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Biomedical subjects

Yan Chen

Publications and source records attributed to Yan Chen.

At least 235 records · Page 13Linked to original sources
PubMed2003

Growth retardation as well as spleen and thymus involution in latent TGF-beta binding protein (Ltbp)-3 null mice.

The latent TGF-beta binding protein (LTBP)-3 is an extracellular matrix (ECM) protein that binds the small latent complex (SLC) of TGF-beta. Disruption of the Ltbp-3 gene by homologous recombination in mice yields mutant animals that display multiple skeletal abnormalities. In addition, these mice have retarded growth. On an inbred 129 SvEv background, half of the Ltbp-3 mutant mice die between 3 and 4 weeks after birth. These mice show severe involution of the thymus and spleen and a sharp reduction in the numbers of CD4/CD8 double positive T-cells in the thymus. The thymus and spleen defect is caused by elevated corticosterone levels in the serum and can be reversed by injection of aminoglutethimide (AMG), an inhibitor of steroid synthesis. This result indicates that the thymus and spleen defect is a secondary defect due to high corticosterone levels probably induced by stress of unknown etiology.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Mutation identification in a 5-generation pedigree with autosomal dominant retinitis pigmentosa.

An extended 5-generation family has been investigated in which 32 of the 111 family members were diagnosed as having retinitis pigmentosa (RP). The proband was a 58-year old male in whom night-blindness was first observed in early childhood, with almost loss of vision by 52 years of age. The symptoms observed in other family members included night-blindness, impaired vision and visual field loss. Dementia, digital abnormalities, deaf-mutism and mental retardation were variously diagnosed in a number of individuals with RP. The affected and unaffected family members were tested for mutations in a range of candidate genes. The 8 exons of three candidate genes have been analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing techniques. A novel mutation was identified in the rhodopsin gene at codon 52 of exon 1 (TTC-TAC) that resulted in a substitution of Phe to Tyr.

DNA Mutational Analysis↗
PubMed2003

The effect of curcumin on mismatch repair (MMR) proteins hMSH2 and hMLH1 after ultraviolet (UV) irradiation on HL-60 cells.

To understand the expression and effect of mismatch repair genes, hMSH2 and hMLH1, and to investigate anti-leukemic cell proliferation mechanism of curcumin, the levels of both genes were detected by multiple comparative RT-PCR. The protein of hMSH2 was determined by flow cytometry (FCM) and the gene mutation of hMSH2 and hMLH1 were detected by PCR-SSCP and microsatellite instability assay. After UV irradiation, the gene expression of hMSH2 and hMLH1 was not increased and showed no response. This phenomenon was not ascribed to gene mutation, because PCP-SSCP and microsatellite instability assay revealed no abnormal gel-shift band in both genes. After irradiation and addition of curcumin, the expression of hMSH2 mRNA increased and the cellular apoptotic rate also increased at the same time. The difference was statistically significant as compared with groups without addition of curcumin and control groups (P < 0.05). Our results suggested that when MMR system was inhibited by the same agents, curcumin can remove this suppression and switch to cellular apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Complete genome sequence of hepatitis B virus (HBV) from a patient with fulminant hepatitis without precore and core promoter mutations: comparison with HBV from a patient with acute hepatitis infected from the same infectious source.

BACKGROUND/AIMS: There is a paucity of information regarding hepatitis B virus (HBV) from patients with fulminant hepatitis (FH) without precore (pre-C, nt 1896) and core promoter (CP, nt 1762, 1764) mutations. METHODS: Pre-C and CP mutations were studied in eight patients with FH and 26 patients with acute hepatitis (AH) due to HBV. One patient with FH (FH1) was infected with HBV without these mutations. Interestingly, the sera of the infectious source (IS1) and of a patient with AH (AH1) infected from IS1 were available. Complete HBV genomes from these three patients were analyzed. RESULTS: These mutations were found in seven of eight FH and five of 26 AH (P<0.01). HBV from FH1, IS1 and AH1 belonged to genotype D. Nucleotide difference between FH1 and AH1 was six of 3182 bases (nt 493, 998, 1173, 2928, 3067, and 3078). Two and five substitutions of deduced amino acid sequences were found in the pre-S1 and polymerase regions, respectively. The same nucleotide substitutions at nt 493, 1173, 2928 and 3067 were found in several patients with FH in our laboratory or GenBank. CONCLUSIONS: These six nucleotide substitutions of HBV DNA could be candidates of mutations relating to FH.

