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Biomedical subjects

Pei Wang

Publications and source records attributed to Pei Wang.

At least 37 records · Page 2Linked to original sources
PubMed2006

[Study on the mechanism of alleviation of myocardial injury after early escharectomy en masse of several burns in rat].

OBJECTIVE: To investigate the alleviation of myocardial injury of rats after early escharectomy en masse of severe burns, and to explore its molecular mechanism. METHODS: Totally 66 SD rats were randomly divided into normal control (n=6), non-escharectomy (NE, n=30) and escharectomy (E, n=30, with total escharectomy 20 minutes after burns ) groups. The rats in the NE and E groups were inflicted with 30% TBSA full-thickness scald. The content of ATP in mitochondria, troponin I (Tn I) in serum and 4.8-kb deletion of myocardial mitochondrial DNA (mtDNA) of the rats in each group were determined at 1, 3, 6, 12 and 24 post-scald hours (PSH). RESULTS: (1) The content of ATP in myocardial mitochondria was decreased in both E and NE groups, but it was obviously increased at 1 and 6 PSH (0.90 +/- 0.27 microg/mg 0.66 +/- 0.19 microg/mg) in E group when compared with those in NE group (0.74 +/- 0.18 microg/mg, 0.46 +/- 0.21 microg/mg, P < 0.05). (2) There was no obvious change in the serum content of Tn I in E group at 1 and 3 PSH, but the respective content in 1, 3 and 6 PSH was markedly lower than those in NE group (P < 0.05). (3) The 4.8 kb deletion of myocardial mtDNA was found at 1, 3, 24 PSH in NE group, while it was observed only at 1, 12 PSH in E group. The partial and whole deletion rate in E group was lower than that in NE group. CONCLUSION: Early escharectomy en masse can significantly alleviate the myocardial injury after burns,which might be related to its effect in lowering the deletion rate of myocardial mtDNA at early postburn stage.

Adenosine Triphosphate↗
PubMed2006

Normalization regarding non-random missing values in high-throughput mass spectrometry data.

We propose a two-step normalization procedure for high-throughput mass spectrometry (MS) data, which is a necessary step in biomarker clustering or classification. First, a global normalization step is used to remove sources of systematic variation between MS profiles due to, for instance, varying amounts of sample degradation over time. A probability model is then used to investigate the intensity-dependent missing events and provides possible substitutions for the missing values. We illustrate the performance of the method with a LC-MS data set of synthetic protein mixtures.

Chromatography, Liquid↗
PubMed2006

[Transfection and identification of the cloned strain that stably expressing glucagon like peptide-2 receptor in CaCO2 cell lines].

OBJECTIVE: To establish Caco2 cell line with stable expression of glucagon like peptide-2 receptor( GLP-2R) , in order to establish an in vitro model for the study of protective mechanism of GLP-2 of the intestinal tract. METHODS: The GLP-2R/pcDNA3. 1 ( + ) plasmid was verified by restriction endonuclease and sequencing , and then it was transfected into Caco2 cells with lipofectamine. After G418 selection, the clones with stable expression of GLP-2R were obtained by limited dilution cloning and expanding. The mRNA and protein expression of GLP-2R in normal human intestine, Caco2 cells, HER293, VE cells, as well as in transfected Caco2 cells were determined with RT-PCR and Western blot. RESULTS: The sequence of GLP-2R/pcDNA 3. 1 plasmid was correct. No expression of GLP-2R mRNA and protein was found in HER293 and VE cells, but weak expression were found in Caco2 cells, and strong expression was found in normal human intestines. The expression of GLP-2R mRNA and protein expression in Caco2/GLP-2R ( + ) cells were obviously increased after transfection. CONCLUSION: GLP-2R has special distribution. The expression of GLP-2R is weak in normal Caco2 cells. The establishment of Caco2/GLP-2R ( + ) cellular model is beneficial for the further research of the mechanism of action of GLP-2.

