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Biomedical subjects

G Mills

Publications and source records attributed to G Mills.

At least 37 records · Page 2Linked to original sources
PubMed1998

Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC.

Glioblastomas are highly malignant tumors of the central nervous system that are resistant to radiation and chemotherapy [1]. We explored the role of the phosphatidylinositol (PI) 3-kinase signal transduction pathway in glioblastomas, as this pathway has been shown to inhibit apoptosis induced by cytokine withdrawal and the detachment of cells from the extracellular matrix [2]. Components of this pathway have been implicated in tumor development [3-6]. We show that glioblastoma cells, in contrast to primary human astrocytes, contain high endogenous protein kinase B (PKB/Akt) activity and high levels of PI 3,4,5-triphosphate (PI(3,4,5)P3) and PI(3,4)P2, the lipid products of PI 3-kinase. These glioblastoma cells express mutant forms of the putative 3' phospholipid phosphatase PTEN, also known as MMAC. Expression of wild-type PTEN derived from primary astrocytes, but not of mutant forms of PTEN, reduced the levels of 3' phosphoinositides and inhibited PKB/Akt activity. PTEN antagonized the activation of PKB/Akt by growth factors, by activated PI 3-kinase and by PI-dependent protein kinase-1 (PDK1), but did not antagonize the phospholipid-independent activation of PKB/Akt lacking the pleckstrin homology (PH) domain. These results suggest a role for PTEN in regulating the activity of the PI 3-kinase pathway in malignant human cells.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed1998

Effects of high hydrostatic pressure on Clostridium sporogenes spores.

Spores of Clostridium sporogenes were found to be resistant to ultra high pressure, with treatments of 600 MPa for 30 min at 20 degrees C causing no significant inactivation. Combination treatments including heat and pressure applied simultaneously (e.g. 400 MPa at 60 degrees C for 30 min) or sequentially (e.g. 80 degrees C for 10 min followed by 400 MPa for 30 min) proved more effective at inactivating spores. Pressure cycling (e.g. 60 MPa followed by 400 MPa at 60 degrees C) also reduced spore numbers. Overall, these pressure treatments resulted in less than a 3 log reduction, and it was concluded that the spores could not be inactivated by pressure alone. This could indicate that for the effective inactivation of bacterial spores, high pressure technology may have to be used in combination with other preservation methods.

Clostridium↗
PubMed1997

Complying with current Joint Commission Statement of Conditions (SOC) requirements.

This Technical Document has been developed to provide the reader with insight into the Joint Commission on Accreditation of Healthcare Organizations' (JCAHO) Statement of Conditions (SOC) process and recent changes for completing the SOC for Business Occupancies. The intent of this document is not to replace the instructions in Part 1 of the SOC or to give a complete review of the National Fire Protection Agency's (NFPA) Life Safety Code for health care or business occupancies, but rather to complement them.

Accreditation↗
PubMed1996

Synthesis and anti-herpes virus activity of 2'-deoxy-4'-thiopyrimidine nucleosides.

A series of 5-substituted 2'-deoxy-4'-thiopyrimidine nucleosides was synthesized and evaluated as potential antiviral agents. A number of analogues such as 2'-deoxy-5-propyl-4'-thiouridine (3ii), 2'-deoxy-5-isopropyl-4'-thiouridine (3iii), 5-cyclopropyl-2'-deoxy-4'-thiouridine (3iv), 2'-deoxy-4'-thio-5-vinyluridine (3viii), and 5-(2-chloroethyl)-2'-deoxy-4'-thiouridine (3xx) were found to be highly active against herpes simplex virus type-1 (HSV-1) and varicella zoster virus (VZV) in vitro with no significant cytotoxicity. The compound with the broadest spectrum of activity was 2'-deoxy-5-ethyl-4'-thiouridine (3i) which showed significant activity against HSV-1, HSV-2, and VZV.

Animals↗
PubMed1995

Comparison of extradural fentanyl, bupivacaine and two fentanyl-bupivacaine mixtures of pain relief after abdominal surgery.

