Biomedical subjects

Ping Hou

Publications and source records attributed to Ping Hou.

13 recordsLinked to original sources

PubMed2007

Dynamic contrast-enhanced MRI study of male pelvic perfusion at 3T: preliminary clinical report.

PURPOSE: To detect male pelvic perfusion in patients with coronary artery disease (CAD) vs. controls by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at 3T. MATERIALS AND METHODS: Eighteen male patients were studied with T1-weighted (T1W) DCE-MRI to measure perfusion, phase-contrast (PC) imaging to measure bulk flow, and contrast-enhanced (CE)-MRA to detect stenosis. Regions of interest (ROIs) in prostate, corpus cavernosal, and spongiosal tissues were analyzed. Two-compartment pharmacokinetic modeling was employed to fit the signal enhancement. Perfusion parameters were analyzed by curve-fitting and utilized to compare the CAD and control groups. Validated questionnaires measuring urinary and erectile function were used to evaluate pelvic symptomatology in both groups. RESULTS: Mean perfusion analysis confirmed weaker and slower enhancement in CAD patients vs. controls despite equivalent cardiac output values. The mean maximum enhancement was 26.33 +/- 0.12 (controls) vs. 22.38 +/- 0.44 (CAD) for prostate. The mean wash-in rate in units of minute(-1) was 62.10 +/- 1.74 (controls) vs. 34.44 +/- 1.08 (CAD) for prostate, 16.68 +/- 0.72 (controls) vs. 8.04 +/- 0.36 (CAD) for spongiosal, and 8.34 +/- 0.54 (controls) vs. 3.48 +/- 0.24 (CAD) for cavernosal tissues (all with P < 0.0001). CONCLUSION: This preliminary study demonstrates that perfusion parameters differ between CAD and control patients, and the findings mirror the differences in pelvic symptoms in these groups.

Aged↗

PubMed2006

Tandem repeats polymorphism of MUC20 is an independent factor for the progression of immunoglobulin A nephropathy.

MUC20, an upregulated novel gene in the renal tissues of patients with IgA nephropathy (IgAN), was recently identified. The variable number of tandem repeats (VNTR) polymorphism of the MUC20 gene was detected in several cell lines. In the present study, we investigated a possible association of MUC20 VNTR polymorphism with the clinical manifestations and progression in patients with IgAN. A total of 1,147 Chinese subjects, including 657 patients with IgAN and 490 geographically matched healthy controls, were involved in this investigation. One hundred and thirty-seven patients had been followed up for 60.6 +/- 22.4 months. MUC20 VNTR polymorphism was genotyped by polymerase chain reaction amplification and confirmed by sequencing. The alleles were divided into two groups according to the repeat times of MUC20 VNTR, i.e. small alleles (VNTR repeat times < or = 3) and large alleles (VNTR repeat times >3), and the genotypes of subjects were classified into SS, SL and LL groups. The frequencies of the alleles and genotypes of MUC20 VNTR polymorphisms did not differ between patients with IgAN and healthy controls. Additionally, there was no significant difference in the clinical features. Furthermore, IgAN patients with SL/LL genotypes had a higher risk of decline in renal function (odds ratio 20.9; 95% confidence interval 2.6-168.1; p = 0.004) than those with SS genotypes. The present study revealed that there is no association between the VNTR polymorphism of the MUC20 gene and the clinical manifestations in IgAN patients at the time of renal biopsy. However, IgAN patients with SL/LL genotypes had a higher risk of the progression to end-stage renal disease.

Adolescent↗

PubMed2006

B cell antigen receptor signaling and internalization are mutually exclusive events.

