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Biomedical subjects

M Han

Publications and source records attributed to M Han.

At least 55 records · Page 3Linked to original sources

[Effect of yiqi jianpi drugs on apoptosis and relevant gene expression in cultured vascular smooth muscle cell].

OBJECTIVE: To explore the effect of Yiqi Jianpi (YQJP, supplementing Qi and invigorating Spleen) recipe on vascular smooth muscle cells (VSMC) apoptosis and it's mechanisms. METHODS: VSMC apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nicked labeling (TUNEL) analysis, transmission electron microscope (TEM), flow cytometry and DNA agarose electrophoresis. The expression activity of bcl-2, c-myc and p53 genes were determined using Northern blotting. RESULTS: The typical characteristics of apoptotic VSMC was observed following treatment by the YQJP drug serum. The DNA extracted from VSMC revealed a ladder pattern in electrophoresis. Flow cytometric analysis revealed G0/G1 stage cell blocking phenomena, the hypodiploid apoptotic cell increased, displayed typical peak of apoptosis, the rate of cell apoptosis and YQJP serum concentration were in a dose-dependent manner. The result of hybridization showed that 30% of YQJP serum could inhibit apoptotic gene bcl-2 expression, upregulated the level of apoptogenous gene c-myc and p53 mRNA. CONCLUSION: VSMC apoptosis could be induced by YQJP recipe and its mechanism might be through affecting the apoptosis related gene expression activity.

Animals↗

Current Clinical Applications of the In-capromab Pendetide Scan (ProstaScint(R) Scan, Cyt-356).

Prostate-specific antigen (PSA) has been extremely helpful in the detection of new or recurrent prostate cancer. However, localization of the recurrent tumor has been challenging with currently available radiographic modalities. The (111)In-capromab pendetide scan was developed to diagnose accurately and, more importantly, localize and stage a new or recurrent prostate cancer. Studies suggest that the (111)In-capromab pendetide scan can provide more accurate staging of clinically localized prostate cancer prior to staging lymphadenectomy or definitive therapy. It can also provide valuable information when local adjuvant radiation therapy is considered in men with biochemical cancer recurrence following radical prostatectomy.

Journal Article↗

A neural network predicts progression for men with gleason score 3+4 versus 4+3 tumors after radical prostatectomy.

OBJECTIVES: To determine the significance of Gleason scores 3+4 (GS3+4) versus 4+3 (GS4+3) with respect to biochemical recurrence in a retrospective review of a series of men with clinically localized prostate cancer who underwent radical retropubic prostatectomy (RRP) and to develop and test an artificial neural network (ANN) to predict the biochemical recurrence after surgery for this group of men using the pathologic and clinical data. METHODS: From 1982 to 1998, 600 men had pathologic Gleason score 7 disease without lymph node or seminal vesicle involvement. We analyzed the freedom from biochemical (prostate-specific antigen) progression after RRP on 564 of these men on the basis of their GS3+4 versus GS4+3 (Gleason 7) status. The Cox proportional hazards model was used to determine the importance of Gleason 7 status as an independent predictor of progression. In addition, an ANN was developed using randomly selected training and validation sets for predicting biochemical recurrence at 3 or 5 years. Different input variable subsets, with or without Gleason 7 status, were compared for the ability of the ANN to maximize the prediction of progression. Standard logistic regression was used concurrently on the same random patient population sets to calculate progression risk. RESULTS: A significant recurrence-free survival advantage was found in men who underwent RRP for GS3+4 compared with those with GS4+3 disease (P <0.0001). The ANN, logistic regression, and proportion hazard models demonstrated the importance of Gleason 7 status in predicting patient outcome. The ANN was better than logistic regression in predicting patient outcome, in terms of prostate-specific antigen progression, at 3 and 5 years. CONCLUSIONS: A simple modification of the Gleason scoring system for men with Gleason 7 disease revealed a difference in the patient outcome after RRP. ANN models can be developed and used to better predict patient outcome when pathologic and clinical features are known.

Disease Progression↗

sem-4 promotes vulval cell-fate determination in Caenorhabditis elegans through regulation of lin-39 Hox.