Fentanyl 50 micrograms, bupivacaine 50 mg and two mixtures containing fentanyl 50 micrograms and bupivacaine 25 mg or 12.5 mg (0.25 and 0.125%), respectively, in a volume of 10 ml were administered via thoracic extradural catheters to 24 patients after major abdominal surgery. All patients received all four treatments, in a randomized order, so that each patient received one of the 24 possible combinations of the four treatments. Pain relief was assessed by a linear analogue pain scale and the Prince Henry Hospital pain score. The duration of pain relief, effects on ventilatory frequency, heart rate, arterial pressure and central venous pressure were also recorded. Mean reductions in the analogue pain scale for fentanyl, bupivacaine, and fentanyl in 0.25% and 0.125% bupivacaine were 80 (SEM 5) %, 87 (4) %, 86 (5) % and 77 (5) %, respectively (ns). Pain scores decreased by 62 (6) %, 83 (5) %, 77 (6) % and 72 (6) %, respectively (ns). Mean arterial pressure decreased to 90 (2) %, 70 (2) %, 81 (2) % and 82 (3) %, respectively, of pretreatment values. In this respect, bupivacaine alone was significantly different from the three other treatments (P < 0.001). Hypotension (reduction in arterial pressure greater than 25% of pretreatment mean arterial pressure) was also more frequent after bupivacaine alone (P < 0.01). Effects on ventilation, heart rate and central venous pressure did not differ between the four treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Pain↗
PubMed1995

Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo.

Following exposure to some types of antigen (superantigens), responsive T cells expand and then decline in numbers, a phenomenon that has been called 'peripheral deletion'. This process may play a role in limiting autoimmune reactions and in the maintenance of immune homeostasis. Here we describe experiments on peripheral deletion in mice carrying the lpr/lpr defect, which has been shown to be due to defective production of the CD95/Fas molecule. Young lpr/lpr mice with no apparent immunologic abnormalities display a defect in bacterial superantigen-induced peripheral deletion. Apoptotic death of the expanded T cell population associated with such peripheral deletion. Apoptotic death of the expanded T cell population associated with such peripheral deletion in normal animals is dramatically reduced in the mutant mice. Further, the levels of Fas on responding cells in normal mice increases and decreases together with increases and decreases in cell numbers, suggesting that cells with the highest levels of Fas are preferentially deleted. These observations are consistent with the known ability of CD95 to transduce a signal leading to apoptosis, and they implicate this signal transduction pathway in peripheral deletion. In contrast, bacterial superantigen-induced deletion of thymocytes appears to be fully functional in these mice, and thus Fas/APO-1 does not appear to be required for this process. Further, antibody ligation of the TCR on activated T cells from normal or young lpr/lpr mice can induce apoptosis and therefore under some circumstances this phenomenon is not dependent upon CD95/Fas. Thus, to avoid autoreactivity and ensure immune homeostasis, several different apoptotic mechanisms exist in peripheral T lymphocytes, only some of which involve Fas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Mouth pressure in response to magnetic stimulation of the phrenic nerves.

BACKGROUND: Diaphragm strength can be assessed by the measurement of gastric (TW PGA), oesophageal (TW POES), and transdiaphragmatic (TW PDI) pressure in response to phrenic nerve stimulation. However, this requires the passage of two balloon catheters. A less invasive method of assessing diaphragm contractility during stimulation of the phrenic nerves would be of clinical value. A study was undertaken to determine whether pressure measured at the mouth (TW PM) during magnetic stimulation of the phrenic nerves accurately reflects TW POES, and to investigate the relations between TW PM and TW PDI; and also to see whether glottic closure and twitch potentiation can be avoided during these measurements. METHODS: Eight normal subjects and eight patients with suspected respiratory muscle weakness without lung disease were studied. To prevent glottic closure magnetic stimulation of the phrenic nerves was performed at functional residual capacity during a gentle expiratory effort against an occluded airway incorporating a small leak. TW PDI, TW POES, and TW PM were recorded. Care was taken to avoid potentiation of the diaphragm. RESULTS: In normal subjects mean TW PM was 13.7 cm H2O (range 11.3-16.1) and TW POES was 13.3 cm H2O (range 10.4-15.9) with a mean (SD) difference of 0.4 (0.81) cm H2O. In patients mean TW PM was 9.1 cm H2O (range 0.5-18.2) and TW POES was 9.3 (range 0.7-18.7) with a mean (SD) difference of -0.2 (0.84) cm H2O. The relation between TW PM and TW PDI was less close but was well described by a linear function. In patients with diaphragm weakness (low sniff PDI) TW PM was < 10 cm H2O. CONCLUSIONS: TW PM reliably reflects TW POES and can be used to predict TW PDI in normal subjects and patients without lung disease. TW PM may therefore be a promising non-invasive, non-volitional technique for the assessment of diaphragm strength.