Caco-2 Cells↗
PubMed2005

Regulation of tyrosinase trafficking and processing by presenilins: partial loss of function by familial Alzheimer's disease mutation.

Presenilins (PS) are required for gamma-secretase cleavage of multiple type I membrane proteins including the amyloid precursor protein and Notch and also have been implicated in regulating intracellular protein trafficking and turnover. Using genetic and pharmacological approaches, we reveal here a unique function of PS in the pigmentation of retinal pigment epithelium and epidermal melanocytes. PS deficiency leads to aberrant accumulation of tyrosinase (Tyr)-containing 50-nm post-Golgi vesicles that are normally destined to melanosomes. This trafficking is gamma-secretase-dependent, and abnormal localization of Tyr in the absence of PS is accompanied by the simultaneous accumulation of its C-terminal fragment. Furthermore, we show that the PS1M146V familial Alzheimer's disease mutation exhibits a partial loss-of-function in pigment synthesis. Our results identify Tyr and related proteins as physiological substrates of PS and link gamma-secretase activity with intracellular protein transport.

Alzheimer Disease↗
PubMed2005

Genome-wide characterization of gene expression variations and DNA copy number changes in prostate cancer cell lines.

BACKGROUND: The aim of this study was to characterize gene expression and DNA copy number profiles in androgen sensitive (AS) and androgen insensitive (AI) prostate cancer cell lines on a genome-wide scale. METHODS: Gene expression profiles and DNA copy number changes were examined using DNA microarrays in eight commonly used prostate cancer cell lines. Chromosomal regions with DNA copy number changes were identified using cluster along chromosome (CLAC). RESULTS: There were discrete differences in gene expression patterns between AS and AI cells that were not limited to androgen-responsive genes. AI cells displayed more DNA copy number changes, especially amplifications, than AS cells. The gene expression profiles of cell lines showed limited similarities to prostate tumors harvested at surgery. CONCLUSIONS: AS and AI cell lines are different in their transcriptional programs and degree of DNA copy number alterations. This dataset provides a context for the use of prostate cancer cell lines as models for clinical cancers.

Cell Line, Tumor↗
PubMed2005

[Expression of matrix metalloproteinase-9 in renal tissues of rats with chronic allograft nephropathy at early stage and the role thereof].

OBJECTIVE: To investigate the expression of matrix metalloproteinase-9 (MMP-9) in the renal tissues of rats with chronic allograft nephropathy (CAN) at early stage and its role in CAN. METHODS: Orthotopic transplantation of left kidney was performed between 10 male LEW rats and 10 male F344 rats with the formers as recipients. Small dose cyclosporin A was used to suppress acute rejection. Ten days after the operation the right kidneys of the recipients were resected. Ten LEW rats and 10 F344 rats with their single kidneys resected were used as controls. Twelve weeks after the operation the rats were harvested to take out the transplanted kidneys to undergo histologic examination. Immunochemistry was used to examine the expression of MMP-9 protein and transforming growth factor (TGF)-beta1 . RT-PCR was used to examine the expression of MMP-mRNA in the kidney tissues. At the same time 24 h urine samples were collected to examine the urinary protein. The relationship between the expression of MMP-9 and TGF-beta1 and the quantity of SMCs and mononuclear cells. RESULTS: The 24 h urinary protein level of the experimental group was not significantly different from those of the F3244 control group and LEW control group. The serum inosine level of the experimental group was significantly higher than that of the F334 control group and was not significantly different from that of the LEW control group. The degrees of pathologic change degree (Banff score) and fibrosis of kidney interstitium, and the number of inflammatory cells infiltrating into tubulointerstitium, arterial smooth muscle cells (SMCs) in renal cortex, and SMCs in vascular wall of the experimental group were all significantly higher than those of the 2 control groups. The expressions of MMP-9 protein and TGF-beta1 in the kidney interstitium and vascular wall and the expression of MMP-9 mRNA were all significantly higher than those of the 2 control groups. The expression of MMP-9 mRNA in kidney tissues was positively correlated with the degree of infiltration of interstitial mononuclear cells. The MMP-9 mRNA expression level was positively correlated with the number of interstitial mononuclear cells. The MMP-9 protein expression level was positively correlated with the TGF-beta1 expression level in the tubulointerstitium and in the renal arterial wall. CONCLUSION: MMP-9 plays a key role in CAN at early stage. Its expression may be induced by TGF-beta1.