Acute Disease↗
PubMed2003

hnRNP B1 protein may be a possible prognostic factor in squamous cell carcinoma of the lung.

Heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is an RNA-binding protein that is required for the maturation of mRNA precursor. It was previously reported that hnRNP A2/B1 was overexpressed at the early clinical stage of lung cancer, and that hnRNP B1 protein, a splicing variant of hnRNP A2 mRNA, was elevated in lung cancer tissues. In this study, we applied the immunohistochemical method, using anti-hnRNP B1 antibody to analyze the usefulness of the hnRNP B1 antibody as a prognostic marker and also as a marker useful for early detection. A total of 206 specimens were examined. Histological examination revealed this protein to be positive in 79 (71.2%) of 111 squamous cell carcinomas and in 45 (64.3%) of 70 adenocarcinomas, respectively. This protein was also expressed in 24 (63.2%) of 38 roentgenographically occult carcinomas and in seven (63.6%) of 11 dysplastic lesions. These findings suggest the possible participation of this protein in early carcinogenesis. Furthermore, the survival curve of the squamous cell carcinoma patients with hnRNP B1 overexpresseion showed a better prognosis compared with that of the patients without hnRNP B1 expression (P=0.014), whereas in adenocarcinoma patients, there was no such a difference between them (P=0.889). These findings indicate that hnRNP B1 could be a useful marker for the early detection of bronchogenic squamous cell carcinoma and that it may be a prognostic factor in this cell type.

Biomarkers, Tumor↗
PubMed2003

An image method to evaluate bagasse fiber dimensions.

In the last 25 years the amount of textile nonwovens used for industrial and commercial applications increased more than 10 times. Bagasse fiber, a by-product from sugar cane industry, provides a natural resource for nonwoven industries. Even though underrated as a potential fiber, bagasse comes more and more into attention because of the increasing concern for disposal of agricultural residuals and the need for enhancing the sugar cane industry's profitability. However, there is a lack of an instrumental method to evaluate bagasse fiber length and fineness. This paper presents a study on measuring the bagasse fineness using image analysis method. Cross-sections images of bagasse fibers were visualized using Scanning Electronic Microscopy (SEM). The computing software Scion Image was used to measure bagasse fiber length and cross-sectional area. Relationship between fiber fineness and cross-sectional area was analyzed using the statistical method of regression.

Cellulose↗
PubMed2003

Identification of minimal peptide sequences in the (8-20) domain of human islet amyloid polypeptide involved in fibrillogenesis.

We have examined a series of overlapping peptide fragments from the 8-20 region of human islet amyloid polypeptide (IAPP) with the objective of defining the smallest fibril-forming domain. Peptide fragments corresponding to LANFLV (residues 12-17) and FLVHSS (residues 15-20) were strong enhancers of beta-sheet transition and fibril formation. Negative stain electron microscopy illustrated the ability of these peptide fragments to form fibrils independently when incubated alone in solution. Circular dichroism analysis revealed that when full-length human IAPP was incubated in the presence of these two fragments, fibrillogenesis was accelerated. While the two fragments, LANFLV and FLVHSS, were able to enhance the recruitment of additional IAPP molecules during fibril formation, the "seeding" activity of these peptides had no effect on altering IAPP-induced cytotoxcity as determined by cell culture studies. Therefore, this study has identified two internal IAPP peptide fragments within the 8-20 domain that may have a role in enhancing the folding and aggregation of human IAPP. These fragments are the smallest sequences identified, within the 8-20 region of hIAPP, that can independently form fibrils, and that can interact with IAPP to assemble into fibrils with characteristics similar as those formed by human IAPP alone.

