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Biomedical subjects

F Ren

Publications and source records attributed to F Ren.

At least 19 recordsLinked to original sources

Genotype may correlate with liver carcinogenesis and tumor characteristics in cirrhotic patients infected with hepatitis B virus subtype adw.

To identify the influence of hepatitis B virus (HBV) genotype on development of hepatocellular carcinoma (HCC) and clinical outcome in chronic HBV infection, 26 consecutive cirrhotic patients infected with HBV subtype adw were investigated prospectively. HBV serology was undertaken using subtype-specific antibodies against hepatitis B surface antigens. The HBV genotype was determined by sequencing directly the polymerase chain reaction products of the HBV S gene. When HCC occurred, patients underwent transcatheter arterial embolization therapy. If tumor necrosis was incomplete, additional embolization therapy was carried out after a 3- to 4-month interval. At a median follow-up of 14.1 years (range 2.2 to 31.7), HCC occurred in 9 (35%) of 26 patients. Nineteen patients were infected with genotype B and 7 with genotype C. Four of the 19 genotype B patients (21%) and 5 of the 7 genotype C patients (71%) developed HCC (P = 0.058). Patient age (<45 years or 45 < or = ) at diagnosis of cirrhosis was the only significant independent factor influencing liver carcinogenesis by multiple logistic regression analysis and Cox's regression analysis (P = 0.0069 and 0.029, respectively). When analysis was limited to the age of 45 years or more at the last visit, genotype was the only contributory factor to HCC development by univariate analysis (P = 0.038). Whereas genotype B patients responded well to embolization therapy and had no recurrence of HCC for a prolonged period of time, genotype C patients showed poor responses and died of hepatic failure due to rapid HCC progression despite embolization therapy. The cumulative incidence of survival was significantly higher in the genotype B group (P = 0.0049). The HBV genotype correlated with the development of HCC, response to embolization therapy, and recurrence of HCC. Determination of HBV genotype may be useful in predicting outcomes in HBV subtype adw-related cirrhosis.

Adult↗

A new algorithm for analysis of within-host HIV-1 evolution.

A new algorithm for inferring the evolution of within-host viral sequences is presented. A sequential-linking approach is developed so that a longitudinal phylogenetic tree can be reconstructed from sequential molecular data that are obtained at different time points from the same host. The algorithm employs a codon-based model, which uses a Markov process to describe substitutions between codons, to calculate nonsynonymous and synonymous substitution rates and to distinguish positive selection and neutral evolution. The algorithm is applied to a data set of the V3 region of the HIV-1 envelope genes sequenced at different years after the infection of a single patient. The results suggest that this algorithm may provide a more realistic description of viral evolution than traditional evolutionary models, because it accounts for both neutral and adaptive evolution, and reconstructs a longitudinal phylogenetic tree that describes the dynamic process of viral evolution.

Algorithms↗

Inference and prediction of courses of the diseases caused by pathologic viruses by estimating molecular evolution of within-host virus.

A new approach for inferring the evolutionary process of within-host virus is presented in this study. This approach includes a sequential-linking algorithm developed by us that can deal with the sequential viral samples that are obtained at different time points from the same host, and reconstruct a longitudinal phylogenetic tree in which the evolutionary relations between viral variants can be shown. A codon-based model, which uses a Markov process to describe substitutions between codons, is also employed in this approach to calculate synonymous and non-synonymous substitution rates and to distinguish positive selection and neutral evolution. The approach is applied to a data set of the V3 region of the HIV-1 envelope genes sequenced in different years after infection of a single patient. The results suggest that this approach may provide a more realistic description of viral evolution than the traditional evolution models because it accounts for both neutral and adaptive evolution. Most important of all, since this approach make it possible to follow up the evolutionary process of within-host virus by analyzing the sequential viral samples, it could be used in inference and prediction of the course of the diseases caused by pathologic viruses and evaluation of the treatment.

Algorithms↗

Design of experiment and data analysis by JMP (SAS institute) in analytical method validation.

