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Biomedical subjects

T Turner

Publications and source records attributed to T Turner.

At least 55 records · Page 3Linked to original sources
PubMed1997

Molecular inhibition of phospholipase cgamma signaling abrogates DU-145 prostate tumor cell invasion.

Up-regulated signaling from the epidermal growth factor receptor (EGFR) has been correlated with tumor invasion and metastasis in numerous human neoplasias. Recently, we have demonstrated that increased levels of EGFR promote the invasiveness of human prostate carcinoma DU-145 cells. However, the intracellular signaling pathway responsible for this enhanced tumor invasiveness has not been identified. We postulated that increased cell motility signaled via phospholipase Cgamma (PLCgamma) activation was critical for tumor invasiveness. Highly invasive DU-145 cells engineered to overexpress the EGFR were stably transfected with a dominant-negative fragment of PLCgamma from the Z-region (PLCz) or with irrelevant peptide minigenes. PLCz was expressed only in the appropriate transfectant lines, with a concomitant decrease in inositol phosphate generation. The transfectant cell lines all formed tumors when inoculated into the peritoneal cavity of athymic mice. Tumors from the cells expressing PLCz fragment were significantly less invasive than the transfectants containing the control minigenes, as assessed by the diaphragm invasion model and invasion into abdominal soft organs. The cells expressing PLCz grew and formed colonies in soft agar at rates comparable to the cells expressing the control minigenes. These data suggest that up-regulated signaling by EGFR promotes prostate tumor invasiveness secondary to increased cell motility. Furthermore, PLCgamma represents a potential therapeutic target to limit tumor progression promoted by up-regulated signaling from the EGFR and related receptors with intrinsic tyrosine kinase activity.

Animals↗
PubMed1996

EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells.

Carcinomas of the prostate and other lineages often present an autocrine stimulatory loop acting via the EGF receptor (EGFR). We have recently shown that EGFR-mediated signals enhance DU-145 prostate carcinoma cell transmigration of an extracellular matrix in vitro, and that this increased invasiveness was independent of proteolytic degradation of the matrix (Xie et al., 1995, Clin Exp Metastasis, 13, 407). To determine whether up-regulated EGFR signaling promotes tumor progression in vivo and to define the EGFR-induced cell property responsible, we inoculated athymic mice with genetically-engineered DU-145 cells. Parental DU-145 cells and those transduced to overexpress a full-length wild type (WT) EGFR formed tumors and metastasized to the lung when inoculated in the prostate and peritoneal cavity. The WT DU-145 tumors were more invasive. DU-145 cells expressing a mitogenically-active, but motility-deficient (c'973) EGFR formed small, non-invasive tumors without evidence of metastasis. All three sublines demonstrated identical, EGFR-dependent rates of cell growth in vitro, suggesting that the differential invasiveness was not due to altered growth rates. To determine whether cell motility may be, in part, responsible for tumor invasiveness, we treated WT DU-145 intraperitoneal tumors with a pharmacologic agent (U73122) which blocks EGFR-mediated cell motility but not mitogenesis. Under this treatment regimen, the WT DU-145 cells formed tumors of similar numbers and size to those formed without treatment; however, these tumors were much less invasive. These data suggest that EGFR-mediated cell motility is an important mechanism involved in tumor progression, and that this cell property may represent a novel target to limit the spread of tumors.

Animals↗
PubMed1996

Mediators of the long-term impact of child sexual abuse: perceived stigma, betrayal, powerlessness, and self-blame.

Using a community sample of 192 adult women who had been sexually abused during childhood, the present study tested the hypothesis that perceived stigma, betrayal, powerlessness, and self-blame mediate the long-term effects of child sexual abuse. A path analysis indicated that the level of psychological distress currently experienced by adult women who had been sexually abused in childhood was mediated by feelings of stigma and self-blame. This result provides partial support for Finkelhor and Browne's (1985) traumagenic dynamics model of child sexual abuse. The limitations of the study are discussed.

Adult↗
PubMed1996

The relation between methods of coping during adulthood with a history of childhood sexual abuse and current psychological adjustment.

