Biomedical subjects

Ping Wang

Publications and source records attributed to Ping Wang.

At least 343 records · Page 19Linked to original sources

PubMed2002

Mating-type-specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans.

Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving fusion of haploid MATalpha and MATa cells. Virulence has been linked to the mating type, and MATalpha cells are more virulent than congenic MATa cells. To study the link between the mating type and virulence, we functionally analyzed three genes encoding homologs of the p21-activated protein kinase family: STE20alpha, STE20a, and PAK1. In contrast to the STE20 genes that were previously shown to be in the mating-type locus, the PAK1 gene is unlinked to the mating type. The STE20alpha, STE20a, and PAK1 genes were disrupted in serotype A and D strains of C. neoformans, revealing central but distinct roles in mating, differentiation, cytokinesis, and virulence. ste20alpha pak1 and ste20a pak1 double mutants were synthetically lethal, indicating that these related kinases share an essential function. In summary, our studies identify an association between the STE20alpha gene, the MATalpha locus, and virulence in a serotype A clinical isolate and provide evidence that PAK kinases function in a MAP kinase signaling cascade controlling the mating, differentiation, and virulence of this fungal pathogen.

Alleles↗

PubMed2002

MMP inhibition modulates TNF-alpha transgenic mouse phenotype early in the development of heart failure.

Myocardial extracellular matrix remodeling regulated by matrix metalloproteinases (MMPs) is implicated in the progression of heart failure. We hypothesized that MMP inhibition may modulate extracellular matrix remodeling and prevent the progression of heart failure. The effects of the MMP inhibitor BB-94 (also known as batimastat) on MMP expression, collagen expression, collagen deposition, collagen denaturation, and left ventricular structure and function in transgenic mice with cardiac-restricted overexpression of tumor necrosis factor-alpha (TNF-alpha) (TNF1.6) were assessed. The results showed that BB-94 reduced the expression of collagens, increased insoluble collagen and the ratio of undenatured to total soluble collagen, and prevented myocardial hypertrophy and diastolic dysfunction in young TNF1.6 mice. Furthermore, the treatment significantly improved cumulative survival of TNF1.6 mice. However, MMP inhibition did not have salutary effects on ventricular size and function in old mice with established heart failure. The results suggest that MMP activation may play a critical role in changes of myocardial function through the remodeling of extracellular matrix, and MMP inhibition may serve as a potential therapeutic strategy for heart failure, albeit within a narrow window during the development of heart failure.

Animals↗

PubMed2002

Alveolar macrophage activation after trauma-hemorrhage and sepsis is dependent on NF-kappaB and MAPK/ERK mechanisms.

The acute respiratory distress syndrome (ARDS) is a major cause of morbidity after injury. We hypothesized that alveolar macrophage (AMPhi) chemokine and cytokine release after hemorrhage and sepsis is regulated by NF-kappaB and MAPK. Adult male rats underwent soft tissue trauma and hemorrhagic shock (~90 min) followed by crystalloid resuscitation. Sepsis was induced by cecal ligation and puncture (CLP) 20 h after resuscitation. AMPhi were harvested, and TNF-alpha, IL-6, and macrophage inflammatory protein (MIP)-2 release and serum IL-6 and TNF-alpha levels were measured at 5 h after HCLP. Lung tissues were analyzed for activation of NF-kappaB, myeloperoxidase activity, and wet/dry weight ratio. In control animals, AMPhi were stimulated with LPS with or without inhibitors of NF-kappaB and MAPK. Serum TNF-alpha and IL-6 levels and spontaneous AMPhi TNF-alpha and MIP-2 release were elevated (P < 0.05) after HCLP, concomitantly with the development of lung edema and leukocyte activation. Activation of NF-kappaB increased in lungs from the hemorrhage and CLP group compared with shams. Inhibition of NF-kappaB or the upstream MAPK significantly decreased LPS-stimulated AMPhi activation. Because enhanced release of inflammatory mediators by AMPhi may contribute to ARDS after severe trauma, inhibition of intracellular signaling pathways represents a target to attenuate organ injury under those conditions.