Validation of an analytical method through a series of experiments demonstrates that the method is suitable for its intended purpose. Due to multi-parameters to be examined and a large number of experiments involved in validation, it is important to design the experiments scientifically so that appropriate validation parameters can be examined simultaneously to provide a sound, overall knowledge of the capabilities of the analytical method. A statistical method through design of experiment (DOE) was applied to the validation of a HPLC analytical method for the quantitation of a small molecule in drug product in terms of intermediate precision and robustness study. The data were analyzed in JMP (SAS institute) software using analyses of variance method. Confidence intervals for outcomes and control limits for individual parameters were determined. It was demonstrated that the experimental design and statistical analysis used in this study provided an efficient and systematic approach to evaluating intermediate precision and robustness for a HPLC analytical method for small molecule quantitation.

Chromatography, High Pressure Liquid↗

Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells.

Androgens via their cognate receptor may be involved in the development and progression of prostate cancer. The aim of this study was to determine whether tea polyphenols have inhibitory effects on androgen action in an androgen-responsive, prostate cancer cell line, LNCaP. The tea polyphenol, EGCG, inhibited LNCaP cell growth and the expression of androgen regulated PSA and hK2 genes. Moreover, EGCG had a significant inhibitory effect on the androgenic inducibility of the PSA promoter. Immunoblotting detected a decrease in androgen receptor protein with treatments of the tea polyphenols EGCG, GCG and theaflavins. Northern blot analysis showed decreased levels of androgen receptor mRNA by EGCG. Transient transfections demonstrated that EGCG and theaflavins could repress the transcriptional activities of the androgen receptor promoter region. An Sp1 binding site in the androgen receptor gene promoter is an important regulatory component for its expression. This study suggests Sp1 is the target for the tea polyphenols because treatments of EGCG decreased the expression, DNA binding activity and transactivation activity of Sp1 protein. In conclusion, we have described a new property of tea polyphenols that inhibits androgen action by repressing the transcription of the androgen receptor gene.

5' Untranslated Regions↗

Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel.

It has been suggested that the administration of an anti-progesterone might improve bleeding patterns in women with irregular bleeding while using low-dose progestin-only contraception. We report the findings of a double-blind, randomized, placebo-controlled trial of mifepristone 50 mg taken once every 4 weeks in 100 Chinese women (50 subjects and 50 controls) complaining of frequent and irregular bleeding while using a levonorgestrel-releasing subdermal contraceptive implant. In all women, regardless of treatment, the frequency of bleeding decreased significantly over 360 days of observation. Women recorded significantly shorter episodes of bleeding (P: < 0.0002) during mifepristone treatment than during the 90 days before treatment started. In contrast, the duration of bleeding episodes fell more gradually in placebo-treated controls. Women using mifepristone were more likely to find treatment acceptable than women receiving a placebo tablet (P: < 0.01). Despite concern that anti-progestogenic effects may jeopardize contraception, there were no pregnancies. This approach may offer a useful strategy to improve continuation rates by alleviating unwanted side-effects until bleeding patterns improve spontaneously with time.

Adolescent↗

Purification, characterization, and molecular cloning of the gene of a seed-specific antimicrobial protein from pokeweed.

A small cysteine-rich protein with antimicrobial activity was isolated from pokeweed (Phytolacca americana) seeds and purified to homogeneity. The protein inhibits the growth of several filamentous fungi and gram-positive bacteria. The protein was highly basic, with a pI higher than 10. The entire amino acid sequence of the protein was determined to be homologous to antimicrobial protein (AMP) from Mirabilis jalapa. The cDNA encoding the P. americana AMP (Pa-AMP-1) and chromosomal DNA containing the gene were cloned and sequenced. The deduced amino acid sequence shows the presence of a signal peptide at the amino terminus, suggesting that the protein is synthesized as a preprotein and secreted outside the cells. The chromosomal gene shows the presence of an intron located within the region encoding the signal peptide. Southern hybridization showed that there was small gene family encoding Pa-AMP. Immunoblotting showed that Pa-AMP-1 was only present in seeds, and was absent in roots, leaves, and stems. The Pa-AMP-1 protein was secreted into the environment of the seeds during germination, and may create an inhibitory zone against soil-borne microorganisms. The disulfide bridges of Pa-AMP-1 were identified. The three-dimensional modeling of Pa-AMP-1 indicates that the protein has a small cystine-knot folding, a positive patch, and a hydrophobic patch.

