Biomedical subjects

Xiangdong Wang

Publications and source records attributed to Xiangdong Wang.

45 records · Page 3Linked to original sources

PubMed2002

Effective treatment of gut barrier dysfunction using an antioxidant, a PAF inhibitor, and monoclonal antibodies against the adhesion molecule PECAM-1.

BACKGROUND: Oxygen free radicals (OFRs), platelet activating factor (PAF), cell adhesion molecules, and transmigration of polymorphonuclear leukocytes through the gut barrier are probably all essential in the development of gut barrier dysfunction following intestinal ischemia and reperfusion (I/R). Pretreatment and early treatment of I/R with the OFRs-scavenger (NAC), the PAF inhibitor lexipafant, and monoclonal antibodies against the adhesion molecule PECAM-1 (anti-PECAM-1-Mab) have been reported to be effective in the prevention or recovery of gut barrier dysfunction and result in a decrease in cytokine levels. Less is known about the effect of treatment inserted during the late stage of I/R. The objective of this study was to evaluate the potential therapeutic value of single or combination therapy with NAC, lexipafant, and anti-PECAM-1-MAb administered late during intestinal I/R in the rat. METHODS: NAC, lexipafant, and anti-PECAM-1-MAb were administrated, alone or in combination, after 3 h of reperfusion following 40 min of superior mesenteric arterial ischemia in the rat. Intestinal endothelial and epithelial barrier permeability, myeloperoxidase (MPO) activity, interleukin-1 beta (IL-1 beta), and protease inhibitor levels were evaluated after 12 h of reperfusion. RESULTS: Intestinal endothelial and epithelial permeability significantly increased in rats with I/R and saline treatment. Proteolytic activity in plasma was indicated by low levels of the three measured plasma protease inhibitors. Intestinal mucosal MPO content increased significantly. These changes were, to different degrees, reduced by late inserted treatment with NAC, lexipafant, or anti-PECAM-1-MAb. Alterations in systemic levels of IL-1 beta paralleled the changes found in gut barrier permeability and leukocyte trapping. Systemic antithrombin III levels and increased barrier permeability in remote organs were partly restored, especially by multimodal therapy. CONCLUSION: Treatment with NAC, lexipafant, and/or monoclonal antibodies against PECAM-1, inserted at a later stage of I/R, reduced the severity of I/R-associated intestinal dysfunction and decreased the systemic concentrations of IL-1 beta, local leukocyte recruitment (MPO), and partly restored plasma protease inhibitor levels.

Animals↗

PubMed2002

Human adrenocortical cell xenotransplantation: model of cotransplantation of human adrenocortical cells and 3T3 cells in scid mice to form vascularized functional tissue and prevent adrenal insufficiency.

To establish an experimental model for replacement of endocrine organ function by xenotransplantation, human adrenocortical cells from postnatal donors were transplanted beneath the kidney capsule of adrenalectomized scidmice together with mitomycin C-treated 3T3 cells that secrete FGF. Adrenocortical cells from seven donors, male and female, ranging from 6-50 years of age, were used. 12 of 13 animals survived > 16 days following surgery. After 50 days they were sacrified to allow assessment of the histology and ultrastructure of tissue formed from the transplanted cells. Only 1 of 23 adrenalectomized sham-operated animals survived > 16 days. In all surviving animals, vascularized adrenocortical tissue formed at the site of transplantation. Cortisol, the normal human glucocorticoid, was present in the plasma of these animals, replacing corticosterone, the mouse glucocorticoid. Some animals, but not most, had measurable aldosterone. The tissue formed from the transplanted cells showed histological and ultrastructural features of normal adrenal cortex. Mitochondria had tubulo-vesicular cristae and there were prominent microvilli between cells. Tissues had a well-developed vasculature, sometimes with large sinusoidal vessels. Proliferation in the transplant tissues was very low. These results show that tissue formed from transplanted human adrenocortical cells is able to replace the essential functions of the adrenal gland in scid mice. This demonstrates that transplanted human endocrine cells can functionally replace a surgically removed endocrine organ in a host animal.

