonist, SKF83959, which stimulates phospholipase Cbeta (PLCbeta) but not AC, reduces levels of Raf-1 and cyclin D similar to SKF38393. However, we detected only down-regulation of P27 by this agonist. Additionally, the concentration-dependent patterns of both SKF38393- and SKF83959-induced alterations in the levels of P27 closely resemble the effects of these ligands on the levels of the D1R-PLCbeta-associated second-messenger cascades linker, calcyon. These findings suggest that D1R-induced suppression of the cell cycle progression in EGF-supported fetal cortical precursor cells represents a net effect of competing cell cycle promoting and inhibiting molecular changes, which involve cyclin D, P27 and Raf-1. The data also show that cAMP second messenger cascade is not engaged in the D1R-induced regulation of the levels of these three proteins. Such regulation probably involves PLCbeta-associated pathways.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2004

Cyclin A2 mediates cardiomyocyte mitosis in the postmitotic myocardium.

Cell cycle withdrawal limits proliferation of adult mammalian cardiomyocytes. Therefore, the concept of stimulating myocyte mitotic divisions has dramatic implications for cardiomyocyte regeneration and hence, cardiovascular disease. Previous reports describing manipulation of cell cycle proteins have not shown induction of cardiomyocyte mitosis after birth. We now report that cyclin A2, normally silenced in the postnatal heart, induces cardiac enlargement because of cardiomyocyte hyperplasia when constitutively expressed from embryonic day 8 into adulthood. Cardiomyocyte hyperplasia during adulthood was coupled with an increase in cardiomyocyte mitosis, noted in transgenic hearts at all time points examined, particularly during postnatal development. Several stages of mitosis were observed within cardiomyocytes and correlated with the nuclear localization of cyclin A2. Magnetic resonance analysis confirmed cardiac enlargement. These results reveal a previously unrecognized critical role for cyclin A2 in mediating cardiomyocyte mitosis, a role that may significantly impact upon clinical treatment of damaged myocardium.

Animals↗
PubMed2004

Interleukin-7 and transforming growth factor-beta play counter-regulatory roles in protein kinase C-delta-dependent control of fibroblast collagen synthesis in pulmonary fibrosis.

Transforming growth factor-beta (TGF-beta) is a potent fibrogenic factor responsible for promoting synthesis of extracellular matrix. Interleukin-7 (IL-7) inhibits TGF-beta signaling by up-regulating Smad7, a major inhibitor of the Smad family. In a variety of cells, TGF-beta-mediated activation of target genes requires active protein kinase C-delta (PKC-delta) in addition to Smads (1). We determined the role of PKC-delta in the regulation of pulmonary fibroblast collagen synthesis in response to TGF-beta and IL-7 stimulation. Here we show that TGF-beta and IL-7 have opposing effects on PKC-delta; TGF-beta stimulates, while IL-7 inhibits, PKC-delta activity. IL-7 inhibits TGF-beta-induced PKC-delta phosphorylation at Ser-645 and Thr-505. Inhibition of PKC-delta with specific small inhibitory RNA restores TGF-beta-mediated induction of Smad7 and in parallel significantly reduces TGF-beta-mediated collagen synthesis. Thus, PKC-delta may play a critical role in the pathogenesis of pulmonary fibrosis and may serve as a molecular target for therapeutic intervention to suppress fibrosis.

Blotting, Northern↗
PubMed2004

Intratumoral administration of dendritic cells overexpressing CCL21 generates systemic antitumor responses and confers tumor immunity.