Animals↗

PubMed2002

Adrenomedullin binding protein-1 modulates vascular responsiveness to adrenomedullin in late sepsis.

Adrenomedullin (AM), a potent vasodilatory peptide, plays an important role in initiating the hyperdynamic response during the early stage of sepsis. Moreover, the reduced vascular responsiveness to AM appears to be responsible for the transition from the early, hyperdynamic to the late, hypodynamic phase of sepsis. Although the novel specific AM binding protein-1 (AMBP-1) enhances AM-mediated action in a cultured cell line, it remains to be determined whether AMBP-1 plays any role in modulating vascular responsiveness to AM during sepsis. To study this, adult male rats were subjected to sepsis by cecal ligation and puncture (CLP). The thoracic aorta was harvested for determination of AM-induced vascular relaxation. Aortic levels of AMBP-1 were determined by Western blot analysis, and AM receptor gene expression in the aortic tissue was assessed by RT-PCR. The results indicate that AMBP-1 significantly enhanced AM-induced vascular relaxation in aortic rings from sham-operated animals. Although vascular responsiveness to AM decreased at 20 h after CLP (i.e., the late, hypodynamic stage of sepsis), addition of AMBP-1 in vitro restored the vascular relaxation induced by AM. Moreover, the aortic level of AMBP-1 decreased significantly at 20 h after CLP. In contrast, AM receptor gene expression was not altered under such conditions. These results, taken together, suggest that AMBP-1 plays an important role in modulating vascular responsiveness to AM, and the reduced AMBP-1 appears to be responsible for the vascular AM hyporesponsiveness observed during the hypodynamic phase of sepsis.

Adrenomedullin↗

PubMed2002

The contentious nature of gestational diabetes: diet, insulin, glyburide and metformin.

Gestational diabetes (GD) develops because pregnancy increases requirements for insulin secretion while increasing insulin resistance. Women with GD often have impaired pancreatic beta-cell compensation for insulin resistance. The nature of GD is currently contentious, with debate about its existence, diagnosis and ramifications for both mother and offspring from pregnancy into later life. Also contentious are the outcomes of intervention with diet, insulin, glyburide (Glynase trade mark, Pharmacia Upjohn) and metformin (Glucophage trade mark, Bristol-Myers Squibb). There is consensus that women with unequivocal GD have a significant risk of adverse perinatal outcomes and increased risk of later type 2 diabetes mellitus. Foetuses from pregnancies with GD have a higher risk of macrosomia (associated with higher rate of birth injuries), asphyxia, and neonatal hypoglycaemia and hyperinsulinaemia. Uncontrolled GD predisposes foetuses to accelerated, excessive fat accumulation, insulin resistance, pancreatic exhaustion secondary to prenatal hyperglycaemia and possible higher risk of child and adult obesity and type 2 diabetes mellitus later in adult life. However, there is no consensus as to whether glucose intolerance of a severity below unequivocal GD is related to adverse maternal, fetal or perinatal outcomes, and whether this relationship is a continuous one. If dietary intervention is not sufficient in the treatment of GD, then, historically, insulin has been added. Recent studies suggest that glyburide may be efficaciously substituted for insulin. Preliminary studies suggest that metformin may have the unique potential to prevent the development of GD.

Clinical Trials as Topic↗

PubMed2002

Treatment of polycystic ovary syndrome with insulin-lowering agents.

Early diagnosis and therapy of the underlying insulin resistance of heritable polycystic ovary syndrome (PCOS), often manifested at menarche, facilitate the reduction and/or reversal of the reproductive and metabolic morbidity of PCOS, as well as reduce the risk factors for cardiovascular disease. PCOS is characterised by oligoamenorrhoea, clinical and biochemical hyperandrogenism, infertility, recurrent miscarriage, insulin resistance, hyperinsulinaemia, gestational diabetes, impaired glucose tolerance, Type 2 diabetes, morbid obesity, hypertension, hypofibrinolysis, hypertriglyceridaemia, low levels of high density lipoprotein-cholesterol and a sevenfold risk increase in cardiovascular disease. Insulin sensitising-lowering agents reduce insulin resistance and hyperinsulinaemia, reverse PCOS endocrinopathy and ameliorate the reproductive, metabolic and cardiovascular morbidity of the disorder. The largest literature on the subject discusses metformin. Improved pregnancy outcomes in women with PCOS receiving metformin may be attributed to its ability to reduce insulin resistance, hyperinsulinaemia and hypofibrinolytic plasminogen activator inhibitor activity by the enhancement of folliculogenesis and improvement of oocyte quality.