Animals↗
PubMed2005

Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2.

Biochemical and genetic studies place the amyloid precursor protein (APP) at the center stage of Alzheimer's disease (AD) pathogenesis. Although mutations in the APP gene lead to dominant inheritance of familial AD, the normal function of APP remains elusive. Here, we report that the APP family of proteins plays an essential role in the development of neuromuscular synapses. Mice deficient in APP and its homolog APP-like protein 2 (APLP2) exhibit aberrant apposition of presynaptic marker proteins with postsynaptic acetylcholine receptors and excessive nerve terminal sprouting. The number of synaptic vesicles at presynaptic terminals is dramatically reduced. These structural abnormalities are accompanied by defective neurotransmitter release and a high incidence of synaptic failure. Our results identify APP/APLP2 as key regulators of structure and function of developing neuromuscular synapses.

Amyloid beta-Protein Precursor↗
PubMed2005

High-resolution gene copy number and expression profiling of human chromosome 22 in ovarian carcinomas.

Previous low-resolution studies of chromosome 22 in ovarian carcinoma have suggested its involvement in the development of the disease. We report a high-resolution analysis of DNA copy number and gene expression of 22q in 18 ovarian carcinomas using a 22q-specific genomic microarray. We identified aberrations in 67% of the studied tumors, which displayed 3 distinct gene copy number profiles. The majority of the cases (11 of 18) demonstrated heterozygous terminal deletions of various sizes, the smallest of which was 3.5 Mb. The second profile, detected in 3 tumors, revealed the coexistence of heterozygous deletions and different patterns of low-copy-number gain that involved the proximal half of 22q. The latter finding has not been reported previously in ovarian carcinoma. One case displayed a continuous deletion encompassing the entire 22q, consistent with monosomy 22. Furthermore, we compared the results with the available data on these tumors by using cDNA microarrays to define the degree of correlation between abnormalities at the DNA level and variation in mRNA expression. By a comparison with the expression data, we were able to identify 21 deleted genes showing low mRNA levels and 12 amplified genes displaying elevated gene expression, several of which play roles in cell cycle control and the induction of apoptosis. Our results indicated significant correlation between DNA copy number aberrations and variation in mRNA expression. We also identified several regions and candidate genes on 22q that should be studied further to determine their role in the development of ovarian cancer.

Adenocarcinoma, Clear Cell↗
PubMed2005

Estimation of individual admixture: analytical and study design considerations.

The genome of an admixed individual represents a mixture of alleles from different ancestries. In the United States, the two largest minority groups, African-Americans and Hispanics, are both admixed. An understanding of the admixture proportion at an individual level (individual admixture, or IA) is valuable for both population geneticists and epidemiologists who conduct case-control association studies in these groups. Here we present an extension of a previously described frequentist (maximum likelihood or ML) approach to estimate individual admixture that allows for uncertainty in ancestral allele frequencies. We compare this approach both to prior partial likelihood based methods as well as more recently described Bayesian MCMC methods. Our full ML method demonstrates increased robustness when compared to an existing partial ML approach. Simulations also suggest that this frequentist estimator achieves similar efficiency, measured by the mean squared error criterion, as Bayesian methods but requires just a fraction of the computational time to produce point estimates, allowing for extensive analysis (e.g., simulations) not possible by Bayesian methods. Our simulation results demonstrate that inclusion of ancestral populations or their surrogates in the analysis is required by any method of IA estimation to obtain reasonable results.

Black or African American↗
PubMed2005

Treatment of spinal cord injury with co-grafts of genetically modified Schwann cells and fetal spinal cord cell suspension in the rat.

