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Biomedical subjects

N Wang

Publications and source records attributed to N Wang.

At least 505 records · Page 28Linked to original sources

Proteolytic and metastatic activities of clones derived from a methylcholanthrene-induced murine fibrosarcoma.

Eighteen clones of a methylcholanthrene-induced murine fibrosarcoma (3AM) which were heterogeneous with respect to metastatic potentials and in vivo growth rates were examined for five different protease activities: acid protease (cathepsin D), BANA hydrolase (cathepsin B), neutral protease, collagenase, and plasminogen activator. Homogenates of the solid tumors produced by the clones were heterogeneous with respect to the activities of the proteases; these activities were in all cases (except plasminogen activator) higher than those obtained for normal muscle tissue. There was, however, no correlation between any of these protease activities and the metastatic potential or in vivo growth rates. The cathepsin B activity has also been evaluated on the cultured cells of the various clones. Results similar to that of the in vivo study were obtained. Analysis of the enzyme activity of the cell culture and of organ culture media, however, revealed no cathepsin B activity. It is concluded that the measurement of any one biochemical parameter such as proteolysis may not be sufficient to establish a correlation with the overall process of metastasis; a more precise dissection of the individual steps culminating in metastasis may provide a more fruitful approach to this problem.

Aminopeptidases↗

Expression of a specific protein in spontaneously metastatic fibrosarcoma cell lines and its enhanced synthesis by growth on laminin or fibronectin.

A panel of tumor cell lines and clones was generated by selecting for different metastatic capacity in 3AM fibrosarcoma cells. These cell lines were exposed to substrata of various purified extracellular matrix (ECM) proteins and labeled in culture with [35S]methionine. Following analysis by two-dimensional polyacrylamide gel electrophoresis the profiles of total cellular proteins produced by the cell lines displaying different phenotypes were examined. The presence of a specific protein, p54, was related to the cellular metastatic potential, and the synthesis of p54 was influenced by growth on extracellular matrix components. The amount of p54 was minimal and non-inducible in tumor cell lines exhibiting two different phenotypes: (1) experimentally metastatic (EM) and (2) transformed, non-tumorigenic (NTT) cell types. In contrast, all of the five different cell lines capable of both spontaneous and experimental metastasis (SEM), produced p54 either constitutively or through induction by growth on ECM protein substrata of either laminin of fibronectin, but not collagen type IV. These data suggest that the p54 protein may be a unique biochemical marker associated with spontaneous metastatic cell types.

Animals↗

Two new 9,10-seco-cycloartanes from the seeds of Sphaerophysa salsula.

Two new 9,10-seco-cycloartanes, named sphaerophyside SC (1) and sphaerophyside SD (2), together with four known compounds (3-6), were obtained from the ethanol extract of the seeds of Sphaerophysa salsula. The structures of these compounds were elucidated on the basis of spectral and chemical evidences. Compounds 3-6 were isolated from the plant for the first time.

China↗

Emergency implantation of a left ventricular assist device in adolescents with biventricular failure.

Adolescents with congestive cardiomyopathy who present with intractable arrhythmia or progressive ventricular failure have a very poor prognosis and often die awaiting cardiac transplantation (CTx). We present our recent experience with a pneumatically powered left ventricular assist device (LVAD) implanted emergently to salvage adolescents with severe biventricular failure. Four patients, aged 15-17 years, body surface areas of 1.5-1.7 m2, with dilated cardiomyopathy (LV diastolic dimension, 7.1-8.3 cm); two presented with cardiovascular collapse, one with refractory ventricular tachycardia, and one with cardiac arrest. Hemodynamic and biochemical data before and 1 week after LVAD placement are expressed as mean and range values. None of the patients required right ventricular assist, and all patients achieved functional recovery while on LVAD support (8-71 days). Currently, all four patients are alive (11-22 months) after successful CTx. We conclude that emergency implantation of an LVAD in adolescents with biventricular heart failure can be life saving. As has been shown in the adult population, such a ventricular assist system restores normal circulatory hemodynamics, reverses multi-organ dysfunction, and provides a "safe" bridge to transplantation.

Adolescent↗

Probing transmembrane mechanical coupling and cytomechanics using magnetic twisting cytometry.

We recently developed a magnetic twisting cytometry technique that allows us to apply controlled mechanical stresses to specific cell surface receptors using ligand-coated ferromagnetic microbeads and to simultaneously measure the mechanical response in living cells. Using this technique, we have previously shown the following: (i) beta 1 integrin receptors mediate mechanical force transfer across the cell surface and to the cytoskeleton, whereas other transmembrane receptors (e.g., scavenger receptors) do not; (ii) cytoskeletal stiffness increases in direct proportion to the level of stress applied to integrins; and (iii) the slope of this linear stiffening response differs depending on the shape of the cell. We now show that different integrins (beta 1, alpha V beta 3, alpha V, alpha 5, alpha 2) and other transmembrane receptors (scavenger receptor, platelet endothelial cell adhesion molecule) differ in their ability to mediate force transfer across the cell surface. In addition, the linear stiffening behavior previously observed in endothelial cells was found to be shared by other cell types. Finally, we demonstrate that dynamic changes in cell shape that occur during both cell spreading and retraction are accompanied by coordinate changes in cytoskeletal stiffness. Taken together, these results suggest that the magnetic twisting cytometry technique may be a powerful and versatile tool for studies analyzing the molecular basis of transmembrane mechanical coupling to the cytoskeleton as well as dynamic relations between changes in cytoskeletal structure and alterations in cell form and function.