Engagement of the B cell antigen receptor initiates two concurrent processes, signaling and receptor internalization. While both are required for normal humoral immune responses, the relationship between these two processes is unknown. Herein, we demonstrate that following receptor ligation, a small subpopulation of B cell antigen receptors are inductively phosphorylated and selectively retained at the cell surface where they can serve as scaffolds for the assembly of signaling molecules. In contrast, the larger population of non-phosphorylated receptors is rapidly endocytosed. Each receptor can undergo only one of two mutually exclusive fates because the tyrosine-based motifs that mediate signaling when phosphorylated mediate internalization when not phosphorylated. Mathematical modeling indicates that the observed competition between receptor phosphorylation and internalization enhances signaling responses to low avidity ligands.

Amino Acid Motifs↗

PubMed2005

Spi-1 and Spi-B control the expression of the Grap2 gene in B cells.

The Ets family members Spi-1 and Spi-B have been implicated in the regulation of genes important for B cell antigen receptor (BCR) signaling. Mice deficient in Spi-B exhibit reduced B cell proliferation in response to BCR cross-linking and impaired T cell-dependent immune responses. This defect is exacerbated in the presence of Spi-1 haplo-insufficiency (Spi1+/- SpiB-/-). Tyrosine phosphorylation and calcium mobilization induced by BCR engagement is diminished in Spi1+/- SpiB-/- B lymphocytes, although many key BCR signaling proteins are expressed, suggesting that Spi-1 and Spi-B regulate expression of additional, unidentified signaling molecules. We now demonstrate that expression of the adaptor protein Grap2 is impaired in Spi1+/- SpiB+/- and Spi1+/- SpiB-/- B lymphocytes. Analysis of two alternate murine Grap2 promoters revealed a functionally important Spi-1 and Spi-B DNA binding element located in the downstream promoter. Ectopic expression of Grap2 in Grap2-deficient B cells reduced the recruitment of BLNK to Igalpha and the phosphorylation of specific substrates. Regulation of BLNK recruitment was dependent upon the Grap2 proline-rich domain, while modulation of phosphorylation was dependent upon both the proline-rich and SH2 domains. These data indicate that Spi-1 and Spi-B directly regulate the expression of Grap2 and that Grap2 functions to modulate BCR signaling, but that reduced Grap2 expression is unlikely to account for the BCR signaling defects observed in Spi1+/- SpiB-/- B cells.

Adaptor Proteins, Signal Transducing↗

PubMed2005

[Variable number of tandem repeats polymorphism of MUC20 is associated with the progression of IgA nephropathy].

OBJECTIVE: The MUC20 gene is a novel up-regulated gene that was identified in renal tissues of patients with IgA nephropathy (IgAN) by restriction endonucleolytic analysis of differentially expressed sequences. The variable number of tandem repeats (VNTR) polymorphism of MUC20 was detected in different cell lines. In this study we determined the distribution of MUC20 VNTR polymorphism in the healthy population, and the association between the MUC20 VNTR polymorphism and the pathogenesis or progression of IgAN. METHODS: 282 healthy and 503 proved IgAN patients by biopsy were involved in this investigation. 113 patients had been followed-up for 3.5 +/- 1.5 years. Genomic DNAs were extracted from peripheral blood leucocytes. MUC20 VNTR polymorphism was detected by PCR amplification and several representational PCR products were confirmed by sequencing. The MUC20 genes were divided into small alleles (repeat times 3) according to the repeat times of MUC20 VNTR. These patients were classified into group SS, SL and LL. MUC20 allele frequencies and genotypes of IgAN patients were analyzed and compared with healthy population. In addition, the associations of MUC20 polymorphism with the clinical and pathological parameters at the time of renal biopsy were analyzed. The data followed up in different groups were compared. RESULTS: There was MUC20 VNTR polymorphism in healthy population with 2 - 6 repeats. The repeat fragment was 57bp. The most frequent alleles included 3(R(3)) and 4(R(4)) repeats; otherwise the least ones included 6(R(6)) repeats. The most frequent genotype was R(3)R(4), then R(3)R(3) and R(4)R(4); the least ones were R(2)R(2), R(3)R(6) and R(5)R(5). The frequencies of MUC20 alleles and genotypes in the IgAN patients were similar to healthy population. Initial ages, blood pressure, proteinuria, and renal function did not differ significantly among the three groups. There was no difference of the urinary osmotic pressure, urinary NAG (N-acetyl-B-D-glucosaminidase) and alpha1 microglobulin (alpha1-MG), and the semiquantitative scores of renal interstitial fibrosis and tubular atrophy in the three groups. IgAN patients with SL/LL genotype had higher odds ratio for progression of renal function (OR = 7.29, 95% CI: 1.68 - 31.60, P = 0.008) than the SS genotype. CONCLUSIONS: There were MUC20 VNTR polymorphisms in the healthy population. The polymorphism did not associate with the pathogenesis and the clinico-pathological parameters at the time of renal biopsy. The SL/LL genotype was likely to be a risk factor for rapid progression of renal function in the patients with IgAN.