Amyloid↗
PubMed2003

An optimization algorithm for intensity modulated radiotherapy--the simulated dynamics with dose-volume constraints.

We have developed a new method for optimization in intensity modulated radiation therapy (IMRT) that makes use of simulated dynamics in a classical system of interacting particles. An analogy is drawn between intensity profile optimization in IMRT and relaxation to the equilibrium configuration in a dynamic system. The intensities of beamlets are equivalent to the positions of the virtual particles. The potential energy of the system is defined by the objective function, which determines the equations of motion for the virtual particles. In this paper, we present the implementation of dose constraints and dose-volume constraints. Our strategy is to optimize the dose to the planned target volume (PTV) while keeping all constraints to the organs at risk (OARs) satisfied rigorously. A simple quadratic objective function is used that only includes terms for PTV voxels. By this approach, no additional parameters other than that for prescribing desired dose and constraints, such as importance factors, are needed. The hard constraints that require non-negative beamlet intensities and that the dose at any voxel in an OAR cannot exceed a maximum tolerance, are implemented as semi-transmittable potential barriers of infinite height. Dose-volume constraints are handled by placing hard constraints on partial volumes. Handling of the clinically applied constraints was tested using phantoms and clinical cases. Our results show that the dose-volume histogram (DVH) type of plan prescription can be fulfilled with satisfactory PTV coverage. In addition to the convenience of implementation, our method can achieve a high computational efficiency with the understanding of the dynamic behavior of the system.

Algorithms↗
PubMed2003

Beam orientation optimization for IMRT by a hybrid method of the genetic algorithm and the simulated dynamics.

We have developed a new method for beam orientation optimization in intensity-modulated radiation therapy (IMRT). The problem of beam orientation optimization in IMRT is solved by a decoupled two-step iterative process: (1) optimization of the intensity profiles for given beam configurations; (2) selection of optimal beam configurations based on the ranking by an objective function score for the results of the intensity profile optimization. The simulated dynamics algorithm is used for the intensity profile optimization. This algorithm enforces both the hard constraints and dose-volume constraints. A genetic algorithm is used to select beam orientation configurations. The method has been tested for both a simulated and clinical case, and the results show that beam orientation optimization significantly improved IMRT plans within a time period that is clinically acceptable. The results also show the dependence of the optimal orientation configurations on the prescribed constraints. In addition, beam orientation optimization by the method described here can provide multiple plans with similar dose distributions. This degeneracy characteristic can be exploited to our advantage in introducing additional planning objectives, e.g., the smoothness of intensity profiles, for the selection of the optimal plan among the degenerate configurations for treatment delivery.

Algorithms↗
PubMed2003

Differential effects of rosiglitazone on skeletal muscle and liver insulin resistance in A-ZIP/F-1 fatless mice.

To determine the role of adipocytes and the tissue-specific nature in the insulin sensitizing action of rosiglitazone, we examined the effects of 3 weeks of rosiglitazone treatment on insulin signaling and action during hyperinsulinemic-euglycemic clamps in awake A-ZIP/F-1 (fatless), fat-transplanted fatless, and wild-type littermate mice. We found that 53 and 66% decreases in insulin-stimulated glucose uptake and insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase activity in skeletal muscle of fatless mice were normalized after rosiglitazone treatment. These effects of rosiglitazone treatment were associated with 50% decreases in triglyceride and fatty acyl-CoA contents in the skeletal muscle of rosiglitazone-treated fatless mice. In contrast, rosiglitazone treatment exacerbated hepatic insulin resistance in the fatless mice and did not affect already reduced IRS-2-associated PI 3-kinase activity in liver. The worsening of insulin action in liver was associated with 30% increases in triglyceride and fatty acyl-CoA contents in the liver of rosiglitazone-treated fatless mice. In conclusion, these data support the hypothesis that rosiglitazone treatment enhanced insulin action in skeletal muscle mostly by its ability to repartition fat away from skeletal muscle.

Adipocytes↗
PubMed2003

[Screening of candidate genes in a family with autosomal dominant retinitis pigmentosa].