Amino Acid Sequence↗

Topology selection in unrooted molecular phylogenetic tree by minimum model-based complexity method.

In reconstruction of phylogenetic trees from molecular data, it has been pointed out that multifurcate phylogenetic trees are difficult to be correctly reconstructed by the conventional methods like maximum likelihood method(ML). In order to resolve this problem, we have been engaged in developing a new phylogenetic tree reconstruction method, based on the minimum complexity principle widely used in the inductive inference. Our method, which we call "minimum model-based complexity (MBC) method", has been proved so far to be efficient in estimating multifurcate branching when the tree is described in the form of rooted one. In this study, we make further investigations about the efficiency of MBC method in estimating the multifurcation in unrooted phylogenetic trees. To do so, we conduct computer simulation in which the estimations by MBC method are compared with those by ML, AIC and statistical test approach. The results show that MBC method also provides good estimations even in the case of multifurcate unrooted trees and suggest that it could be generally used for reconstruction of phylogenetic tree having arbitrary multifurcations.

Biological Evolution↗

[Studies on hepatitis B virus infection in blood donors with positive anti-HBc and negative HBsAg].

OBJECTIVE: To study if it is necessary to screen for core antibody against hepatitis B (anti-HBc) to prevent post-transfusion hepatitis B and what is its criteria for screening. METHODS: Relationship between the titer of anti-HBc and HBV DNA in blood from qualified donors by routine testing was conducted. HBV DNA was detected in 297 units of blood with anti-HBc at various titers by immuno-nested polymerase chain reaction (RT-PCR). RESULTS: HBV DNA was detected in one of four units of blood with positive anti-HBc at a dilution of equal to or greater than 1:128, and no HBV DNA was detected in other 75 units of blood with a dilution of anti-HBc less than 1:128. There was significant relationship between HBV DNA and the titer of anti-HBc. No HBV DNA was detected in 218 units of blood with both positive anti-HBc and anti-HBs and in 50 units with negative anti-HBc. Detection rate of HBV DNA in blood with positive anti-HBc was only 0.34% (1/297). CONCLUSION: Blood containing higher titer of single anti-HBc may be infectious. It is suggested that sensitivity of the reagents for detecting HBsAg currently used (1 ng/ml) be improved with the limited budget.

Adult↗

The application of model-based complexity inference method to molecular evolution analysis.

In this study, a new method based on the concept of complexity in inductive inference is proposed for reconstructing molecular phylogenetic tree. This method describes the complexity of molecular phylogenetic tree by three terms, which are related to tree topology, the branch lengths and fitness between the model and data measured by likelihood function. The computer simulation is used to investigate the efficiency of this method. The results suggest that this method is superior to the traditional methods because it avoids excess-complexity in the tree model estimation available from DNA sequence.

Base Sequence↗

[Relationship between change of erythrocyte membrane lipid composition and pregnancy induced hypertension].

OBJECTIVE: To study the cause of decreased erythrocyte deformability and its relation to pregnancy induced hypertension (PIH). METHODS: The cholesterol and phospholipid content of erythrocyte membrane in 24 non-pregnant healthy women, 22 normotensive pregnant women and 36 cases with PIH were determined using automatic biochemical analysor, Gas chromatography and modified colorimetric method. RESULTS: The cholesterol content and the cholesterol/phospholipid (C/P) ratio of the erythrocyte membrane were obviously higher in the group with moderate or severe PIH than that in the nonmotensive pregnancies (P < 0.01). There was no significant difference between mild PIH group and the normotensive pregnant group (P > 0.05). CONCLUSION: The increase of cholesterol content and C/P ratio in the erythrocyte membrane might be involved in the pathophysiology of PIH. The alteration of cholesterol content in the erythrocyte membrane probaby reflected the disturbance of serum lipid metabolism.

Adult↗

Inference of molecular phylogenetic tree based on minimum model-based complexity method.