3T3 Cells↗

PubMed2002

Mast cells contribute to early pancreatitis-induced systemic endothelial barrier dysfunction.

BACKGROUND: Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiological process of acute conditions. The aim of the study was to evaluate the effect of mast cell stimulation on the early development of multiple organ dysfunction (MODS) in acute pancreatitis (AP). METHODS: AP was induced by the intraductal infusion of 5% sodium taurodeoxycholate in the rat. Tissue endothelial barrier dysfunction (TEBD) was measured by plasma exudation of radiolabeled albumin. Activation of mast cells was estimated by measuring the release of histamine. Mast cell stimulation was achieved with compound 48/80 (C48/80) administered intravenously (i.v.) or intraperitoneally (i.p.) in different doses either as pretreatment (30 min prior to induction of AP) or treatment immediately after induction of AP. RESULTS: Administration of C48/80 both i.p. and i.v. demonstrated the same effects. A single pretreatment dose of C48/80 (0.5 mg/kg) significantly reduced AP-induced TEBD in the pancreas and gut. Administration of C48/80 immediately after sham operation or induction of AP resulted in a significant increase in pancreatic and intestinal TEBD (p < 0.05 vs. AP+saline). Plasma levels of histamine increased with increasing doses of C48/80. CONCLUSION: The results imply that mast cell activation could be involved in the initiation of AP and the early phase of AP-induced MODS. Mechanisms seem to be complex and are still to be elucidated.

Acute Disease↗

PubMed2002

A role for Grb2-associated binder-1 in growth hormone signaling.

GH signaling begins with activation of the GH receptor (GHR)-associated cytoplasmic tyrosine kinase, Janus kinase-2. GH-induced Janus kinase-2 activation leads to engagement of several signaling pathways, including the extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase, phosphoinositol 3-kinase, and signal transducer and activator of transcription-5 (STAT5) pathways. Previous work suggests that ERK activation in response to GH may be modulated by several proteins acting as docking molecules, including the epidermal growth factor receptor (EGFR) and insulin receptor substrate-1. In this study we investigate potential roles for the pleckstrin homology (PH) domain-containing insulin receptor substrate-like protein, Grb-2-associated binder-1 (Gab1), in GH signaling. We find in 3T3-F442A preadipocytes that GH promotes tyrosine phosphorylation of Gab1 and its association with SHP2, an Src homology 2-containing cytoplasmic tyrosine phosphatase. The Grb2 adapter protein, in contrast, is specifically coimmunoprecipitated with Gab1, even in the absence of GH exposure. Using a COS-7 cell transient reconstitution system, we observed that GH-induced Gab1 tyrosine phosphorylation is dependent on the Gab1 PH domain, whereas GH-induced coimmunoprecipitation of SHP2 requires tyrosine 627 of Gab1, as previously reported for EGF-induced Gab1-SHP2 association. Deletion of the Gab1 PH domain significantly attenuates GH-induced ERK activation and trans-activation of a c-fos enhancer-driven reporter construct compared with wild-type Gab1 in this system. In contrast, GH-induced STAT5 tyrosine phosphorylation and STAT5-dependent trans-activation are similar in cells expressing wild-type or PH domain-deleted Gab1. Notably, neither the ERK nor the STAT5 GH-dependent signaling outcome is affected by expression of the Gab1 mutant with tyrosine 627 changed to phenylalanine. Finally, we observed GH-dependent translocation of a wild-type, but not a PH domain-deleted, Gab1-green fluorescent protein chimera from the cytoplasm to the plasma membrane. Our results suggest selective involvement of Gab1 in GH-induced ERK activation and implicate the Gab1 PH domain as critical in this involvement.