Fetal spinal cord cells, Schwann cells and neurotrophins all have the capacity to promote repair of injured spinal cord in animal models. To explore the possibility of using these approaches to treat clinical patients, we have examined whether a combination of these protocols produces functional and anatomical improvement. The spinal cords of adult rats (n=16) were injured with a modified New York University (NYU) device (10 gram.5cm). One week after injury, the injured cords were injected with Dulbecco-modified Eagles Medium (DMEM, control group), or fetal spinal cord cell suspension (FSCS) plus nerve growth factor (NGF) gene-modified Schwann cells (SC) and brain-derived neurotrophic factor (BDNF) gene-modified SC (treatment group). The rats were subjected to BBB (Basso, Beattie, Bresnahan, Exp. Neurol. 139:244, 1996) behavioral tests. Anterograde tracing of corticospinal tract was performed before sacrifice 3 months after the treatment. The results showed that the combination treatment elicited a robust growth of corticospinal axons within and beyond the injury site. A dramatic functional recovery in the treatment group was observed compared with the control group. We conclude that the combination of FSCS with genetically modified Schwann cells over-expressing NGF and BDNF was an effective protocol for the treatment of severe spinal cord injury.

Animals↗
PubMed2005

Clinical and protein metabolic efficacy of glutamine granules-supplemented enteral nutrition in severely burned patients.

As an abundant amino acid in the human body, glutamine has many important metabolic roles that may protect or promote tissue integrity and enhance the immune system. A relative deficiency of glutamine in such patients could compromise recovery and result in prolonged illness and an increase in late mortality. The purpose of this clinical study is to observe the effects of enteral supplement with glutamine granules on protein metabolism in severely burned patients. Forty-eight severe burn patients (total burn surface area 30-75%, full thickness burn area 20-58%) who met the requirements of the protocol joined this double-blind randomized controlled clinical trial. Patients were randomly divided into two groups: burn control group (B group, 23 patients) and glutamine treated group (Gln group, 25 patients). There was isonitrogenous and isocaloric intake in both groups, glutamine and B group patents were supplemented with glutamine granules or placebo (glycine) at 0.5 g/kg per day for 14 days with oral feeding or tube feeding, respectively. The level of plasma glutamine, plasma protein content, urine nitrogen and urine 3-methylhistidine (3-MTH) excretion were determined, wound healing rate of the burned area and hospital stay were recorded. The results showed that there were significant reductions in plasma glutamine level and abnormal protein metabolism. After supplement with glutamine granules for 14 days, the plasma glutamine concentration was significantly higher than that in B group (607.86+/-147.25 micromol/L versus 447.63+/-132.38 micromol/L, P<0.01) and the plasma prealbumin and transferrin in Gln group were remarkably higher than those in B group (P<0.01), but the concentration of total protein and albumin were not significantly changed compared with B group (P>0.05). On the other hand, the amount of urine nitrogen and 3-MTH excreted in Gln group were significantly lower than that in B group. In addition, wound healing was faster and hospital stay days were shorter in Gln group than B group (46.59+/-12.98 days versus 55.68+/-17.36 days, P<0.05). These indicated that supplement glutamine granules with oral feeding or tube feeding could abate the degree of glutamine depletion, promote protein synthesis, inhibit protein decompose, improve wound healing and reduce hospital stay.

Adolescent↗
PubMed2005

A method for calling gains and losses in array CGH data.

Array CGH is a powerful technique for genomic studies of cancer. It enables one to carry out genome-wide screening for regions of genetic alterations, such as chromosome gains and losses, or localized amplifications and deletions. In this paper, we propose a new algorithm 'Cluster along chromosomes' (CLAC) for the analysis of array CGH data. CLAC builds hierarchical clustering-style trees along each chromosome arm (or chromosome), and then selects the 'interesting' clusters by controlling the False Discovery Rate (FDR) at a certain level. In addition, it provides a consensus summary across a set of arrays, as well as an estimate of the corresponding FDR. We illustrate the method using an application of CLAC on a lung cancer microarray CGH data set as well as a BAC array CGH data set of aneuploid cell strains.

