Search PubMed⌕ Search

Biomedical subjects

M Wood

Publications and source records attributed to M Wood.

At least 163 records · Page 9Linked to original sources

Imaging with ion beams and laser postionization.

We investigate the use of a liquid metal ion gun (LMIG) combined with multiphoton resonance ionization of sputtered atoms and/or molecules to acquire mass-selected images with submicrometer spatial resolution. Images from several model systems are presented including those of an In grid, and of patterned surfaces of benzo[a]pyrene and tryptophan thin films. Since postionization for these systems yields ionization efficiencies that are considerably higher than those achieved with secondary ion mass spectrometry (SIMS), spatial resolution of 2600 A for molecular species could be achieved while static conditions were maintained. Cooling of the sample to < 210 K was shown to be essential for molecular systems since the number of thermally evaporating molecules overwhelms the number of sputtered molecules at room temperature. Other details necessary to incorporate laser postionization into a time-of-flight SIMS instrument using a pulsed LMIG source are also discussed.

Benzo(a)pyrene↗

Cross-linking CD28 leads to activation of 70-kDa S6 kinase.

Proliferation of T lymphocytes in response to antigen/MHC complexes is dependent upon the presence of a co-stimulatory signal; in its absence, T cells are rendered unresponsive to specific antigen CD28 is a T cell surface glycoprotein that acts as a co-stimulatory molecule when combined with signals initiated by the T cell receptor CD3 complex. While the biochemical signaling events following CD28 stimulation are still poorly defined, monoclonal antibodies (mAb) directed against CD28 have been shown to transduce a variety of early signals that are different in the presence of cross-linking antibody or the presence of phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC). Stimulation of human T cells with cross-linked anti-CD28 mAb alone resulted in the activation of 70-kDa (p70) S6 kinase, a rapamycin-sensitive serine/threonine kinase that is believed to be important for cell cycle progression. Activation of p70 S6 kinase through CD28 was inhibited by rapamycin. Activation of p70 S6 kinase also increased in response to cross-linked CD3, but followed a more rapid time course than activation via CD2. Cyclosporin A and FK506 had no effect on p70 S6 kinase activity initiated via either pathway. The combination of cross-linked CD28 and cross-linked CD3 had no more than an additive effect on the induction of p70 S6 kinase activity. Thus, recruitment of p70 S6 kinase activity appears to represent a common signal transduction event shared by both the CD28 and CD3 pathways of T cell activation.

CD28 Antigens↗

Activation of 70-kDa S6 kinase, induced by the cytokines interleukin-3 and erythropoietin and inhibited by rapamycin, is not an absolute requirement for cell proliferation.

The cytokines interleukin (IL)-3 and erythropoietin (EPO) are critical regulators of the proliferation and differentiation of cells of the hematopoietic system, but their intracellular mechanisms of action are not fully understood. Binding of IL-3 to the IL-3 receptor (IL-3R) and binding of EPO to the EPOR both induce changes in intracellular tyrosine and serine/threonine phosphorylation; the phosphorylation of a number of polypeptides appears to be a shared response upon cytokine stimulation. We have previously shown that binding of IL-2 to the IL-2R activates the 70-kDa (p70) S6 kinase, a serine/threonine kinase whose activity is regulated by serine/threonine phosphorylation; the immunosuppressant rapamycin inhibits IL-2-dependent proliferation and IL-2-triggered activation of p70 S6 kinase. We, therefore, sought to examine whether induction of p70 S6 kinase activity is a conserved response upon cytokine triggering, and whether this activity is essential for cell proliferation. Proliferation of the IL-3-dependent pro-B cell line Ba/F3 transfected with the EPOR (Ba/F3-EPOR) can be supported by either IL-3 or EPO. In this cell line, both IL-3 and EPO induced p70 S6 kinase activity; rapamycin inhibited both the IL-3 and EPO-induced activation of the 70-kDa S6 kinase as well as cellular proliferation. Thus, p70 S6 kinase activation appears to be a common intermediate triggered by the stimulation of IL-3, EPO, and IL-2 receptors. The Friend spleen focus-forming virus gp55 renders the EPOR constitutively active, and confers growth factor independence on cells expressing EPOR. Ba/F3-EPOR cotransfected with gp55 (Ba/F3-EpoRgp55) and the erythroleukemia cell line MEL, which also expresses both the EPOR and gp55, were analyzed. Rapamycin inhibited the activation of p70 S6 kinase in both cell lines. However, rapamycin inhibited proliferation of Ba/F3-EpoRgp55 but not of MEL cells despite inhibition of p70 S6 kinase activity in both cells. Thus, p70 S6 kinase activation is not an absolute requirement for cell proliferation. These results are discussed in relation to the role of the activation of the 70-kDa S6 kinase activation pathway in the regulation of cell cycle progression.