Female↗

PubMed2002

The role of endotoxin, TNF-alpha, and IL-6 in inducing the state of growth hormone insensitivity.

AIM: Critical illnesses such as sepsis, trauma, and burns cause a growth hormone insensitivity, which leads to an increased negative nitrogen balance. Endotoxin is generously released into blood under these conditions and stimulates the production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1, which may play a very important role in inducing the growth hormone insensitivity. The objective of this current study was to investigate the role of endotoxin, TNF-alpha and IL-6 in inducing the growth hormone insensitivity at the receptor and post-receptor levels. METHODS: Spague-Dawley rats were injected with endotoxin, TNF-alpha, and IL-6, respectively and part of rats injected with endotoxin was treated with exogenous somatotropin simultaneously. All rats were killed at different time points. The expression of IGF-I, GHR, SOCS-3 and beta-actin mRNA in the liver was detected by RT-PCR and the GH levels were measured by radioimmunoassay, the levels of TNF-alpha and IL-6 were detected by ELISA. RESULTS: There was no significant difference in serous GH levels between experimental group and control rats after endotoxin injection, however, liver IGF-I mRNA expression had been obviously down-regulated in endotoxemic rats. Liver GHR mRNA expression also had a predominant down-regulation after endotoxin injection. The lowest regulation of liver IGF-I mRNA expression occurred at 12h after LPS injection, being decreased by 53% compared with control rats. For GHR mRNA expression, the lowest expression occurred at 8h and had a 81% decrease. Although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up-regulated after LPS injection and had a 7.84 times increase compared with control rats. Exogenous GH could enhance IGF-I mRNA expression in control rats, but it did fail to prevent the decline in IGF-I mRNA expression in endotoxemic rats. Endotoxin stimulated the production of TNF-alpha and IL-6, and the elevated IL-6 levels was shown a positive correlation with increased SOCS-3 mRNA expression. The liver GHR mRNA expression was obviously down-regulated after TNF-alpha iv injection and had a 40% decrease at 8h, but the liver SOCS-3 mRNA expression was the 4.94 times up-regulation occurred at 40 min after IL-6 injection. CONCLUSION: The growth hormone insensitivity could be induced by LPS injection, which was associated with down-regulated GHR mRNA expression at receptor level and with up-regulated SOCS-3 mRNA expression at post-receptor level. The in vivo biological activities of LPS were mediated by TNF-alpha and IL-6 indirectly, and TNF-alpha and IL-6 may exert their effects on the receptor and post-receptor levels respectively.

Animals↗

PubMed2002

[Expression and significance of platelet derived growth factor and its receptor in liver tissues of patients with liver fibrosis].

OBJECTIVE: To study the expression and significance of platelet derived growth factor (PDGF) and its receptor (PDGFR) in liver tissues of patients with chronic hepatitis fibrosis and liver cirrhosis. METHODS: The expression, distribution, quantitation, and correlation of PDGF-A, PDGF-B, PDGFR-alpha, PDGFR-beta, and alpha-SMA in the liver tissues were analyzed by immunohistochemical techniques in 21 patients with chronic hepatitis and 42 patients with liver cirrhosis. RESULTS: In the liver tissues of chronic hepatitis and liver cirrhosis, PDGF and its receptor and alpha-SMA mainly distributed in the fibrotic septa and the infiltration area of inflammation, particularly in branch spindle-shaped cells (activated HSC). The expression of PDGF-B and PDGFR-beta was stronger than that of PDGF-A and PDGFR-alpha with a significant difference between them (P<0.05 approximately 0.01). The expression and distribution of alpha-SMA was basically identical with the expression and distribution of PDGF-A, PDGF-B and PDGFR-alpha, PDGFR-beta and quantitative analysis showed a positive correlation (r=0.606, P<0.001). CONCLUSIONS: PDGF and PDGFR play a key role in liver fibrogenesis and development. The biologic effects of PDGF are elicited through activising HSC. Inhibiting PDGF and its receptor is a new approach to the treatment of liver fibrosis.