Algorithms↗
PubMed2005

Array-based comparative genomic hybridization identifies localized DNA amplifications and homozygous deletions in pancreatic cancer.

Pancreatic cancer, the fourth leading cause of cancer death in the United States, is frequently associated with the amplification and deletion of specific oncogenes and tumor-suppressor genes (TSGs), respectively. To identify such novel alterations and to discover the underlying genes, we performed comparative genomic hybridization on a set of 22 human pancreatic cancer cell lines, using cDNA microarrays measuring approximately 26,000 human genes (thereby providing an average mapping resolution of <60 kb). To define the subset of amplified and deleted genes with correspondingly altered expression, we also profiled mRNA levels in parallel using the same cDNA microarray platform. In total, we identified 14 high-level amplifications (38-4934 kb in size) and 15 homozygous deletions (46-725 kb). We discovered novel localized amplicons, suggesting previously unrecognized candidate oncogenes at 6p21, 7q21 (SMURF1, TRRAP), 11q22 (BIRC2, BIRC3), 12p12, 14q24 (TGFB3), 17q12, and 19q13. Likewise, we identified novel polymerase chain reaction-validated homozygous deletions indicating new candidate TSGs at 6q25, 8p23, 8p22 (TUSC3), 9q33 (TNC, TNFSF15), 10q22, 10q24 (CHUK), 11p15 (DKK3), 16q23, 18q23, 21q22 (PRDM15, ANKRD3), and Xp11. Our findings suggest candidate genes and pathways, which may contribute to the development or progression of pancreatic cancer.

Cell Line, Tumor↗
PubMed2005

[Influence of the enteral feeding of levorotatory arginine on severely burned patients during shock stage].

OBJECTIVE: To investigate the effects and the mechanism of action of postburn dietary supplementation of levorotatory arginine (L-Arg) on burn shock resuscitation in severely burned patients. METHODS: This study was designed to be a prospective, randomized, single blinded and controlled one. Twenty burn patients with total burn surface area (TBSA) more than 30% were enrolled and randomized into two groups; 1) Group A (n = 10): enteral feeding of 50 g/L glucose normal saline (GNS) 500 ml per day containing L-Arg (400 mg/kg.day) at equal pace with fluid infusion for shock resuscitation for 4 days. 2) Group C (n = 10): enteral feeding with only 50 g/L GNS 500 ml per day for 4 days. All of the twenty patients received equal amount of enteral feeding via an intra-gastric tube with the aid of an enteral feeding pump, started within 24 postburn hours (PBH). Venous blood was harvested from all the patients in both groups on 1, 2, 3 and 4 postburn day (PBD) for the determination of serum content of nitric oxide (NO), malondialdehyde (MDA) and the activity of serum superoxide dismutase (SOD). And the arterial content of lactate (BL) was also determined concomitantly. RESULTS: The results indicated that the serum SOD activity in group A was increased after burns, peaked on 4 PBD (68 +/- 23 U/ml), and it was obviously higher than that in group C (31 +/- 9 U/ml, P < 0.01). The serum contents of MDA and NO were decreased in both groups after burns. On 2 PBD, the serum NO level in group A decreased to the lowest level (50 +/- 14 micromol/L), which was obviously lower compared with group C (78 +/- 22 micromol/L, P < 0.01). On 4 PBD, serum MDA levels in group A (3.4 +/- 0.8 micromol/L) and group C (3.5 +/- 1.3 micromol/L) were decreased to the lowest level. The BL content in group A was obviously lower than that in group C on 2 and 3 PBD (P < 0.05 or 0.01). CONCLUSION: Enteral supplementation of L-arginine can decrease excessive NO production to a relatively normal level, and it might be beneficial to resuscitation of burn shock. It might also exert a protective effect against ischemia/reperfusion injury to burn patients.