OBJECTIVE: To determine the causative mutation in a 5 generation pedigree with autosomal dominant retinitis pigmentosa (ADRP). METHODS: Genomic DNA from four patients and 4 normal persons in the same pedigree suffering ADRP were extracted, and subsequently eight exons of three ADRP candidate genes were screened for mutations by a combined polymerase chain reaction-single strand conformation polymorphism and DNA sequencing techniques. RESULTS: A new point mutation in rhodopsin gene at codon 52 of exon 1 (TTC to TAC) that resulted in a substitution of Tyr to Phe was detected in the four affected family members, but not in the four control individuals from the same pedigree. CONCLUSION: A causative mutation of rhodopsin gene was identified in a large Chinese pedigree with ADRP. The present study confirmed the molecular genetic heterogeneity of ADRP.

Adult↗
PubMed2003

[A clinical and pathological study on primary oral mucosal malignant melanoma].

OBJECTIVE: The aim of this study was to investigate the association between clinical and pathological characteristics of primary oral mucosal malignant melanoma and the prognosis of this disease. METHODS: Clinical and pathological characters of 73 cases primary oral mucosal malignant melanoma were investigated. The association between risk factors, such as black macule, lymph node metastases, invasive depth, clinic stages, pathologic types, and prognosis was analyzed using Kaplan-Meier survival analysis and Log rank test. RESULTS: The age of the patients ranged from 24 to 80 years (Median age, 50). Among the patients, 43 were males and 30 were females. The most common locations of the tumor were palate and gingiva. The clinic stages of these patients were as the following: Stage I (46/73), Stage II (24/73), Stage III (3/73). The most common pathological type was nodular (44/73), followed by lentiginose malignant melanoma (15/73) and superficial spreading (1/73). According to the configuration of tumor cells, the most common type was the mixed cell type (37/73), followed by the epitheloid cell type (27/73) and the spindle cell type (9/73). Among the 73 patients, 43 were followed up, the 3-year and 5-year survival rates were 19.86% and 11.91% respectively. Black macule, lymph node metastases, invasive depth, clinic stages, pathologic types and therapeutic methods were significantly associated with the prognosis (P < 0.05). CONCLUSION: The prognosis of the primary oral mucosal malignant melanoma is associated with black macule, lymph node metastases, invasive depth, clinic stages, pathologic types, and therapeutic methods.

Adult↗
PubMed2003

[Effects of Epstein-Barr virus latent membrane protein 1(EBV-LMP1) on related factors of metastasis of nasopharyngeal carcinoma cell line CNE1].

BACKGROUND & OBJECTIVE: It has been proved that Epstein- Barr virus (EBV) latent membrane protein 1 (EBV-LMP1) can induce the expression of matrix metalloproteinase-9 (MMP-9). This study was designed to investigate the effect of EBV-LMP1 on related factors of metastasis of nasopharyngeal carcinoma cell line CNE1. METHODS: Expression of MMP-9 was studied in human NPC cell lines cultured in vitro: CNE1 (well differentiated cell line of NPC) and CNE1-GL (CNE1 cell line transfected with an eukaryotic LMP1-expression plasmid) by SP immunohistochemistry and Western blot analysis. Cell-matrix adhesion assay was used to study the adhesive ability of CNE1-GL cells. The effects of LMP1 on the invasion and migration of CNE1 cells were investigated by transwell methods. RESULTS: MMP-9 was expressed in both cell lines but the intensity of the staining was different. The positive rates of expression of MMP-9 in CNE1 and CNE1-GL cells were 30.2% and 98.2%, respectively (P< 0.05). The increased expression of MMP-9 was also shown in CNE1-GL cells by Western blot analysis. Cell-matrix adhesion assay showed that the adhesive ability of CNE1-GL with the matrix (mean A value: 1.2508+/-0.0711) was higher than that of CNE1 cell (mean A value: 0.9519+/-0.068) (P< 0.001). Invasion assay and migration assay showed that the invasion and migration of CNE1-GL cell were higher than those of CNE1 cells (P< 0.01). CONCLUSION: The transfection of LMP1 can increase the expression of MMP-9 in CNE1 cells. Abilities of adhesion, migration, and invasion of CNE1 cell were induced by LMP1. It is suggested that MMP-9 may have a role in the LMP1-induced acceleration of invasion and metastasis of NPC cells.