Vulval cell-fate determination in Caenorhabditis elegans requires the action of numerous gene products, including components of the Ras/Raf/MAPK signaling cascade and the hox gene lin-39. sem-4 encodes a zinc finger protein with previously characterized roles in fate specification of sex myoblasts, coelomocytes, and multiple neuronal lineages in C. elegans (M. Basson and R. Horvitz, 1996, Genes Dev. 10, 1953-1965). By characterizing three new alleles of sem-4 that we identified in a screen for vulval-defective mutants, we determined that loss of sem-4 activity results in abnormal specification of the secondary vulval cell lineages. We analyzed sem-4 interactions with other genes involved in vulval differentiation and determined that sem-4 does not function directly in the Ras-mediated signal transduction pathway but acts in close association with and upstream of lin-39 to promote vulval cell fate. We demonstrate that sem-4 regulates lin-39 expression and propose that sem-4 is a regulator of lin-39 in the vulval cell-fate determination pathway that may act to link lin-39 to incoming signals.

Alleles↗

The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf.

Caenorhabditis elegans sur-8 encodes a positive regulator of Ras signaling. We investigated the mechanism by which the human Sur-8 homolog can positively regulate Ras-MAP kinase signaling in mammalian cells. Sur-8 expression enhances Ras- or EGF-induced Raf and ERK activation but has no effect on ERK activation induced by active Raf or MEK. Furthermore, Sur-8 expression does not increase AKT or JNK activation. Sur-8 interacts with Ras and Raf and is able to form a ternary complex with the two proteins. Thus, Sur-8 may function as a scaffold that enhances Ras-MAP kinase signal transduction by facilitating the interaction between Ras and Raf.

Adaptor Proteins, Signal Transducing↗

The use of molecular diagnostics in bladder cancer.

Bladder cancer is a common disease that causes significant morbidity and mortality in the United States. Early detection and routine surveillance are recommended in the management of this chronic and recurrent disease. Cystoscopic examination has been used for detection and follow-up; however, it is costly and is associated with patient discomfort. With advances in molecular biology and biochemistry, many diagnostic assays have been developed to supplement cystoscopy. The mechanisms and variable results of these assays are described. In addition, the economic and social implications of bladder cancer detection and surveillance are discussed.

Journal Article↗

Building a protein interaction map: research in the post-genome era.

With the extensive amount of information generated by genome-wide sequencing, the entire set of gene products in an organism can now be predicted. The challenge of understanding the function of each gene in the genome has led to the development of many large-scale and high-throughput experimental techniques. Recently, two papers, Walhout et al.(1) and Uetz et al.,(2) have described studies that add a new functional dimension to research conducted on a genome-wide scale. These two groups have utilized the yeast two-hybrid system to identify interactions among the entire complement of proteins encoded by the Caenorhabditis elegans and the Saccharomyces cerevisiae genomes, respectively. Using a set of 29 genes that have been previously characterized, Walhout et al. demonstrated the feasibility and efficiency of this technique by building an interaction matrix among a large number of proteins. On an even larger scale, Uetz et al. conducted two-hybrid analyses using proteins that represent over 87% of the total gene products in yeast and identified interactions for about 15% of the total yeast proteins. BioEssays 22:503-506, 2000.

Animals↗

The synthetic multivulval genes of C. elegans: functional redundancy, Ras-antagonism, and cell fate determination.

Development of the C. elegans vulva requires coordination between a strikingly complex set of molecular regulators and pathways. In particular, the correct specification of vulval cell-fates requires both the activation of RTK/Ras/Map kinase members as well as negative regulation by a set of genes known as the SynMuvs. SynMuvs comprise two functionally redundant sets of genes that appear to antagonize Ras pathway signaling. In this way, SynMuv genes act to limit the number of cells adopting vulval fates. Recently, a number of SynMuv genes have been shown to encode worm homologs of the Rb transcriptional-regulatory complex. These and other results are discussed and we present several models for understanding the role of SynMuv genes in vulval development.

Animals↗

The role of free prostate-specific antigen in prostate cancer detection.

Prostate-specific antigen (PSA) is the most important serum tumor marker for prostate cancer detection. Free PSA is one of the many molecular forms of PSA that have been identified. Percent free PSA improves the specificity (elimination of unnecessary biopsies) for prostate cancer detection in men with nonsuspicious digital prostate examination and total serum PSA ranges between 4 and 10 ng/mL. Further study is necessary to determine the optimal clinical utility of percent free PSA in men with a total serum PSA level of less than 4 ng/mL. In addition, the level of free PSA may be affected by many factors, including age, prostate volume, prostate manipulation, sample handling, and type of assay used.