To achieve in situ tumor antigen uptake and presentation, intratumoral administration of ex vivo-generated, gene-modified murine bone marrow-derived dendritic cells (DC) was used in a murine lung cancer model. To attract mature host DC and activated T cells at the tumor site, the DC were transduced with an adenoviral vector expressing secondary lymphoid tissue chemokine (CCL21/SLC). Sixty percent of the mice treated with 10(6) DC-AdCCL21 intratumorally (7-10 ng/ml/10(6) cells/24 h of CCL21) at weekly intervals for 3 weeks showed complete tumor eradication, whereas only 25% of mice had complete resolution of tumors when mice were treated with fibroblasts expressing CCL21. In contrast only 12% of the mice treated with unmodified or control vector modified DC (DC-AdCV) showed complete tumor eradication. DC-AdCCL21 administration led to increases in the CD4(+), CD8(+), and CD3(+)CXCR3(+) T cells, as well as DC expressing CD11c(+) DEC205(+). CD4(+)CD25(+) T-regulatory cells infiltrating the tumors were markedly reduced after DC-AdCCL21 therapy. The tumor site cellular infiltrates were accompanied by the enhanced elaboration of granulocyte macrophage colony-stimulating factor, IFN-gamma, MIG/CXCL9, IP-10/CXCL10, and interleukin 12, but decreases in the immunosuppressive mediators transforming growth factor beta and prostaglandin E(2). DC-AdCCL21-treated tumor-bearing mice showed enhanced frequency of tumor-specific T lymphocytes secreting IFN-gamma, and tumor protective immunity was induced after DC-AdCCL21 therapy. In vivo depletion of IP-10/CXCL10, MIG/CXCL9, or IFN-gamma significantly reduced the antitumor efficacy of DC-AdCCL21. These findings provide a strong rationale for the evaluation of DC-AdCCL21 in cancer immunotherapy.

Adenoviridae↗
PubMed2004

Constrained sessile drop as a new configuration to measure low surface tension in lung surfactant systems.

Existing methodology for surface tension measurements based on drop shapes suffers from the shortcoming that it is not capable to function at very low surface tension if the liquid dispersion is opaque, such as therapeutic lung surfactants at clinically relevant concentrations. The novel configuration proposed here removes the two big restrictions, i.e., the film leakage problem that is encountered with such methods as the pulsating bubble surfactometer as well as the pendant drop arrangement, and the problem of the opaqueness of the liquid, as in the original captive bubble arrangement. A sharp knife edge is the key design feature in the constrained sessile drop that avoids film leakage at low surface tension. The use of the constrained sessile drop configuration in conjunction with axisymmetric drop shape analysis to measure surface tension allows complete automation of the setup. Dynamic studies with lung surfactant can be performed readily by changing the volume of a sessile drop, and thus the surface area, by means of a motor-driven syringe. To illustrate the validity of using this configuration, experiments were performed using an exogenous lung surfactant preparation, bovine lipid extract surfactant (BLES) at 5.0 mg/ml. A comparison of results obtained for BLES at low concentration between the constrained sessile drop and captive bubble arrangement shows excellent agreement between the two approaches. When the surface area of the BLES film (0.5 mg/ml) was compressed by about the same amount in both systems, the minimum surface tensions attained were identical within the 95% confidence limits.

Animals↗
PubMed2004

Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat in mice.

Haploinsufficiency of the transcription factor gene Sim1 has been previously implicated in hyperphagic obesity in humans and mice. To investigate the relation between Sim1 dosage and hyperphagia, we generated sim1-knockout mice and studied their growth and feeding behavior. Heterozygous mice weaned on standard chow consumed 14% more food per day than controls and developed obesity, hyperinsulinemia, and hyperleptinemia. The sim1 heterozygous mice were also significantly longer than controls. Heterozygous animals had modestly increased feeding efficiency, suggesting reduced energy expenditure, but voluntary wheel-running activity did not differ significantly between the two groups. We studied the effect of dietary fat on the feeding behavior of heterozygous sim1 mutant mice. The tempo and severity of weight gain were much greater in animals weaned on a high-fat diet. When acutely challenged with increased dietary fat, sim1 heterozygous mice weaned on the chow diet markedly increased their food consumption and caloric intake, whereas control mice reduced the mass of food they consumed and maintained approximately isocaloric intake. In wild-type adult mice, we detected Sim1 expression in the paraventricular and supraoptic nuclei, as previously reported in neonates, as well as in the amygdala and lateral hypothalamus, all regions implicated in feeding behavior. Our results indicate that Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat and likely plays a physiological role in the regulation of energy balance.

Aging↗
PubMed2004

Rapid and sensitive dot-matrix methods for genome analysis.

MOTIVATION: Dot-matrix plots are widely used for similarity analysis of biological sequences. Many algorithms and computer software tools have been developed for this purpose. Though some of these tools have been reported to handle sequences of a few 100 kb, analysis of genome sequences with a length of >10 Mb on a microcomputer is still impractical due to long execution time and computer memory requirement. RESULTS: Two dot-matrix comparison methods have been developed for analysis of large sequences. The methods initially locate similarity regions between two sequences using a fast word search algorithm, followed with an explicit comparison on these regions. Since the initial screening removes most of random matches, the computing time is substantially reduced. The methods produce high quality dot-matrix plots with low background noise. Space requirements are linear, so the algorithms can be used for comparison of genome size sequences. Computing speed may be affected by highly repetitive sequence structures of eukaryote genomes. A dot-matrix plot of Yeast genome (12 Mb) with both strands was generated in 80 s with a 1 GHz personal computer.