3T3 Cells↗

PubMed2002

[Application of endoscopic ultrasonography in the diagnosis of mediastinal lymph node metastasis].

OBJECTIVES: To calculate the rate of detection for mediastinal lymph nodes and to set up a criteria for the diagnosis of metastatic mediastinal lymph nodes in lung neoplasm by means of endoscopic ultrasonography (EUS). METHODS: In 21 patients with lung cancer who underwent preoperative EUS on mediastinal lymph nodes, 103 lymph nodes detected by EUS were resected and confirmed pathologically all. The difference between benign and malignant lymph nodes was analysed statistically. RESULTS: The rates of metastatic lymph nodes detected by EUS were significantly higher than these of non-metastatic lymph nodes (chi(2) = 11.752, P = 0.01) in levels 5, 7, 8, and 9 of mediastinal lymph node staging map (Union Internationale Contre le Cancer, 1997). The mean long and short axis of metastatic lymph nodes were significantly longer than those of non-metastatic lymph nodes (short axis: t = 4.541, P = 0.000; long axis: t = 3.278, P = 0.002). Metastatic lymph nodes showed some characteristic ultrasonographic features, including short axis >/= 1.0 cm, long axis >/= 1.5 cm, and clear boundary. According to the equation P((1)) = 1/[1 + e(-(-2.963 + 2.041 X1 + 1.681 X2))], the lymph nodes were assumed to be malignant when P((1)) >/= 0.5. The accuracy, sensitivity, specificity of this methods were 72.8%, 72.7%, 72.9% respectively, and were superior to those of CT for the same nods in levels 5, 7, 8 and 9 (chi(2) = 6.812, P = 0.013). CONCLUSION: EUS is an effective method of diagnostic evaluation of mediastinal lymph nodes of lung cancer.

Adult↗

PubMed2002

[Endoscopic ultrasonography guided fine-needle aspiration in diagnosis of lung neoplasm and mediastinal lymph node metastasis].

OBJECTIVE: To access the feasibility, safety and accuracy of endoscopic ultrasonography guided fine-needle aspiration (EUS-FNA) in patients with suspected lung neoplasm and metastatic mediastinal lymph nodes. METHODS: Using a linear array scanning endosonography (Pentax FG32-UA) and a 22-guage GIP (Medi-Globe) needle, we performed EUS-FNA in 10 patients including 6 patients with lung mass and enlarged mediastinal lymph nodes, 1 patient with a mass in the right lung, 1 patient with a mass near the esophagus, and 2 patients with extensive enlarged mediastinal lymph nodes. The data collected included lesions types, complications and diagnostic accuracy. RESULTS: EUS-FNA revealed small cell carcinoma in 5 patients, squamous cell carcinoma in 1, adenocarcinoma in 1, and benign lymph nodes in 2. Malignancy was confirmed by follow-up in 7 patients, and benign tumor was confirmed by mediastinoscopy, thoracoscopy or follow-up in 2 patients. In 1 patient, FNA sample was not diagnosed because of inadequate specimen. None of the patients had complications caused by any procedures. CONCLUSION: EUS-FNA is safe, reliable and accurate in diagnosis of suspicious lung neoplasm and mediastinal lymph node.

Adult↗

PubMedDate not supplied

Alterations of adhesion molecule expression and inflammatory mediators in acute lung injury induced by septic and non-septic challenges.