Actins↗

PubMed2002

Mechanism of growth hormone insensitivity induced by endotoxin.

AIM: To investigate the mechanism of growth hormone (GH) insensitivity induced by endotoxin at receptor and post-receptor levels. METHODS: Sprague-Dawley rats were injected endotoxin along with or without GH administration. The liver expression of insulin-like growth factor I (IGF-I), GH receptor (GHR), and suppresor of cytokine signaling (SOCS)-3 mRNA were detected by reverse transcriptase polymerase cha in reaction, the GH levels were measured by radioimmunoassay, the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay. RESULTS: Serum GH levels had no significant difference compared with control rats after endotoxin injection, however, liver IGF-I mRNA expression was obviously down-regulated in endotoxemic rats. Liver GHR mRNA expression was predominantly down-regulated after LPS injection; although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up-regulated in endotoxemic rats. Endotoxine stimulated the production of TNF-alpha and IL-6, and the elevated IL-6 levels showed a positive correlation with increased SOCS-3 mRNA expression. Exogenous GH could enhance IGF-I mRNA expression in control rats, but it did fail to prevent the decline in IGF-I mRNA expression in endotoxemic rats. Two different LPS dosages (7.5 mg/kg and 5.0 mg/kg) produced the same down-regulation of IGF-I mRNA expression, however, the higher LPS dosage induced more GHR mRNA down-regulation and more SOCS-3 mRNA up-regulation. CONCLUSION: The mechanism of growth hormone insensitivity induced by endotoxin was associated with down-regulated GHR mRNA expression at receptor level and up-regulated SOCS-3 mRNA expression at post-receptor level. The inhibition at post-receptor level had close relationship with the increased IL-6 secretion.

Animals↗

PubMed2002

The cardiovascular response in sepsis: proposed mechanisms of the beneficial effect of adrenomedullin and its binding protein (review).

Sepsis and its complications are leading causes of morbidity and mortality. A better understanding of the mechanisms responsible for the shift from the early, hyperdynamic phase of sepsis to the late hypodynamic phase could lead to novel therapies that might improve the outcome of the septic patient. Adrenomedullin is a vasodilatory peptide which shows sustained elevation starting early in sepsis and is important in initiating the hyperdynamic response. As sepsis progresses, however, the vascular response to adrenomedullin is blunted and this decreased sensitivity is important in producing the shift to the late, hypodynamic phase. The decline in the vascular response to adrenomedullin is related to a sepsis-induced decrease in the binding protein for adrenomedullin (i.e., adrenomedullin binding protein-1) rather than a change in gene expression of the components of adrenomedullin receptors. Treatment of septic animals with the combination of adrenomedullin and its binding protein prevents the transition to the late phase of sepsis, maintains cardiovascular stability, and reduces sepsis-induced mortality. We propose that the mechanisms responsible for the beneficial effect of adrenomedullin and adrenomedullin binding protein-1 in sepsis are associated with downregulation of proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6), maintainence of endothelial constitutive nitric oxide synthase, and reduction of vascular endothelial cell apoptosis.

Adrenomedullin↗

PubMed2002

Expression and immunocompetence identification of Plasmodium falciparum glutamate dehydrogenase.