Algorithms↗
PubMed2004

Statistics-based approach for aneurysm volume measurements.

PURPOSE: To evaluate the ability of high-resolution MRA to monitor changes in intracranial aneurysm volume, and devise a highly reliable technique for obtaining these measurements. MATERIALS AND METHODS: To obtain a baseline estimate of the repeatability of MRA scans and validate the statistics-based technique for aneurysm volume measurement, multiple scans were obtained on individual subjects over a period of up to 1 year. These 3D MRA data sets were coregistered and then analyzed using the volumetric analysis of segmented data and the proposed statistical method. RESULTS: It was shown that high-resolution MRA provides highly repeatable data sets. Both methods used for the aneurysm volume measurements showed consistent results. However, the proposed statistical method had lower error and was much less sensitive to the choice of segmentation parameter than the volumetric analysis of segmented data. A change of 1 mm in the average radius of the aneurysm was detectable with the statistics-based technique. CONCLUSIONS: This study demonstrates that the statistical method of aneurysm volume measurement in high-resolution MRA allows reliable and accurate assessments of aneurysm volume changes.

Cerebrovascular Circulation↗
PubMed2004

Immunopotentiating effect of a 'Yang'-promoting formula of traditional Chinese medicine on aged female BALB/c mice.

The 'Yang'-promoting traditional Chinese medicines (TCM) are used to boost vigor and enhance immunity in humans. In this study, the immunopotentiating effect of VI-28, a 'Yang'-promoting TCM formula containing extracts of radix ginseng, cornu Cervi pantotrichum and radix Salvia miltiorrhizae, was investigated. Groups of 8-month-old female ex-breeder BALB/c mice were fed on ordinary mouse food or food containing a low (0.5%) or high (2%) dose VI-28 for up to 18 weeks. From week 6, mice on the TCM-containing diet were much healthier, stronger and more alert than those on the normal mouse food. Furthermore, their thymuses were significantly bigger and heavier than those of the control mice. Histological examination revealed structural changes typical of thymic involution in mice of the control group, whilst the microstructure of thymuses from mice taking TCM-containing food was comparable to that of mice of a much younger age, indicating a positive effect of VI-28 on slowing down thymic involution. Functional analysis of splenocytes from mice of different groups suggested that oral administration of VI-28 corrected the hyporesponsiveness of T lymphocytes in aged mice. These results have important implications for our understanding of the mechanisms of the immunoboosting effect of TCM.

Aging↗
PubMed2004

Mass screening of prostate cancer in Changchun City of China.

OBJECTIVES: Mass screening of prostate cancer in China had not been studied until now. To clarify the incidence of prostate cancer among the population of aged men in Changchun City of China, we performed a mass screening program for prostate cancer using prostate specific antigen (PSA). METHODS: Men aged more than 50 years were examined by PSA, with a cut-off values 4.1 ng/ml. Subjects, whose serum PSA concentration was more than 4.1 ng/ml, were recommended to secondary examination of transrectal ultrasound-guided systematic six-sextant biopsy examination (TRUS-guided biopsy). RESULTS: Between April 1998 and December 2000, in the urban area of Changchun City 4218 men over 50 years old were screened. As 190 men were found to have elevated PSA and 116 men underwent a TRUS-guided biopsy of the prostate, of whom 29 men were found to have cancer. In all, the age-adjusted PSA positive rate was 4.80%, cancer detection rate was 0.74%. The age-adjusted cancer detection rate was 0.78%. After adjusted for secondary examination rate, the cancer detection rate reached 1.28%. The cases of stage B with limited cancer within the prostate gland, accounted for 62% of 29 cancer cases. Stage B was much more detected (accounted for 60%) in the PSA range of 4.1-10.0 ng/ml. Stage C and D were much more detected (accounted for 85.71%) in the PSA range over 10.1 ng/ml, with a significant difference by Fisher exact test (P < 0.05). A significant correlation of age-adjusted PSA positive rate and age-adjusted cancer detection rate adjusted by secondary examination rate was showed in six groups of Community and Army, Factory, Corporation, Post and Telecom Office, Government and Academy, and University and Technical School (r = 0.898, P < 0.01). Both of the age-adjusted PSA positive rate and age-adjusted cancer detect rate of "Universities and Technical Schools" were significantly higher than that of "Factories" (chi2 test P < 0.05). CONCLUSIONS: The prevalence of prostate cancer was not so low in Chinese people as expected. For 50 years or older men, cancer detection rate was 0.74%, The age-adjusted cancer detect rate was 0.78%. Much more early stage cancer could be detected in the screening using serum PSA. For the different company the detection rate of prostate cancer varied each other among the groups. Age-adjusted cancer detection rate in "Universities and Technical Schools" were significantly higher than in "Factories", suggesting environment factor or diet might be associated with the prostate cancer.

