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Biomedical subjects

G M Xu

Publications and source records attributed to G M Xu.

8 recordsLinked to original sources

Polycystin-1 interacts with intermediate filaments.

Polycystin-1, the protein defective in a majority of patients with autosomal dominant polycystic kidney disease, is a ubiquitously expressed multi-span transmembrane protein of unknown function. Subcellular localization studies found this protein to be a component of various cell junctional complexes and to be associated with the cytoskeleton, but the specificity and nature of such associations are not known. To identify proteins that interact with the polycystin-1 C-tail (P1CT), this segment was used as bait in a yeast two-hybrid screening of a kidney epithelial cell library. The intermediate filament (IF) protein vimentin was identified as a strong polycystin-1-interacting partner. Cytokeratins K8 and K18 and desmin were also found to interact with P1CT. These interactions were mediated by coiled-coil motifs in polycystin-1 and IF proteins. Vimentin, cytokeratins K8 and K18, and desmin also bound directly to P1CT in GST pull-down and in in vitro filament assembly assays. Two observations confirmed these interactions in vivo: (i) a cell membrane-anchored form of recombinant P1CT decorated the IF network and was found to associate with the cytoskeleton in detergent-solubilized cells and (ii) endogenous polycystin-1 distributed with IF at desmosomal junctions. Polycystin-1 may utilize this association for structural, storage, or signaling functions.

Amino Acid Sequence↗

A bacterially expressed peptide prevents experimental infection of primates by the hepatitis E virus.

A 23 kDa peptide of the major structural protein of the hepatitis E virus (HEV) expressed in E. coli was found to naturally interact with one another to form homodimers and the peptide was recognized strongly in its dimeric form by HEV reactive human sera. To determine if the peptide may confer protection against HEV infection, three monkeys were immunized with the purified peptide and three were given placebo. Both groups of animals were challenged with 10(5) genome equivalent dose of the homologous strain of HEV. All control animals excreted the virus for 10-12 days beginning 5 days after the infection. The viral genome was also present in the peripheral blood monocyte (PBMC) samples from two animals, but it was not detected in the plasma samples from any of the animals. The infection in two control animals was accompanied by HEV seroconversion. Immunization was found to abrogate HEV stool excretion in two animals and reduced the viral excretion to one day in the third. None of the immunized animals showed detectable HEV in plasma or PBMC samples nor did the animals showed evidence of HEV seroconversion. These results suggested that immunization with the bacterially expressed peptide may prevent experimental infection of primates with the homologous strain of HEV.

Animals↗

Expression of PDGF and its receptor as well as their relationship to proliferating activity and apoptosis of meningiomas in human meningiomas.

In this study, we detected the expression of platelet-derived growth factor (PDGF) and its receptor in 61 human meningiomas by immunohistochemistry and in situ hybridisation. The results showed that almost all the 61 meningiomas expressed PDGFBB and PDGF beta receptor and the positive rate of PDGFAA was 49%. Only two meningiomas expressed PDGF alpha receptor. The positive rate and the immunostaining intensity of PDGFBB and PDGF beta receptor were higher in atypical meningiomas than in benign types. There was no significant difference between the different types of benign meningiomas. The expression of PDGFB chain mRNA was coincident with that of PDGFB chain protein. There was no correlation between the expression of PDGFAA and the types or grades of meningiomas. The correlation between overexpression of PDGFBB/R beta and tumour grade provides a useful parameter in evaluating the prognosis of patients with meningiomas. The proliferative activity of meningiomas was evaluated by the proliferating cell nuclear antigen labelling index (PCNA LI). In the 61 meningiomas, the average PCNA LI (%) was 1.8+/-1.3, 1.9+/-1.3, 1.7+/-0.8 and 11.6+/-5.3 (in fibrous, meningothelial, transitional and atypical meningiomas, respectively). Statistic analysis shows that the PCNA LI is higher in atypical meningiomas than that in benign types, and there was no significant difference between the different types of benign meningiomas. The expression of PDGFBB and PDGF beta receptor was significant enhanced in ascending order from low PCNA LI meningiomas to high ones. This result suggested that PDGFBB/R beta autocrine loop may stimulate the growth of meningiomas. In this study, we also detected the cell apoptosis of meningiomas by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) method. The average apoptosis labelling index (%) was 0.11+/-0.05, 0.08+/-0.04, 0.09+/-0.03 and 0.35+/-0.15 in fibrous, meningothelial, transitional and atypical meningiomas respectively. The apoptosis labelling index was higher in atypical meningiomas than that in benign types. There was a positive correlation between the apoptosis labelling index and PC NA LI of meningioma. When the positive rate of PDGFBB and/or PDGF beta receptor was higher in meningioma, the apoptotic cells was also increased. In conclusion, the overexpression of PDGFBB and its relevant receptor PDGFR beta in meningiomas was correlated with grade of meningiomas and the proliferative activity of meningiomas; PDGFBB/R beta autocrine loop may play an critical role in the pathogenesis of meningiomas.