OBJECTIVE: To express the fusion protein of glutamate dehydrogenase (GDH) with glutathione S-transferase (GST) of Plasmodium falciparum FCC1/HN in E. coli BL21 and assess the immunocompetence of the recombinant protein. METHODS: GDH gene of P. falciparum was specifically amplified with PCR, followed by double enzyme digestion and cloning the gene fragment into pGEX-4T-1 vector for the expression of the fusion protein GST. The recombinant plasmid was transformed into E. coli BL21. Four mice (Kunming strain) were immunized with purified recombinant protein (antigen) and the polyclonal antibodies produced in response to the treatment were collected. Enzyme-linked immunosorbent assay and Western blotting were carried out to examine the immunocompetence of the recombinant protein. RESULTS: The fusion protein was successfully expressed, which exhibited specific reaction with the sera obtained from mice immunized with P. falciparum. Specific humoral responses were elicited after introducing the fusion protein in mice and the specific antibody titer was 1:16 in agar diffusion assay. CONCLUSION: GDH of P. falciparum may have successful expression in E. coli BL21 and the expressed protein possesses high antigenicity.

Animals↗

PubMed2002

[Application of phage antibody library technology: problems and their solutions].

In spite of the wide application of phage antibody library technology in antibody engineering, problems are often present especially in the key steps, for instance, library construction, screening and expression of the antibody. The authors conducted an analysis of these problems and thereby proposes their solutions.

Antibodies↗

PubMed2002

Sixty-seven cases of abnormal movement of the cardiac apex treated with bu xin tang.

Bu Xin Tang (heart-reinforcement decoction) was used to treat 67 cases of abnormal movement of the cardiac apex based on differentiation of symptoms and signs. The results showed that, in most patients, there were remarkable improvement not only for the symptoms but also for the abnormal movement of the cardiac apex. The cured plus remarkably effective rate was 87%, suggesting that it can postpone or prevent coronary heart attacks for the patient of prophase coronary heart disease.

Adult↗

PubMed2002

Cloning of full length cDNA sequence of the mouse ameloblastin.

OBJECTIVE: Screening for special genes of matrix proteins of dentin and enamel of mouse dental germ. METHODS: A cDNA library of dental germ of mouse was screened by differential display. The interesting clones were sequenced. RESULTS: Six positive clones were isolated from the cDNA library. The sequence of one of the six positive clones was homologous with the ameloblastin sequence of rat. There are 497 homologous base pairs between the 526 base pairs sequenced by pTriplEX 3' primer of this clone and the 32-580 sequence of the rat ameloblastin gene; and there are 533 homologous base pairs between the 567 base pairs sequenced by pTriplEX 5' primer of this clone and the 1285-1854 sequence of the rat ameloblastin gene. CONCLUSIONS: The full length cDNA sequence of the mouse ameloblastin was cloned.

Amino Acid Sequence↗

PubMed2002

Effects of repeated + Gz forces on masticatory muscles.

OBJECTIVE: To study the effects of repeated + Gz forces on masticatory muscles. METHODS: 48 male Wistar rats were randomly divided into 4 groups. Group A was normally fed. Group B was only fixed with rat-kept devices for 5 minutes. Group C was borne + 1 Gz for 5 minutes. Group D was repeatedly exposed + 10 Gz (each for 30 s, onset rate about 0.5 G/s, 5 times/d with + 1 Gz 1 minute intervals, 4 d/wk, 3 weeks in total). The histological changes of the masseter, temporal and lateral pterygoid muscles were observed. RESULTS: No abnormal changes were observed in Group A, B and C. But pathological changes could be found in group D. The wrench and deformation of muscular fibers, the dissolution of partial myofibril, the swelling of mitochondria, the reduce of hepatin from the masseter and lateral pterygoid muscles could be found. CONCLUSIONS: Repeated + Gz stresses could induce the damage of masticatory muscles in different degrees.

Animals↗

PubMed2002

[Identification of the binding site on ICAM-1 for red blood cells infected by Plasmodium falciparum].