Cell Adhesion↗
PubMed2003

Effects of low doses of hydrochloride tetracycline on bone metabolism and uterus in ovariectomized rats.

AIM: To study the effects of low doses of hydrochloride tetracycline (Tc) on bone metabolism and uterus in the ovariectomized (Ova) rats. METHODS: Forty 3-month-old rats were randomly divided into 5 groups: sham group, Ova group, Tc1 group (1.2 mg/kg/d), Tc2 group (4.8 mg/kg/d), and estrone group (1.48 mg/kg/d), oral fed for 3 months. The proximal tibia metaphyses were processed undecalcified for quantitative bone histomorphometry and the soft tissues were processed in paraffin for pathological observation. RESULTS: Placebo-treated (lactose) Ova rats were characterized by trabecular area (TA) decreasing and their architecture worsening compared with sham controls, and bone resorption was over formation with high bone turnover. The uteri were atrophy. (2) In estrone-treated group, TA and trabecular numbers were significantly increased and the trabecular separation decreased vs Ova group. Estrone slowed down Ova-inducing bone high turnover. But the size, weight, and the endometrium of the uteri in this group were increased vs Ova group. (3) TA was increased in both Tc1 and Tc2 groups compared with Ova rats. Tc maintained bone formation indices almost at Ova level, and only decreased mineral apposition rate (MAR) in Tc1 group, and declined bone resorption perimeter. The uteri and the cell of liver and kidney almost maintained at Ova level; Tc2 decreased labeling perimeter and increased MAR in comparison with Tc1 group. The uteri were atrophy, whose size maintained at Ova level; yellow labeling was not found in bone with these doses of Tc, while yellow labeling could be seen with the doses of 30 mg/kg/d of Tc for bone marker. CONCLUSION: The two doses of Tc have similar effects on preventing bone loss in Ova rats while the bone formation and uterus are not affected. However, Tc2 does not have more effects on increasing bone mass, Tc2 causes less mild damages to the liver and kidneys.

Animals↗
PubMed2003

[Antitumor effects of soluble TRAIL in human hepatocellular carcinoma].

OBJECTIVE: To investigate therapeutic potential of soluble TRAIL (sTRAIL) in hepatocellular carcinoma (HCC). METHODS: Expression of TRAILR was determined by in situ hybridization in 60 samples of resected hepatocellular carcinoma, 20 samples of normal liver tissue near the margin of benign tumor and 2 HCC cell lines of HepG2 and SMMC-7721. The clinical data of the patients were analyzed as well as cellular effects of sTRAIL in promoting apoptosis on HCC cell lines HepG2 and SMMC-7721 (p53 gene mutated) after exposure to different concentrations of recombinant protein. RESULTS: High death receptor (DR) expression and low DcR expression in HCC tissue differed from low DR expression and high DcR expression in the normal hepatic tissue with statistical significance. DR5, DR4, and DcR2 but not DcR1 were expressed in both cell lines. The expression of DR was closely correlated with HCC differentiation, with the weak expression in poor differentiation. The positive rate of DR expression in 32 cases of grade III-IV was significantly lower than that in 28 cases of grade I-II (P < 0.05). Cell apoptosis rates were 10%, 70% and 50% of HCC cells, Jurkat cells and human cholangiocarcinoma cell line QBC939 24 h after recombinant of TRAIL alone. CONCLUSION: TRAILR expression is prevalent in HCC, with different receptor types existing. HCC is resistant to TRAIL-mediated apoptosis. The treatment of TRAIL alone only has a limited effect on inducing apoptosis on HCC cell lines of HepG2 and SMMC-7721.

Adolescent↗
PubMed2003

[Interleukin-12 enhanced tumor necrosis factor related apoptosis-inducing ligand TRAIL-induced apoptosis in human hepatocellular carcinoma by inhibiting expression of survivin].