Age Factors↗

A new locus for dominant drusen and macular degeneration maps to chromosome 6q14.

PURPOSE: To report the localization of a gene causing drusen and macular degeneration in a previously undescribed North American family. METHODS: Genetic mapping studies were performed using linkage analysis in a single family with drusen and atrophic macular degeneration. RESULTS: The clinical manifestations in this family ranged from fine macular drusen in asymptomatic middle-aged individuals to atrophic macular lesions in two children and two elderly patients. We mapped the gene to chromosome 6q14 between markers D6S2258 and D6S1644. CONCLUSIONS: In a family with autosomal dominant drusen and atrophic macular degeneration, the gene maps to a 3.2-cM region on chromosome 6q14. This locus appears to be distinct from, but adjacent to, the loci for cone-rod dystrophy 7 (CORD7) and North Carolina macular dystrophy (MCDR1). Future identification of the gene responsible for the disease in this family will provide a better understanding of macular degeneration.

Adolescent↗

Getting signals crossed in C. elegans.

The induction of an appropriate cellular response to a stimulus often depends on the intricate interplay between multiple signaling pathways. Recent work utilizing Caenorhabditis elegans has enabled the identification of points of convergence between signaling pathways and permitted the elucidation of how multiple signals work in concert to ensure a proper response.

Animals↗

An activated carbon substrate surface for laser desorption mass spectrometry

A method to obtain laser desorption/ionization mass spectra of organic compounds by depositing sample solutions onto a carbon substrate surface is demonstrated. The substrate consists of a thin layer of activated carbon particles immobilized on an aluminum support. In common with the porous carbon suspension samples used in previous "surface-assisted laser desorption/ionization" (SALDI) work, the mass spectra contain only a few "matrix" background ion peaks, minimizing interference with analyte ion peaks. The presence of glycerol ensured that the ion signals were stable over hundreds of laser shots. In addition, the carbon substrate surface has several advantages over the suspension samples. The use of a very thin layer of carbon significantly improves the sensitivity. Detection limits range from attomoles for crystal violet to femtomoles for bradykinin. Very little sample preparation is required as the analyte solution is simply pipetted onto the substrate surface and glycerol added. When using an alternate sample deposition method, a mass resolution for bradykinin of 1800 is achieved in linear time-of-flight mode. This is close to the resolution limit set by the detector system and above instrument specification for matrix-assisted laser desorption/ionization mass spectra.

Journal Article↗

Comparative study of induction of iNOS mRNA expression in vascular cells of different species.

To determine the difference in induction of inducible nitric oxide synthase (iNOS) mRNA expression in cultured vascular cells of different species, the expression of iNOS genes and their regulatory mechanisms in rat, human, bovine, and rabbit vascular endothelial cells and smooth muscle cells (SMC) were studied by Northern blotting, chloramphenicol acetyltransferase (CAT) assay, and electrophoretic mobility shift assay (EMSA). Qualitative estimation of iNOS mRNA by Northern-blot analysis demonstrated that the combination of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and lipopolysaccharides (LPS) drastically induces iNOS expression in rat and human SMC, and a more moderate effect was observed for endothelial cells; the effect of IL-1 beta alone was much weaker than that of the three factors. IL-1 beta alone or a mixture of IL-1 beta, TNF-alpha, and LPS both showed negligible effect on iNOS expression in bovine and rabbit vascular endothelial cells and SMC. Results of CAT assay corresponded well with Northern analysis indicating 7-fold increase in CAT activity by the mixture of IL-1 beta, TNF-alpha, and LPS in SMC and more moderate, 2-fold increase, in endothelial cells. IL-1 beta alone produced an intermediate effect (less than 2-fold) on vascular SMC of rats and humans. The results of EMSA showed that two shifted bands appeared when the nuclear protein from rat and human vascular endothelial cells bound to the region from -1037 to -787 of the rat iNOS gene, while vascular SMC nuclear protein only produced a single shifted band under the same conditions. These results suggest that cell- and species-specific mechanisms exist in the induction of iNOS expression.

Animals↗