Adult↗
PubMed1995

The effect of lung volume on transdiaphragmatic pressure.

Diaphragm strength can be assessed by measurement of transdiaphragmatic pressure (Pdi) in response to stimulation of the phrenic nerves. The length-tension relationship of the diaphragm can be studied by measuring twitch Pdi over the range of lung volume. Previous studies of the relationship between lung volume and diaphragm strength have used the technique of electrical stimulation of the phrenic nerves. In these studies, the phenomenon of twitch potentiation has not been taken into account. It has previously been shown that prior contraction of the diaphragm can greatly enhance the twitch response, thus affecting the measurements. The aim of this study was to investigate the relationship between unpotentiated twitch Pdi and lung volume for volumes ranging from residual volume (RV) to total lung capacity (TLC) in normal subjects. Great care was taken to avoid muscle potentiation. For this purpose, we stimulated the phrenic nerves with a magnetic stimulator. In addition, we used positive pressure to inflate the lungs to high lung volumes. The impact of twitch potentiation on the length-tension relationship was investigated by subjects making maximum inspiratory efforts prior to phrenic nerve stimulation. The unpotentiated twitch Pdi decreased in a linear fashion with increasing lung volume over the full range of vital capacity by 0.54 kPa.L-1. Potentiation increased twitch Pdi by 40% at FRC and the effect was similar, in absolute terms, at all lung volumes. In relative terms, the effect of potentiation became greater as lung volume increased, and more than doubled twitch Pdi at TLC. With increasing lung volume, there is a linear fall in unpotentiated twitch Pdi with a slope that is less steep, over the same range of absolute lung volume, than previously reported. When assessing diaphragm strength by the twitch technique, it is essential to control for lung volume and equally important to control for twitch potentiation.

Adult↗
PubMed1994

Transforming growth factor-beta inhibits proliferation of human ovarian cancer cells obtained from ascites.

BACKGROUND: Previously, the authors found that immortalized ovarian cancer cell lines generally were resistant to the growth inhibitory effect of transforming growth factor-beta and frequently had lost the ability to produce or activate this growth factor. In this study, the authors examined whether early passage epithelial ovarian cancer cells obtained from ascites are growth-inhibited by or produce transforming growth factor-beta. METHODS: Ovarian cancer cells were purified from ascites by percoll gradient density centrifugation, and inflammatory cells were removed using anti-CD45 antibody. The effect of transforming growth factor-beta on the proliferation of ovarian cancer cells was assessed using the thymidine incorporation assay. Immunohistochemical staining for transforming growth factor-beta 1 and beta 2 also was performed in these cells. RESULTS: Transforming growth factor-beta (10 ng/ml) significantly inhibited [3H]thymidine incorporation in 19 of 20 (95%) primary ovarian cancers (P < 0.05). In cases in which significant inhibition was seen, the mean thymidine incorporation was 33 plus or minus 28% of control values. In addition, there was no difference in dose-dependent inhibition of proliferation between ovarian cancer cells and normal ovarian epithelial cells. Eleven of 18 ovarian cancers (61%) were found to express immunohistochemically detectable transforming growth factor-beta, but immunostaining was not observed in 39% of cases. CONCLUSIONS: Although most primary ovarian cancer cells remain sensitive to the growth-inhibitory effect of transforming growth factor-beta, loss of production may interrupt the transforming growth factor-beta autocrine inhibitory loop and play a role in the development of some ovarian cancers.

Ascites↗