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Biomedical subjects

J Gentry

Publications and source records attributed to J Gentry.

16 recordsLinked to original sources

Differential effect of selected methylxanthine derivatives on radiosensitization of lung carcinoma cells.

AIM: Using caffeine as a reference derivative, this study was performed to investigate how other methylxanthine derivatives, theophylline, 3-isobutyl-methylxanthine and 1,3-dipropyl-7-methylxanthine, sensitize cells to radiation by modifying cell cycle checkpoints and inducing the apoptotic response. The effect of the methylxanthine derivatives was studied in response to gamma and ultraviolet radiation in a human large cell lung carcinoma cell line, null for p53, a normal lung epithelial cell line and the large cell lung carcinoma cell line stably transfected with p53. METHODS: Effects of theophylline, 3-isobutyl-methylxanthine and 1,3-dipropyl 7-methylxanthine on cell-radiosensitization in comparison to caffeine tested by clonogenic survival assay, MTT assay, ELISA based apoptotic assay, flow cytometry, caspase-3 activity, TUNEL assay, and western blot analysis. RESULTS: All the derivatives, except 3-isobutyl-methylxanthine, increased tumor cell sensitization to radiation by inducing apoptosis in the p53-null lung cancer cell line. The pattern of cell cycle progression revealed that these derivatives increased the number of cells in G1 phase by abrogating the G2/M checkpoint, directing the cells to apoptose through a p53-independent mechanism. In contrast, 3-isobutyl-methylxanthine was more potent than the other derivatives in radiosensitization of normal lung epithelial cells and the lung carcinoma cells stably transfected with wild-type p53. IBMX increased p53 protein level more than caffeine in lung carcinoma cells stably transfected with wild-type p53. CONCLUSION: Our results suggest that 3-isobutyl-methylxanthine might function through a p53-dependent mechanism.

Apoptosis↗

The plasminogen-activating system in hepatic stellate cells.

Urokinase plasminogen activator (uPA) generates plasmin, a process inhibited by plasminogen-activator inhibitor (PAI)-1 and localized to the cell surface by binding of uPA to a specific receptor. Plasmin degrades extracellular matrix (ECM) both directly and by activation of matrix metalloproteinases (MMPs). Because stellate cells play a central role in the pathogenesis of liver fibrosis both via production of ECM proteins and through secretion of MMPs, their contribution to plasmin generation was assessed. Stellate cells were prepared from rat liver and cultured on plastic. Northern analysis showed cellular expression of messenger RNA (mRNA) for PAI-1, uPA, and uPA receptor. Zymography/reverse zymography identified cell-surface-associated uPA activity and uPA and PAI-1 in culture media. Net uPA activity in culture media was maximal after 7 days in culture and then declined, whereas PAI-1 antigen levels remained consistently elevated between 7 and 21 days in culture. Stellate cell-mediated plasmin generation was also seen in in vitro cultures supplemented with plasminogen. Because hepatic stellate cells (HSCs) contain retinoids and release them on activation, the effect of retinoic acid on the plasminogen-activating system was also assessed. Treatment of cultured HSCs with retinoic acid (1 micromol/L) increased uPA secretion 2.6-fold but did not alter PAI-1. We conclude that stellate cells synthesize key components of the plasminogen-activating system and generate plasmin and therefore have the ability to regulate MMP activation. Upregulation of uPA synthesis by retinoic acid may have implications in matrix remodeling in sites of stellate cell activation in which high concentrations of retinoids may be achieved.

Adipocytes↗

Rat hepatic lipocytes synthesize and secrete transin (stromelysin) in early primary culture.

BACKGROUND & AIMS: Hepatic lipocyte proliferation and activation are pivotal in liver fibrosis. Disruption of normal lipocyte-matrix interactions may contribute to this process. The synthesis of transin, which degrades normal liver matrix, by culture-activated hepatic lipocytes was investigated. METHODS: Lipocytes were isolated by pronase/collagenase perfusion, density gradient centrifugation, and centrifugal elutriation. Transin messenger RNA in lipocytes was analyzed by Northern blotting. Transin activity was analyzed by zymography, Western blotting, immunocytochemistry, and quantitative [14C]beta-casein degradation assay. RESULTS: Transin messenger RNA was detected in early primary culture (3-5 days) but not in freshly isolated lipocytes or late primary culture. Zymography of lipocyte medium showed caseinolytic activity (relative molecular weight, 57 kilodaltons and 60 kilodaltons) inhibited by ethyl-enediaminetetraacetic acid but not thiol or serine protease inhibitors. Immunoblotting and immunocytochemistry confirmed the presence of transin in media and cells. Quantitative transin activity decreased progressively with increasing duration of primary lipocyte culture and myofibroblastic transformation. CONCLUSION: Rat hepatic lipocytes express the transin gene and secrete its product during the early phase of lipocyte activation in primary culture. Because this enzyme degrades a wide spectrum of normal basement membrane proteins and activates progelatinase B and interstitial collagenase, it may have an important role in liver injury and fibrosis.

Adipocytes↗

Assessing work retention issues.

Within 6 months, a 10-member Nursing Services task force created and administered a literature-based retention survey. Tool development and administration is described. The 33-item tool was completed by 85% of the staff. Responses led to the formation of work groups, charged with addressing dissatisfiers and communicating implementation strategies to the hospital at large.

Adult↗

Extraction of light filth from tea: collaborative study.

The present AOAC method for determining insect and rodent filth in tea is time-consuming because it produced filter papers which are heavy in plant residue and therefore required long paper-reading times. A new method for the analysis of light filth in tea was developed to remedy existing problems and to improve recoveries. The method consists of the following steps: sample preparation, wet sieving, dilution with 40% isopropanol, flotation with mineral oil-heptane, and trapping off in a Wildman trap flask. In an interlaboratory collaborative study, analysts reported combined insect fragment recoveries of 99.2% for the proposed method and 93.0% for the AOAC method; the same analysts recorded combined rodent hair recoveries of 92.2% for the proposed method and 47.6% for the official method. Average times for reading individual subsamples were 9 min for the proposed method and 27 min for AOAC method. the proposed method has been adopted official first action.

Animals↗

The awesome burden upon the child who must keep a family secret.

This paper describes a series of young patients hospitalized in a psychiatric facility because they presented symptoms indicative of a psychotic disorder when, in fact, the youngsters were dealing with the strain of keeping a family secret hidden. Case presentation oriented to how the burden prohibited proper psychological development and the manner of how these secrets came to light are offered. The commonality of patients exhibiting this phenomenon is discussed.

Adolescent↗