In this study, starting with a newly introduced concept of data complexity ("empirical data complexity"), we specify the concept of complexity more concretely in relation to mathematical modeling and introduce "model-based complexity (MBC)". Inductive inference based on the minimum model-based complexity method is then applied to the reconstruction of molecular evolutionary tree from DNA sequences. We find that minimum MBC method has good asymptotic property when DNA sequence lengths approach to infinite and compensates the bias of maximum likelihood method due to the difference of tree topology complexity. The efficiency of minimum MBC method for reconstruction of molecular tree is studied by computer simulation, and results suggest that this method is superior to the traditional maximum likelihood method or its modification by Akaike's AIC.

Animals↗

Construction of molecular evolutionary phylogenetic trees from DNA sequences based on minimum complexity principle.

Ever since the discovery of a molecular clock, many methods have been developed to reconstruct the molecular evolutionary phylogenetic trees. In this paper, we deal with the problem from the viewpoint of an inductive inference and apply Rissanen's minimum description length principle to extract the minimum complexity phylogenetic tree. Our method describes the complexity of the molecular phylogenetic tree by three terms which are related to the tree topology, the sum of the branch lengths and the difference between the model and the data measured by logarithmic likelihood. Five mitochondrial DNA sequences, from the human, the common chimpanzee, the pygmy chimpanzee, the gorilla and the orangutan, are used for investigating the validity of this method. It is suggested that this method might be superior to the traditional method in that it still shows good accuracy even near the root of phylogenetic trees.

Algorithms↗

[24-hour esophageal pH monitoring for suspected esophageal originated chest pain].

Thirty patients with suspected esophageal originated chest pain were studied by 24 h esophageal pH monitoring. All of them complained of chest pain, heart burn, acid reflux or dysphagia. The result showed abnormal pH in 26 patients (86.7%). Sixteen of them had pH abnormalities in both day and night, whereas 8 had only abnormal day pH, and 2 pH out of the normal limits at night. Chest pain episode was correlated with the abnormalities in 18 cases (60%). Four patients with coronary heart disease showed simultaneous gastro-esophageal reflux originated chest pain; the positive correlation was obtained. Their diagnosis of cardiac chest pain was doubtful. We suggested that 24h pH monitoring was a significant method to determine the cause of chest pain.

Adolescent↗

Identification of a 12.5-kD protein from caudate-putamen nucleus as a dopaminergic neuronotrophic factor.

The effect of the extract from caudate-putamen nucleus of newborn rats (CPe) on the dopaminergic (DA) neurons has been studied. An MTT colorimetric microassay measuring optical densities for the growth of DA neuron cultures reveals a significant increase in growth for cultures with CPe as compared to those without CPe (p < 0.05). Rhodamine retrograde-prelabelled DA neurons were cultured on a Phastgel containing all the electrophoretically separated protein bands from CPe, and able to fish out from it their own trophic factor, a 12.5-kD protein band. The survived neurons at the 12.5-kD protein band were immunostained positive with anti-dopamine antibody. Co-culturing the 12.5 kD-containing gel strip with explants from substantia nigra at a close distance for a week revealed anti-dopamine immunopositive neurites outgrowing from the explants only towards the 12.5-kD gel strip. These results indicate that a 12.5-kD protein from the CPe is capable of maintaining the survival of DA neurons of the substantia nigra and promoting their neurite outgrowth.

Animals↗

[Growth inhibitory action of RGNTF-McAb on human retinoblastoma cell line Y-79].

The monoclonal antibody against the retinal ganglion neuronotrophic factor (RGNTF-McAb) was used in immunostaining of the Western blotting membrane separated from extract of human retinoblastoma cell line Y-79 to find that the latter contained a 30KD protein which was immunologically similar to the RGNTF secreted from the tectum of rat. The effect of different concentrations of RGNTF-McAb on the growth of Rb cells in cultures of different seeding concentrations was studied, revealing that the growth inhibitory action of RGNTF-McAb increased with increasing concentrations, up to 67% inhibition. Morphologically the growth and division of Rb cells were significantly inhibited as compared to the controls. The RGNTF-anti-idiotypic antibody was used for the localization of the RGNTF receptor, which the immunoreactive positive staining indicated to be on the surface of Rb cell membrane. The RGNTF-McAb could thus neutralize the RGNTF and inhibit growth of the Rb cells. These findings support the application of RGNTF-McAb to the treatment of retinoblastoma.

Antibodies, Anti-Idiotypic↗