Adolescent↗

PubMed2005

Mutation of critical GIRK subunit residues disrupts N- and C-termini association and channel function.

The subfamily of G-protein-linked inwardly rectifying potassium channels (GIRKs) is coupled to G-protein receptors throughout the CNS and in the heart. We used mutational analysis to address the role of a specific hydrophobic region of the GIRK1 subunit. Deletion of the GIRK1 C-terminal residues 330-384, as well as the point mutation I331R, resulted in a decrease in channel function when coexpressed with GIRK4 in oocytes and in COS-7 cells. Surface protein expression of GIRK1 I331R coexpressed with GIRK4 was comparable with wild type, indicating that subunits assemble and are correctly localized to the membrane. Subsequent mutation of homologous residues in both the GIRK4 subunit and Kir2.1 (Gbetagamma-independent inward rectifier) also resulted in a decrease in channel function. Intracellular domain associations resulted in the coimmunoprecipitation of the GIRK1 N and C termini and GIRK4 N and C termini. The point mutation I331R in the GIRK1 C terminus or L337R in the GIRK4 C terminus decreased the association between the N and C termini. Mutation of a GIRK1 N-terminal hydrophobic residue, predicted structurally to interact with the C-terminal domain, also resulted in a decrease in channel function and termini association. We hypothesize that the hydrophobic nature of this GIRK1 subunit region is critical for interaction between adjacent termini and is permissive for channel gating. In addition, the homologous mutation in cytoplasmic domains of Kir2.1 (L330R) did not disrupt association, suggesting that the overall structural integrity of this region is critical for inward rectifier function.

Amino Acid Sequence↗

PubMed2005

Replacement of the membrane proximal region of I-A(d) MHC class II molecule with I-E-derived sequences promotes production of an active and stable soluble heterodimer without altering peptide-binding specificity.

The MHC class II molecule I-A is the murine homologue of HLA-DQ in humans. The I-A and DQ heterodimers display considerable heterodimer instability compared with their I-E and HLA-DR counterparts. This isotype-specific behavior makes the production of soluble I-A and DQ molecules very difficult. We have developed a strategy for production of soluble I-A(d) molecules involving expression of I-A(d) as a glycosil phosphatidyl inositol (PI) anchored chimera in Chinese Hamster Ovary (CHO) cells. The regions comprising the membrane proximal segments of I-A(d) alpha and beta chains were substituted for the corresponding regions of I-E, and the derived constructs were expressed in CHO cells. Procedures for purification of the soluble class II molecules were optimized and the WT and chimeric molecule were compared for structure, biochemical stability and functionality. Our analysis revealed that the substitutions in the membrane proximal domains improved cell surface expression and thermal stability of I-A(d) without altering the peptide binding specificity of the class II molecule. The results suggest that similar strategies could be used to increase the stability of other unstable class II molecules for in vitro studies.

Amino Acid Sequence↗

PubMed2005

[Clinical significance of heparanase and basic fibroblast growth factor expression in human non-small cell lung cancer].