Age Factors↗
PubMed2004

Steroids from the roots of Cynanchum stauntonii.

A chemical investigation of the roots of Cynanchum stauntonii has resulted in the characterization of a new hydroperoxide with a 13,14 : 14,15-disecopregnane-type skeleton, named stauntonine (1), together with three related compounds, anhydrohirundigenin (2), anhydrohirundigenin monothevetoside (3), and glaucogenin-C mono- D-thevetoside (4). Their structures were established by spectroscopic methods, including X-ray crystallographic diffraction analysis of stauntonine that confirmed its relative stereochemistry. The compound 1 showed dose-dependent relaxation on aortic rings with endothelium contracted by phenylepherine or KCl.

Animals↗
PubMed2004

Microarray analysis of temperature-induced transcriptome of Yersinia pestis.

Yersinia pestis, the etiologic agent of plague, must acclimatize itself to temperature shifts between the temperature (26 C) for flea blockage and the body temperature (37 C) of warm-blooded hosts during its life cycle. Here a whole-genome DNA microarray was used to investigate transcriptional regulation upon the upshift of growth temperature from 26 to 37 C in a chemically defined medium. Four hundred and one genes were regulated differentially under the two temperatures. About 39% of these genes were up-regulated at 37 C, whereas 61% were down-regulated. Temperature-induced changes occurred at the level of transcription of genes encoding proven or predicted virulence factors, regulators, metabolism-associated proteins, prophages, and hypothetical proteins. Strikingly, many gene clusters displayed a co-transcription pattern in response to temperature upshift. Our data provided a genome-wide profile of gene transcription induced by temperature shift and should shed light on the pathogenicity and host-microbe interaction of this deadly pathogen.

Animals↗
PubMed2004

Effects and mechanism of the selective COX-2 inhibitor, celecoxib, on rat colitis induced by trinitrobenzene sulfonic acid.

OBJECTIVE: To investigate the action of celecoxib (a selective COX-2 inhibitor) in a rat model of colitis induced by trinitrobenzene sulfonic acid (TNBS). METHODS: Rats were randomized into four groups. Colitis was induced in groups 1 and 2 by intracolonic administration of TNBS (25 mg/mL) in 50% ethanol (0.25 mL). The rats in group 1 received oral celecoxib (1.25 mg/kg) and those in group 2 received distilled water (1 mL/0.3 kg), beginning 3 h before induction of colitis and continuing twice daily thereafter for up to 7 days. The rats in group 4 received oral celecoxib (1.25 mg/kg) twice daily for 7 days and those in group 3 were healthy controls. All rats that survived 7 days were killed and both the severity of colonic mucosal damage and the prostaglandin E2 (PGE2) concentrations of the colonic mucosa were assessed. RESULTS: The colonic mucosal damage scores for groups 1 and 2 were 11.15 +/- 3.30 and 8.50 +/- 2.82, respectively, both of which were significantly higher than the score for the healthy controls (0.62 +/- 0.09; P < 0.01, P < 0.01). The score of group 1 was significantly higher than that of group 2 (P < 0.05). No difference was found between the scores of groups 3 and 4. The mucosal concentrations of PGE2 in groups 1 and 2 were 12.00 +/- 4.33 pg/microg and 17.20 +/- 9.62 pg/microg, respectively, both of which were significantly higher than the concentration in the healthy controls (6.02 +/- 3.39 pg/microg; P < 0.05, both). The PGE2 concentration of group 1 was decreased significantly compared with that of group 2 (P < 0.05). No difference was found between groups 3 and 4. CONCLUSION: The results suggest that treatment with celecoxib exacerbates inflammation-associated colonic injury in experimental colitis induced by TNBS. This preliminary study shows that the mechanism is related to suppression by the COX-2 inhibitor of the PG derived from COX-2, but further study is needed to identify if there are other related mechanisms.