The lung is frequently the first failing organ during the sequential development of multiple organ dysfunction under both septic or non-septic conditions. The present study compared polymorphisms of tumor necrosis factor (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), and adhesion molecule (AM) expression on circulating, recruited, and migrating leukocytes in the development of lung injury after induction of acute pancreatitis (AP) or abdominal sepsis by cecal ligation and puncture (CLP). Pulmonary alveolar barrier and endothelial barrier permeability dysfunction were measured. The expression of AMs (CD11b, CD11b/c, CD31, CD54 and CD62L) on leukocytes isolated from blood, lung tissue, and bronchoalveolar space were measured by flowcytometry. Plasma exudation to the interstitial tissue and the bronchoalveolar space significantly increased 1 and 3 hours after induction of pancreatitis and to the bronchoalveolar space from 6 hours after sepsis. Bronchoalveolar levels of MCP-1 significantly increased earlier than plasma exudation to the alveoli in both pancreatitis and sepsis. Alterations in expression of adhesion molecules on bronchoalveolar lavage (BAL) leukocytes can represent a marker reflecting leukocyte activation in the lung tissue, since both BAL and lung tissue leukocytes showed similar patterns of changes. Expression of adhesion molecules on circulating leukocytes increased 1 hour after induction of pancreatitis. Activating phenotypes of circulating, lung tissue and bronchoalveolar leukocytes may thus be responsible for the-development and severity of secondary lung injury.

Acute Disease↗

PubMedDate not supplied

Influence of mast cells on the expression of adhesion molecules on circulating and migrating leukocytes in acute pancreatitis-associated lung injury.

Pancreatitis-associated lung injury is an early-occurring and severe complication, still associated with substantial mortality. A number of inflammatory cells and their products are involved in the initiation and progress of the condition. In the present study, acute pancreatitis (AP) was induced by the intraductal infusion of 5% sodium taurodeoxycholate in the rat. Pulmonary endothelial barrier dysfunction was measured by plasma exudation of radiolabeled albumin. Expression of PECAM-1, ICAM-1, and L: -selectin on neutrophils (CD11b(+)) and monocytes/macrophages (CD11b/c(+)), obtained from circulation and lung tissue, was measured 1 and 6 hours after AP induction (n = 10 rats/time point/group). Plasma levels of histamine and serotonin were determined. The role of mast cells was evaluated by pretreatment with the mast cell stabilizer cromolyn. Intraperitoneal administration of cromolyn downregulated pancreatitis-induced systemic increase of histamine at 1 hour (513 +/- 82 vs. 309 +/- 50, p < 0.05). Cromolyn prevented a decreased expression of PECAM-1 on circulatory neutrophils and monocytes/macrophages and against an increased expression of ICAM-1 and PECAM-1 on pulmonary neutrophils and monocytes/macrophages 6 hours after AP induction (about 40% vs. 10%, p < 0.01). The mast cell stabilizer also prevented pancreatitis-induced pulmonary endothelial barrier dysfunction at 6 hours. Thus, our data indicate that mast cells may play a critical role in the activation of leukocytes during the initiation of pancreatitis-associated lung injury by altering phenotypes of adhesion molecules.

Acute Disease↗

PubMedDate not supplied

Proteomics and leukocytes: an approach to understanding potential molecular mechanisms of inflammatory responses.

Leukocytes play an important role in the progression of disease and leukocyte-derived proteins are associated with the pathogenesis of the disease. Leukocyte activation causes production of inflammatory mediators, over-expression of cell surface adhesion molecules, and an increase in migration and infiltration, phagocytosis, and degranulation, as well as receptor phosphorylation and signal transduction. An increasing number of studies on the application of leukocyte proteomics have appeared in mapping protein profiles of inflammatory cells, contributing to the understanding of potential mechanisms involved in leukocyte function. Together with improvements in proteomic technology in leukocyte research, leukocyte proteomic analysis becomes more simple, rapid, flexible, sensitive, and specific. This enables proteomic investigation of activated or non-activated leukocytes to be highly focused on defined suborgans or specific signaling pathways. Research in leukocyte proteomics is progressing from fingerprinting to functioning, human cell lines to primary leukocytes, non-activated cells to inflammatory mediator-stimulated cells, in vitro culture to in vivo challenge, and animal models to human disease. A number of newly identified proteins from leukocyte proteomics may offer new mechanism-orientated targets for drug discovery and development.

Dendritic Cells↗