Adolescent↗
PubMed2005

[Comparative study on the influence of arginine hydrochloride and arginine acetate on the immune function and acid-base balance in rabbits with severe burns].

OBJECTIVE: To investigate the influence of arginine hydrochloride and arginine acetate on the immune function and acid-base balance in rabbits with severe burns. METHODS: One hundred and ten flap-eared rabbits were used in the study, in which 8 served as normal control, while the rest were inflicted with 30% TBSA full thickness burn. All the rabbits were divided into 10 groups, i.e. normal control (C, n = 14), burn control (B, n = 14, with intravenous infusion of Ringer's solution), 0.3 g/kg arginine hydrochloride (AH, n = 12), 0.3 g/kg arginine acetate (AA, n = 10), 0.6 g/kg AH (n = 10), and 0.6g/kg AA (n = 10) groups, 1.2 g/kg AH (n = 10), 1.2 g/kg AA (n = 10), 2.4 g/kg AA (n = 14) and 2.4 g/kg AH (n = 12) groups. AA and AH in different doses were fed to rabbits in corresponding groups 2 times a day for 7 days. The changes in the immune function, acid-base balance, chloride ion metabolism, and mortality were determined. RESULTS: Disorder in immune system was found after severe burns, with enhanced immune function at the beginning and weakening afterwards. The lymphocytic transformation rate, the CD4/CD8 ratio, the phagocytosis rate and the chemotactic index of white blood cells on 7 post burn day (PBD) were obviously lower in B group compared with C group (P < 0.05 or 0.01). These indices were obviously higher in 1.2, 2.4 g/kg AA and AH groups than those in B group on 7 PBD (P < 0.05 or 0.01). There was no difference in improvement of immune functions between 0.3, 0.6g/kg AH, AA group and B group. The values of blood pH, base excess (BE), buffer base (BB), HCO(3)(-) level in AH group were significantly lower than those in C group on 7 PBD (P < 0.05 or 0.01), while there were no obvious changes in AA group, they were obviously higher than those in AH group (P < 0.05 or 0.01). The contents of chloride ion in but 2.4 g/kg AH group during 5 to 7 PBD were obviously higher than those in C group and 2.4 g/kg AA group (P < 0.05 or 0.01), while no difference was found between 2.4 g/kg AA and C groups. The mortality in B group was obviously higher than that in 0.3, 0.6, 1.2 g/kg AH and AA groups (P < 0.05 or 0.01), but significantly lower than that in 2.4 g/kg AA and AH groups (P < 0.05). CONCLUSION: Disorders in immune functions were observed in severely burned rabbits. Administration of arginine acetate as well as arginine hydrochloride could enhance the immune function, but arginine acetate seemed to be safer than arginine hydrochloride. Excessive dosage should be avoided to prevent a rise of the mortality.

Acetates↗
PubMed2005

[Study on five point mutations in mitochondrial DNA in patients with Leber's hereditary optic neuropathy].

OBJECTIVE: To analyze the relationship between the primary mutation at np11778 and the secondary mutations at np9804, np13708, np13730, np15257 in three Chinese pedigrees with Leber's hereditary optic neuropathy (LHON) and to detect the effects of the mutations on LHON. METHODS: Thirty-seven maternal individuals from three LHON pedigrees and forty-seven normal controls were involved in this study. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing were used to detect the mutations in mitochondrial DNA (mtDNA). RESULTS: All patients and their maternal relatives had the np11778 mtDNA primary mutation. None had the secondary mutations at np9804, np13708 and np13730 and np15257. DNA sequencing of the PCR fragment revealed six new point mutations at np13759, np13928, np13942, np15301, np15323 and np15326. CONCLUSION: All three Chinese pedigrees with LHON had the mtDNA11778 primary mutation. The frequency of mutation at np13759 in Chinese patients with LHON is higher than that in normal Chinese controls. These findings indicate that np13759 is a new secondary mutation of LHON in Chinese.

Adolescent↗
PubMed2004

A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms.

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms (SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds (a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines--in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases.

Alleles↗