Animals↗
PubMed2004

Feitai attenuates bleomycin-induced pulmonary fibrosis in rats.

Pulmonary fibrosis is a common consequence of numerous pulmonary diseases. The current therapeutic approaches for this condition are unsatisfactory. Feitai, a composite formula consisting of several herbs, is used in China as a folk remedy for treating patients with pulmonary tuberculosis. In this study, we extensively investigate the effects and mechanisms of Feitai on bleomycin (BLM)-induced pulmonary fibrosis in rats. One hundred and twenty male Sprague-Dawley rats were randomly divided into four groups, referred to as the saline-water, saline-Feitai, BLM-water, and BLM-Feitai groups. Following a single instillation of BLM (5 mg/kg) or saline, rats were orally administered Feitai at a dose of 3 g/kg body weight or sterilized distilled water once daily. Rats were killed at 7, 14, or 28 d post-BLM. Inflammatory cell count, protein concentration, and lactate dehydrogenase activity in bronchoalveolar lavage fluid were measured, and myeloperoxidase activity and lipid peroxide content in lung homogenates were analyzed. Treatment with Feitai inhibited lung fibrotic progression induced by BLM, as indicated by the decrease in lung hydroproline content and lung fibrosis score at 28 d post-BLM. This was accompanied by significant amelioration of BLM-induced body weight loss, lung edema, and inflammatory response during the development of lung injury in the acute phase. The results strongly indicate the beneficial effects of Feitai in protecting against BLM-induced pulmonary fibrosis. Furthermore, the inflammatory response and lipid peroxidation were inhibited by Feitai, suggesting that the effect of this formula on BLM-induced lung injury and fibrosis is associated with antiinflammatory and antioxidant properties.

Animals↗
PubMed2004

Mass screening of 12,027 elderly men for prostate carcinoma by measuring serum prostate specific antigen.

BACKGROUND: The incidence of prostate carcinoma (Pca) has been increasing in China. We detected Pca in elderly men in Changchun, north China and the significance of prostate specific antigen (PSA) in mass screening and clinical staging of Pca. METHODS: Serum PSA from 12,027 men over 50 years old from Changchun was analyzed. In case of serum PSA greater than 4.0 ng/ml, the patient was suspected of potentially suffering from Pca, and transrectal six-point puncture prostate biopsies were performed under ultrasound guidance. Pathological examinations were performed on the biopsy tissue, and ABCD and TNM clinical stagings were used in accordance with international standards. Correlations between serum PSA level and clinical stage were analyzed. RESULTS: PSA was greater than 4.0 ng/ml in 813 patients (6.8% of the 12,027 men). Transrectal six-point prostate puncture biopsies guided by ultrasound were performed in 273 patients (33.6% of the 813 patients who were tested positive in the initial mass screening). Of these 273 patients, 69 cases of Pca (25.3% of 273) were confirmed by biopsy in the second screening, with an overall detection rate for Pca of 0.57% (69/12,027). The total number of patients in stages A, B, T1, or T2 was 57.9%, and over 20% of them suffered from late stage Pca with lymph node and bone metastasis. An obvious positive correlation was observed between ABCD staging, TNM staging, and serum PSA level. CONCLUSIONS: Serum PSA level is not only the golden standard for mass screening of Pca, but also the predictor for clinical stage of Pca. PSA testing revealed asymptomatic Pca cases in early, middle, and later stages in the elderly, suggesting that mass screening is of paramount importance.

Aged↗
PubMed2004

Establishment of transgenic mouse model carring the promoter of plunc sequence.

OBJECTIVE: To construct the vector using specific nasopharynx tissue promoter plunc to establish transgeneic mouse model. METHODS: Plunc-EGFP plasmid was digested with XhoI, the purified linearized DNA fragments were recovered by gel extraction and diluted to the final concentration of 4 microg/ml, before introduced into fertilized one-cell mouse eggs by pronuclear microinjection. RESULTS: Thirteen founder mice were obtained, 12 of which were positive for the integrated EGFP gene as detected by PCR, and 3 were positive shown by Southern blotting. CONCLUSION: Specific nasopharynx tissue promoter plunc can effectively induce exogenous gene integration into the mouse genome.

Animals↗