OBJECTIVE: To identify the binding site on ICAM-1 to PRBCs in order to explore anti-adhesive agent against cerebral malaria. METHODS: Monoclonal antibody 15.2 against ICAM-1 domain 1 was chosen as target molecule to screen mimetic peptides of ICAM-1 from a 12-mer random peptide library. Three rounds of biopanning were carried out and then ELISA, competitive ELISA, dot-ELISA and Western blotting were used to evaluate the binding character between phage-borne peptides and McAb 15.2. The insert DNA sequences of positive clones were determined and their amino acid sequences were deduced. RESULTS: Thirty clones from the third round were randomly selected, and 26 of them were found positive by sandwich ELISA. The competitive ELISA test proved that most phage-borne peptides could competitively inhibit the binding of antibody (15.2 McAb) with ICAM-1. Analysis of DNA and amino acid sequences indicated that over a half positive phage clones expressed 12-mer peptide KLYLIAEGSVAA. Comparison of peptide K(XX) L(XXX) GSV with the 64-73 aa of primary sequence of ICAM-1 showed a 50% homogeneity. CONCLUSION: These peptides displayed by phage may be analogs of ICAM-1, K..L...GSV probably plays a significant role on the binding reaction of ICAM-1 and PRBCs.

Amino Acid Sequence↗

PubMed2002

Telomerase activity in urine in diagnosis and recurrence surveillance of urothelial carcinoma.

OBJECTIVE: To investigate the significance of telomerase activity in urine in the diagnosis and recurrence surveillance of urothelial carcinoma. METHODS: Telomerase activity in urine of 54 cases of urothelial carcinoma (urothelial carcinoma group) was estimated by polymerase chain reaction-enzyme-linked immunosorbent assay, and monitored continuously in 23 cases after tumor removal. 46 patients with benign urological diseases were also included as the control group. RESULTS: The telomerase activity in urine of patients with urothelial carcinoma increased significantly as compared with the control group (P < 0.001), decreased into the normal range after tumor removal, and rose again upon intravesical tumor recurrence before the screening of recurrent tumors by cystoscopy. The higher the grade of tumor, the higher the telomerase activity; no correlation could be found between the preoperative level of telomerase activity in urine and recurrence. CONCLUSIONS: The examination of telomerase activity in urine is helpful in the diagnosis of urothelial carcinoma and may be related to the differentiation degree of tumors. Its sensitivity is higher than that of cystoscopic examination and may become an important ancillary method in the screening of urothelial carcinoma recurrence.

Female↗

PubMed2002

[Growth hormone insensitivity of rats under the endotoxemic condition].

OBJECTIVE: To investigate the mechanism of growth hormone insensitivity of rats under the endotoxemic condition. METHODS: Sprague Dawley rats (n = 180) were injected endotoxin, TNF-alpha, and IL-6 respectively. Part of endotoxin injected rats were treated with exogenous somatotropin simultaneously, and all rats were killed at different time points. Liver expression of IGF I, GHR and SOCS-3 mRNA was detected by RT-PCR, the levels of growth hormone (GH) were measured by radioimmunoassay, and the levels of TNF-alpha and IL-6 were detected by ELISA. RESULTS: Serum GH levels showed no significant change after endotoxin injection; however, liver IGF I and GHR mRNA expressions were obviously down-regulated in endotoxemic rats, with the lowest decrease of 53% and 89% respectively. Although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up-regulated in endotoxemic rats and the marked increase was 7.84 folds. The higher LPS dosage induced marked GHR mRNA down-regulation and marked SOCS-3 mRNA up-regulation. Exogenous GH made IGFI mRNA expression increase 25% in the control rats, but it did fail to prevent the decline in IGFI mRNA expression in endotoxemic rats. Endotoxin stimulated the production of TNF-alpha and IL-6, and the elevated IL-6 levels showed a positive correlation with increased SOCS-3 mRNA expression. Liver GHR mRNA expression was obviously down-regulated after TNF-alpha i.v. injection, but for IL-6, it mainly up-regulated the liver SOCS-3 mRNA expression. CONCLUSION: The growth hormone insensitivity could be induced by LPS injection, which might be associated with down-regulated GHR mRNA expression and up-regulated SOCS-3 mRNA expression. The in vivo biological activities of LPS may be partially mediated by TNF-alpha and IL-6 at different aspects.

Animals↗