OBJECTIVE: To assess protein and mRNA expression levels of heparanase and basic fibroblast growth factor (bFGF) genes in human non-small cell lung cancer (NSCLC) and their roles in tumor invasion, metastasis and prognosis. METHODS: A total of 115 paraffin-embedded and 45 fresh-frozen tissue specimens of NSCLC were studied by immunohistochemistry, Western Blot and in situ hybridization to evaluate the protein and mRNA expression status of heparanase and bFGF genes. The data was analyzed by SPSS statistical software. RESULTS: Both human heparanase and bFGF were highly expressed in NSCLC cells, in contrast to none or a low expression in normal lung tissue. Expression of heparanase also showed a significantly higher than that in the normal tissue by Western blot (P = 0.041). Immunohistochemistry showed that heparanase expression was both cytoplasmic and membranous. The agreement between heparanase and bFGF was significant. A significant correlation was found between the expression of either protein and TNM stage, vascular invasion, lymphatic metastasis and microvascular density (MVD). Co-expression of the two proteins demonstrated an even higher correlation with the tumor stage and MVD. In addition, expression of bFGF correlated with tumor cell differentiation. Data of a multivariate analysis indicated that tumor cell differentiation, vascular invasion, lymphatic metastasis and expression of bFGF were identified as significant prognostic parameters. CONCLUSIONS: Both heparanase and bFGF may play important roles in tumor angiogenesis, metastasis, and prognosis of NSCLC.

Adult↗

PubMed2004

B-cell antigen receptor signaling requirements for targeting antigen to the MHC class II presentation pathway.

The ability of B lymphocytes to capture, process and present antigens to T cells is requisite for normal humoral immune responses and contributes to the pathogenesis of both B- and T-cell-mediated autoimmune diseases. B lymphocytes preferentially capture polyvalent antigens, which are capable of eliciting a coordinated series of cellular responses that ensure that even low-affinity antigens are productively captured. Polyvalency not only accelerates transit through the endocytic pathway but also induces a reorganization of the antigen-processing compartment, activates degradative pathways and determines how antigenic peptides are presented to T cells. Similar changes are observed in maturing dendritic cells, indicating that some cellular responses to foreign antigens are conserved.

Animals↗

PubMed2004

[Construction of sense and antisense eukaryotic expression vector of novel gene Collectrin and its function in cell growth].

OBJECTIVE: To construct sense and antisense eukaryotic expression vector of novel gene Collectrin and identify its function in cell growth. METHODS: The open reading frame of Collectrin was amplified by PCR and inserted into pcDNA3.1/V5-His plasmid. The recombinant plasmid was identified by restriction enzyme analysis and sequencing analysis. The recombinant plasmid was transfected into M-1 cell by using lipofectin mediation after being identified by restriction enzyme analysis and sequencing analysis. RT-PCR and Western blot were performed to identify the expression of Collectrin. Beta-Gal staining was used to define the effect of transfection. The growth of M-1 cells was examined by MTT and cell counting. RESULTS: Compared with control group, the expression of Collectrin was decreased significantly at both nucleotide and protein levels transfected by antisense vector, but elevated in sense group. The cell growth was blocked after being transfected by antisense plasmid. CONCLUSION: The sense and antisense eukaryotic expression vector of novel gene Collectrin was successfully constructed. Collectrin was one of basic factors in cell growth.

Animals↗

PubMed2003

Screening and identification of the up-regulated genes in human mesangial cells exposed to angiotensin II.