With a community sample of 192 women who had been sexually abused during childhood, the investigators determined if methods of coping in adulthood with the aftermath of child sexual abuse were associated with current symptoms of psychological distress. Multiple regression analyses indicated that disengagement methods of coping with the sexual abuse accounted for unique variance in general psychological distress even after controlling for characteristics of the abuse and methods of coping with other stressors. Disengagement methods of coping were also used more often to deal with the stressful aspects of having been sexually abused than to deal with other stressful events. In contrast, engagement methods of coping were used more often to deal with the other stressors than with sexual abuse.

Adaptation, Psychological↗
PubMed1996

The expression of stem cell factor and its receptor, c-kit in human endometrium and placental tissues during pregnancy.

Stem cell factor (SCF) and its receptor Kit regulate the proliferation and survival of early hematopoietic cell types as well as germ cells and melanocytes. As SCF augments the effects of several hematopoietic growth factors that are produced in reproductive tissues during pregnancy and also plays an important role in cell migration, proliferation, and survival, we studied the expression and localization of this receptor/ligand in human endometrial and placental tissues. Kit was detected by Western blot analysis in early decidual and placental tissues (8-19 weeks gestation) and in term placenta. Immunohistochemistry localized Kit mainly in trophoblast and to a lesser extent in scattered cells in the placental villous core and decidual stroma. Ribonuclease protection assay showed that SCF messenger ribonucleic acid (mRNA) expression increased 3-fold in decidua from early pregnancy compared to proliferative and secretory endometrium (P < 0.05). Placental tissues expressed 4- to 8-fold higher levels of SCF mRNA compared to decidus (P < 0.05). Isolated placental villous core expressed 7-fold higher levels of SCF mRNA than did trophoblast (P < 0.05). Thus, SCF and its receptor Kit are expressed in human endometrium and placental tissues during pregnancy, and the pattern of receptor/ligand expression suggests that endometrial and placental villous core SCF may have a paracrine effect on trophoblast through the receptor Kit.

Base Sequence↗
PubMed1995

In vitro invasiveness of DU-145 human prostate carcinoma cells is modulated by EGF receptor-mediated signals.

Prostate carcinomas often present an autocrine stimulatory loop in which the transformed cells both express the EGF receptor (EGFR) and produce activating ligands (TGF alpha and EGF forms). Up-regulated EGFR signalling has been correlated with tumor progression in other human neoplasia; however, the cell behaviour which is promoted remains undefined. To determine whether an EGFR-induced response contributes to cell invasiveness, we transduced DU-145 human prostate carcinoma cells with either a full-length (WT) or a mitogenically-active but motility-deficient truncated (c'973) EGFR. The DU-145 Parental and two transgene sublines all produced EGFR and TGF alpha, but the transduced WT and c'973 EGFR underwent autocrine downregulation to a lesser degree, with more receptor remaining intact. DU-145 cells transduced with WT EGFR transmigrated a human amniotic basement membrane matrix (Amgel) to a greater extent than did Parental DU-145 cells (175 +/- 22%). Cells expressing the c'973 EGFR invaded through the Amgel only to about two thirds the extent of the Parental cells (62 +/- 23%). A monoclonal antibody which prevents ligand-induced activation of EGFR decreased the invasiveness of WT-expressing cells by half and Parental cells by a fifth, but had little effect on the invasiveness of c'973-expressing cells; with the result that in the presence of antibody, all three cell lines transmigrated the Amgel to the same extent. The different levels of invasiveness between the three sublines were independent of cell proliferation. These findings demonstrated that EGFR-mediated signals increase tumor cell invasiveness and suggested that domains in the carboxy-terminus are required to signal invasiveness. As an initial investigation into the mechanisms underlying the EGFR-mediated enhanced invasiveness, we determined whether these cells presented different collagenolytic activity, as the major constituents of Amgel are collagen types I and IV. All three sublines secreted easily detectable levels of gelatin-directed proteases and TIMP-1, with WT cells secreting equivalent or lower levels of proteases. The proteolytic balance in these cells did not correlate with invasiveness. These data suggest that the TGF alpha-EGFR autocrine loop promotes invasiveness and that this is accomplished by signalling cell properties other than differential secretion of collagenolytic activity.