Animals↗

Gelatin nanoencapsulation of protein/peptide drugs using an emulsifier-free emulsion method.

The nanoencapsulation of a model protein drug, bovine serum albumin (BSA), using gelatin as the matrix material is reported. Nanoencapsulation was conducted using a modified water-in-oil (w/o) emulsion method, which is emulsifier-free and simple. The nanoencapsulation product, BSA-containing gelatin nanoparticles, is characterized in terms of nanoparticle morphology, size and size distribution, water content, and in vitro protein release. The BSA-containing gelatin nanoparticles obtained from this nanoencapsulation process are nearly spherical and have a log-normal size distribution. The average diameter of the BSA-containing gelatin nanoparticles is approximately 840 nm. They can absorb 51-72% of water. In vitro release experiments demonstrate that BSA has been successfully encapsulated in, and can be released from the gelatin nanoparticles. The release of BSA from the gelatin nanoparticulate matrix follows a diffusion-controlled release mechanism. It is found that temperature affects both the water content and the BSA release rate of the gelatin nanoparticles.

Chemistry, Pharmaceutical↗

Growth and behavioral development in plasminogen gene-targeted mice.

The plasminogen system, in addition to its major role in fibrinolyis, is believed to play a key role in development of the nervous system. The purpose of this study was to directly examine and quantify the importance of plasminogen in physical and behavioral development in plasminogen deficient mice (Plg-/-), plasminogen heterozygous mice (Plg+/-), and wild-type mice (Plg+/+, WT) at 2-21 days of age. Remarkably, little difference in growth and behavioral development was observed between Plg-/- and WT mice. Body weight gain and the milestones of physical development-ear detachment, eye opening and teeth eruption were similar from 2-21 days of age. Differences were found in physical development only after 4 wks of age, body weight gain was less and vaginal patency was delayed in the Plg-/- mice compared to WT mice. Behaviors, assessed during the 2-21 days of age period, developed in the Plg-/- mice in a pattern similar to WT mice. Specifically, no differences were found between Plg-/- and WT mice in the development of reflexes, neuromotor ability, motor coordination, locomotor activity, reaction to gravitational positioning, integration of motor and vestibular systems, olfactory development, and incidence of audiogenic seizure susceptibility. However, Plg-/- mice demonstrated a faster surface righting response and a faster latency for audiogenic seizure susceptibility, as well as an increase in the number of grooming bouts at age 17-21 days. These differences indicate that a plasminogen deficiency alters reactivity and the response to stress. The weight of the pituitary was smaller and pituitary and plasma corticotrophin releasing hormone were elevated in the Plg-/- mice compared to the WT mice. The results of this study suggest a role for the plasminogen system in hormone processing and neuroendocrine regulation.

Animals↗

A new cell proliferating marker: cytosolic thymidine kinase as compared to proliferating cell nuclear antigen in patients with colorectal carcinoma.

BACKGROUND: Proliferation markers are necessary for reliable diagnosis. Here we have presented for the first time thymidine kinase 1 (TK1) as a proliferative tumor marker for colorectal carcinoma. PATIENTS AND METHODS: Expression of TK1 in 54 colorectal lesions and 20 colorectal adenoma lesions was detected by immunohistochemistry technique (ABC). Proliferating Cell Nuclear Antigen (PCNA) was run in parallel. RESULTS: TK1-Labelling Index (LI) (65%) was higher than PCNA-LI (52%) in the malignant lesions, although not significantly different (p = 0.1717) between them. TK1-LI as well as PCNA-LI showed significant differences between colorectal carcinoma and colorectal adenoma (TK1 p = 0.0005, PCNA p = 0.0005). Both TK1-LI and PCNA were significantly different in respect to tumor stages (TK1 p = 0.0002, PCNA p = 0.0284). However, only TK1-LI showed significant difference in respect to tumor grades (p = 0.014), but not PCNA-LI (p = 0.132). CONCLUSION: TK1-LI showed more potential as a proliferating marker in colorectal carcinoma than PCNA-LI, especially for evaluating high-risk tumor grade and advanced stage in colorectal carcinoma.

Adenocarcinoma, Papillary↗

Chromosome 8 numerical aberration and C-MYC copy number gain in bladder cancer are linked to stage and grade.

Chromosome 8 aberration and c-myc amplification have been suggested as playing important roles in the development of different human cancers. Using fluorescence in situ hybridization (FISH), chromosome 8 polysomy and c-myc amplification can be detected in cells from bladder cancer. We investigated the correlation of chromosome 8 polysomy, c-myc gene alteration and p53 deletion with histopathological parameters. Twenty-four tumors obtained from patients with bladder cancer were analyzed by interphase cytogenetics using FISH with chromosome 8 and 17 centromere probes together with an YAC clone covering the c-myc locus and three cosmid DNA probes covering the p53 locus. Chromosome 8 polysomy was found in 12 tumors. The average copy number of chromosome 8 centromere signals were significantly higher in high grade and stage, cancers. Also the c-myc copy gain and p53 deletion were significantly correlated with grade as well as stage (p<0.05, in both cases). Both polysomy 8 and c-myc copy gain were significantly correlated with p53 deletions (p<0.01) and DNA ploidy (p<0.001). On the contrary there was no significant correlation between c-myc protein over-expression and c-myc gene amplification. These results may indicate that alteration of chromosomal regions on 8q and 17p, including c-myc and p53 genes, may be linked to progression of bladder cancer.

Carcinoma, Transitional Cell↗