Adult↗

Expression of matrix metalloproteinases and the tissue inhibitors of metalloproteinases and their local invasiveness and metastasis in Chinese human pancreatic cancer.

BACKGROUND AND OBJECTIVES: The objective was to evaluate the potent role of matrix metalloproteinases(MMPs) and the tissue inhibitors of metalloproteinases(TIMPs) in processes leading to metastasis and local invasiveness of Chinese human ductal adenocarcinomas of the pancreas. We also evaluated a possible biological association between the gene expression and clinical manifestations. METHODS: Northern blot and in situ hybridization have shown MMP and TIMP gene expression in the pancreas and alterations associated with neoplastic transformation. Fifteen cases of surgical pancreatic specimens were examined, using cDNA probes to MMP2, MMP9, and TIMP1. Findings were correlated with the size of tumor section, CA19-9, pathological classification, thrombosis, and infiltration of capsule and lymphonoids. RESULTS: Increased levels of the mRNA of MMP2, MMP9, and TIMP1 genes, MMP2 approximately MMP9<TIMP1, were found in pancreatic cancer tissues examined. Low levels of transcripts for MMP2, MMP9, and TIMP1 were detectable in pancreata of organ donors. Transcripts coding for MMP2, MMP9, and TIMP1 were found in both stroma and tumor cells. However, gene expression of MMP2, MMP9, and TIMP1 has shown an obvious correlation with the infiltration of capsule cells, surrounding lymphonoids and specific histopathological features. CONCLUSIONS: We concluded that the imbalance between MMPs and TIMPs may help physicians to assess the metastatic potential and then tell the prognosis of individual patients.

Carcinoma, Ductal, Breast↗

The diagnostic value of transendoscopic miniature ultrasonic probe for esophageal diseases.

BACKGROUND AND STUDY AIMS: To investigate the value of a transendoscopic miniature ultrasonic probe (USP) in the diagnosis of esophageal diseases. PATIENTS AND METHODS: Endoscopic ultrasonography was performed by means of USP in 53 patients with esophageal diseases, including 16 with esophageal leiomyoma, 14 with esophageal carcinoma, seven with achalasia, seven with reflux esophagitis, six with esophageal polyps and three with esophageal varices. RESULTS: USP clearly showed all 16 esophageal leiomyomas, whereas, conventional EUS could not show five small leiomyomas less than 1.0 x 1.0 cm in size. The appearance of esophageal leiomyoma was that of a hypoechoic mass with a homogeneous inner echogram arising from the fourth hypoechoic layer. All 14 patients with esophageal carcinoma underwent full endosonographic T and N staging with USP. In two cases passage of the malignant stenosis proved to be impossible using conventional EUS. The accuracy of USP on T staging and N staging was 80% and 30%, respectively. In the seven achalasia patients USP demonstrated a seven-layer structure of the esophageal wall, with thickening of the third and fifth layers. In the seven patients with reflux esophagitis no difference was found for the ultrasonic image between that with and that without Barrett's epithelium. All of the esophageal polyps were showed by USP as hypoechoic homogeneous lesion with indistinct margins. After endoscopic sclerotherapy the ultrasonographic feature of esophageal varices changed from submucosal multiple anechoic areas to high echoic areas. CONCLUSION: With refinement, the transendoscopic miniature ultrasonic probe will play an increasing role in the diagnosis of esophageal disease.

Endosonography↗

[Detection of north-Asia tick-borne spotted fever in ticks and rodents along the Heilongjiang river-side by restriction fragment length polymorphism of PCR products].

In order to elucidate the natural foci of North-Asia tick-borne spotted fever along the bank of Heilongjiang river, we used PCR/RFLP to detect spotted fever group rickettsiae in ticks and rodents. The results showed that the wild samples of Dermacentor silvarum, Haemaphysalis concinna and Apodemus agrarius, Microtus fortis, Clethrionomys rufocanus and Ondatra zibethica were all positive with amplification, but typhus rickettsiae, tsutsugamushi fever rickettsiae and Q fever rickettsiae were all negative. Futher RFLP analysis of amplified products with PstI and Rsal demonstrated that their restriction endonuclease profiles were identical to Rickettsia sibirica, but were different from the other prototype strains of SFG rickettsiae, suggesting the possible existance of natural foci of North-Asia tick borne spotted fever in these areas.

Animals↗