Accumulation of extracellular matrix (ECM) in the glomerular mesangium is a common feature of many progressive renal diseases. Angiotensin II (Ang II) plays a major role in the progression of chronic kidney diseases in part by induction of ECM. However, the precise molecular signals responsible for this effect are unknown. To explore possible molecular mechanisms of ECM production related to Ang II, we screened and identified genes up-regulated by Ang II in cultured human mesangial cells (MC). Detection of up-regulated genes was determined by mRNA populations from human MC with and without Ang II stimulation (10(-6) mol/l, 24 h) by suppression subtractive hybridization. Reverse Northern blot analysis was performed to screen for differentially expressed genes. Full-length cDNAs of three novel genes were isolated by rapid amplification of cDNA ends (RACE)-polymerase chain reaction (PCR). One of these novel genes, AngRem104, was further investigated by Northern blot, Western blot and reverse transcription (RT)-PCR. The bioinformatics analysis implied that AngRem104 coded for a nuclear protein that was widely expressed in various normal human tissues. Moreover, up-regulation of AngRem104 induced by Ang II was time-dependent and was dose-dependently blocked by the Ang II type 1 receptor antagonist, Losartan. Interestingly, we also demonstrated that AngReam104 was associated with increased fibronectin expression. We conclude that AngRem104 is a novel human gene that is related to the expression of fibronectin and that is up-regulated by Ang II in human MC. These findings may lead to new insights into the mechanisms of glomerular sclerosis associated with Ang II.

Amino Acid Sequence↗

PubMed2003

[Screening for proteins interacting with novel gene AngRem104 in the adult human kidney cDNA library by yeast two hybrid system].

OBJECTIVE: To screen for proteins interacting with novel gene AngRem104. METHODS: The yeast strain AH109 was transformed with AngRem104-pGBKT7/c-myc, and yeast-mating was utilized to screen for interacting proteins with AngRem104 in pretransformed human kidney cDNA library. RESULTS: AngRem104 protein was expressed and there was no self-activation and toxicity in AH109. Seven proteins that interacted with AngRem104, including eukaryotic translation elongation factor 1 alpha 1, glucocorticoid receptor AF-1 specific elongation factor, beta 2-microglobulin, BBS2 and four of cell metabolism related proteins, were identified. CONCLUSION: The novel gene AngRem104 may interact with the proteins, which may interfere with cell metabolism, disturb the balance between transcription factors, or may be involved in some immunity related and hereditary diseases. This investigation provides functional clues for further exploration of the novel gene, AngRem104.

DNA, Complementary↗

PubMedDate not supplied

Phase-sensitive T1 inversion recovery imaging: a time-efficient interleaved technique for improved tissue contrast in neuroimaging.

BACKGROUND AND PURPOSE: High tissue contrast and short acquisition time are desirable when scanning patients. The purpose of this report is to describe the implementation of a new technique for generating high gray matter (GM) and white matter (WM) contrast in a short scan time, make a quantitative evaluation of the contrast efficiency, and explore its potential applications in neuroimaging. METHOD: A fully interleaved T1-weighted inversion recovery (T1IR) sequence with phase-sensitive reconstruction (PS-T1IR) is implemented. This sequence is compared with conventional T1-weighted spin-echo imaging (T1SE) and T1-weighted fluid-attenuated inversion recovery (T1FLAIR). The time efficiency and contrast enhancement have been quantitatively analyzed in normal volunteers. The performance of the sequence is evaluated in >30 patients with neurologic disorders. The sensitivity of PS-T1IR relative to T1SE in detecting gadolinium enhancements is also evaluated. RESULTS: PS-T1IR is more time-efficient than T1SE and generates better GM-WM contrast. It results in the best contrast-to-noise ratio (CNR) efficiency (1.16) compared with T1FLAIR (0.73) and T1SE (0.23). For a typical clinical protocol, PS-T1IR takes only 1:30 minutes versus 2:40 minutes for T1SE imaging for the whole brain coverage. Although gadolinium enhancements are detected with comparable sensitivity on both PS-T1IR and T1SE sequences, in certain instances, the latter sequence appears to be more sensitive in demonstrating gadolinium enhancements within WM. CONCLUSION: PS-T1IR has the highest CNR efficiency compared with T1FLAIR and T1SE. It is a very practical technique for neuroradiologic applications.

Brain Diseases↗