OBJECTIVE: To investigate therapeutic potential of TRAIL in hepatocellular carcinoma (HCC) and the mechanism of sTRAIL resistance and to reverse the resistance to sTRAIL-inducing apoptosis. METHODS: The expression profiles of TRAILR were determined 60 HCC samples, in 20 normal liver tissues and 2 HCC cell lines HepG2 and SMMC-7721 by in situ hybridization. Cellular effects of sTRAIL in promoting apoptosis on HCC cell lines HepG2 and SMMC-7721 were analyzed after exposure to recombinant protein and after transfection with a cDNA expression construct. In vivo effects of sTRAIL on tumor growth were investigated using a nude mice HCC model of hepG2. Furthermore, the expression of survivin in HCC was detected, and treatment with antisence oligonucleotide was accepted. Finally, therapeutic effect on HCC by combining sTRAIL and interleukin-12 (IL-12) was detected. RESULTS: Both DR4 and DR5 were present in all HCC tissues as well as normal hepatic tissues. In contrast, 54 HCC tissues did not express DcR1 and 25 did not express DcR2. But both DcR were detectable in all of the normal liver tissues. The expression patterns of DR and DcR in HCC samples were quite different from those in normal tissue. DR5, DR4, and DcR2 expressed in both cell lines, while no DcR1 expression was detected. Recombinant sTRAIL alone was found to have a slight activity as it killed a maximum of 15% of HCC cells within 24 h while killing over 70% of Jurkat cells. In vivo administration of the TRAIL gene couldn't inhibit tumor growth in a nude mice HCC model. Mostly, HCC tissue and both HCC cell lines expressed survivin, whereas normal liver tissue did not express survivin. Treatment with antisence oligonucleotide enhanced sTRAIL-inducing apoptosis. IL-12 significantly augmented sTRAIL-inducing apoptosis and inhibited survivin expression. CONCLUSIONS: HCC cells are insensitive towards TRAIL-mediated apoptosis. Survivin may play a role in resistance to TRAIL-induced apoptosis in HCC, and antisence oligonucleotide could partly reverse the resistance to TRAIL-inducing apoptosis. IL-12 may sensitize HCC cells to TRAIL-induced apoptosis by preventing survivin. Combining gene therapy strategy such as combining gene therapy of TRAIL with IL-12 may be a promising maneuver to HCC.

Animals↗
PubMed2003

[Analysis of glucocorticoid receptor gene polymorphisms by denaturing high-performance liquid chromatography].

OBJECTIVE: To detect polymorphisms of glucocorticoid receptor gene (NR3C1) in Chinese population with the technique of denaturing high-performance liquid chromatography (DHPLC). METHODS: Genomic DNA was isolated from peripheral blood of 2 healthy volunteer doctors and umbilical cord blood of 62 normal neonates. All the NR3C1-coding exons along with their flanking intron portions were amplified by polymerase chain reaction (PCR). For polymorphism screening, PCR products were analyzed by DHPLC. DNA fragments with aberrant elution profiles revealed by DHPLC were re-amplified and sequenced directly. RESULTS: Eight polymorphisms were identified by DHPLC and sequencing analysis. Among them, 5 (1374A > G, IVSG-68_IVSG-63delAAAAAA, 2193T > G, IVSH-9C > G, 2382C > T) were novel and 3 (1896C > T, 2166C > T, 2430T > C) were reported previously. Two groups of polymorphisms ([1374A > G + IVSG-68_IVSG-63delAAAAAA + IVSH-9C > G + 2382C > T] and [1896C > T + 2166C > T + 2430T > C]) showed to have the complete linkage disequilibrium and were identified as 2 different haplotypes, which was first reported. The frequencies of the 2 novel haplotypes were 3.1% and 14.1%, respectively. Another polymorphism (2193T > G) was relatively rare. CONCLUSION: DHPLC is a rapid and reliable method for polymorphism screening. Eight polymorphisms in the NR3C1 gene are detected in Chinese population with the technique of DHPLC, of which two haplotypes have been identified for the first time.

Asian People↗