Carcinoma↗
PubMed1995

Mechanical ventilation may not be essential for initial cardiopulmonary resuscitation.

BACKGROUND: In a rodent model of cardiac arrest and resuscitation in which the inspired gas mixture was enriched with oxygen, resuscitability and survival were unaffected by positive pressure ventilation. In the present study, in a larger animal model, tidal volumes generated during precordial compression and with spontaneous gasping were quantitated. METHODS: Domestic pigs with an average weight of 34 kg were anesthetized with pentobarbital. Ventricular fibrillation (VF) was induced electrically. Precordial compression was begun after 4 min of untreated VF. Each of 22 animals received one of two interventions in conjunction with precordial compression: positive pressure ventilation with oxygen or oxygen supplied at the port of a tracheal tube at ambient pressure. After 8 min of precordial compression, defibrillation was attempted. RESULTS: Only very moderate increases in arterial PCO2 were documented during cardiopulmonary resuscitation in the absence of mechanical ventilation but arterial oxygen tension was consistently in excess of 100 mm Hg. Cardiac resuscitability and 48-h survival were approximately the same in animals maintained on inspired oxygen whether or not they were mechanically ventilated (7/11 or 8/11). In the absence of mechanical ventilation, precordial compression and spontaneous gasping yielded minute volumes that exceeded 5 L. CONCLUSION: Positive pressure mechanical ventilation did not improve resuscitability or postresuscitation outcome in this porcine model of cardiac arrest.

Animals↗
PubMed1994

Strategies for using university health services for cholesterol screening.

Seven hundred seventy students, parents, and employees participated in free cholesterol screenings during key promotional events at Central Michigan University between 1989 and 1992. Participants were self-selected volunteers who wanted to know their cholesterol levels. More than one third of the participants (32.4% of the students, 38.0% of the parents, and 54.3% of the employees) were found to have borderline or high cholesterol readings that put them at risk of coronary artery disease (CAD) because of hypercholesterolemia. The screening may have attracted subjects with a family history of CAD or other risk factors, and these individuals need follow-up lipid profiles and cholesterol education. The authors provide a description of the innovative approaches of their program and offer suggestions for promotional cholesterol screening programs.

Adolescent↗
PubMed1994

Spontaneous gasping increases the ability to resuscitate during experimental cardiopulmonary resuscitation.

OBJECTIVE: To evaluate the effect of spontaneous gasping on cardiorespiratory functions and the ability to resuscitate during experimental cardiac arrest. DATA SOURCES: Studies in rat and pig models during cardiac arrest and cardiopulmonary resuscitation (CPR). STUDY SELECTION: We retrospectively examined the role of spontaneous gasping during the course of experimental studies on cardiopulmonary resuscitation. DATA EXTRACTION: The data were extracted to illustrate the mechanisms of spontaneous gasping and its effects on pulmonary gas exchange and blood circulation during CPR. DATA SYNTHESIS: Spontaneous gasping increased PaO2 and decreased PaCO2 values during precordial compression in the absence of mechanical ventilation. The frequency of gasping during precordial compression was greater in successfully resuscitated animals. A significant linear correlation was established between coronary artery perfusion pressure and both the frequency (r2 = .90, p < .01) and the duration (r2 = 0.69, p < .01) of gasping during untreated ventricular fibrillation and before resuscitation was attempted. Like coronary perfusion pressure, the frequency and duration of gasping predicted the success of cardiac resuscitation attempts. CONCLUSIONS: Spontaneous gasping is associated with both pulmonary and hemodynamic effects during cardiac arrest in experimental animals. Spontaneous gasping is biologically useful and is predictive of a more favorable outcome of resuscitative efforts.

Animals↗
PubMed1994

School health. A message for Mrs. Bottomley.

School nurses in the Wandsworth health district are shortly to embark on a radical re-structuring programme to introduce teamworking and boost health promotion in schools. Toni Turner reports on a revitalised school nursing service.

Health Promotion↗
PubMed1992

Docking of dogs.

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Animal Welfare↗