Animals↗

Victim to abuser: mental health and behavioral sequels of child sexual abuse in a community survey of young adult males.

Respondents in a stratified random sample of 750 males aged 18 to 27 in Calgary, Canada were asked to recall unwanted sexual contacts occurring before their 17th birthday: 117 (15.6%) had experienced one or more unwanted sexual contacts. Those recalling multiple events of abuse (52 individuals, 6.9% of all respondents) were distinguished from other respondents at a statistically significant level on the following indicators: emotional abuse in childhood, higher rates of current or recent depression, anxiety, suicidal feelings and behavior, and current sexual interest in or actual behavior involving minors. The combination of emotional abuse in the respondent's childhood with multiple events of sexual abuse was a relatively good predictor of both poor mental health, and later sexual interest in or sexual contact with children. Eight apparently active pedophiles were identified, using a computer response system that assured anonymity. This study underscores the need for preventive measures, and the prompt identification and treatment of victims before they enter the victim-to-abuser cycle.

Adaptation, Psychological↗

Analysis of remote reflection spectroscopy to monitor plant health.

Remote non-contact reflection spectroscopy is examined as a method for detecting stress in Controlled Ecological Life Support System CELSS type crops. Lettuce (Lactuca [correction of Latuca] Sativa L. cv. Waldmans Green) and wheat (Triticum Aestivum L. cv. Yecora Rojo) were grown hydroponically. Copper and zinc treatments provided toxic conditions. Nitrogen, phosphorous, and potassium treatments were used for deficiency conditions. Water stress was also induced in test plants. Reflectance spectra were obtained in the visible and near infrared (400nm to 2600nm) wavebands. Numerous effects of stress conditions can be observed in the collected spectra and this technique appears to have promise as a remote monitor of plant health, but significant research remains to be conducted to realize the promise.

Algorithms↗

Metabolism of cytochrome P4503A substrates in vivo administered by the same route: lack of correlation between alfentanil clearance and erythromycin breath test.

Because there is considerable interindividual variation in both microsomal CYP3A4 activity and CYP3A4 substrate disposition, an established probe of in vivo CYP3A4 activity would represent an important advance in clinical practice. In a previous study, no correlation was found between the 14C-erythromycin breath test and urinary dapsone recovery ratio. However these drugs were administered by different routes, with the orally administered dapsone being exposed to presystemic metabolism by the gut and renal metabolism before the measurement of the urinary ratio. To overcome the variable of route of administration, the aim of this study was to determine whether the elimination of two intravenously administered CYP3A4 substrates (alfentanil and erythromycin) correlate. We compared the metabolism of alfentanil to its CYP3A4-dependent metabolite, noralfentanil, with the erythromycin breath test in 14 young healthy white men. No significant correlation was found between alfentanil metabolism and the erythromycin breath test: alfentanil clearance versus erythromycin breath test, r = 0.45, p = 0.1; partial metabolic clearance to noralfentanil versus erythromycin breath test, r = 0.35, p = 0.23. Because these two CYP3A4 substrates were administered by the same (intravenous) route, we conclude that differences in the route of administration do not explain the lack of correlation between the erythromycin breath test and other probes of CYP3A4 metabolism.

Adult↗

Recent insights in programmed electrical stimulation for the management of sustained ventricular arrhythmias.

After more than 20 years of clinical use, programmed electrical stimulation for induction of cardiac arrhythmias remains an important clinical and research tool. The procedure continues to undergo refinement but is not without controversy regarding its accuracy in predicting drug efficacy as determined by serial testing for suppression of ventricular tachyarrhythmias. Recent work has streamlined technical aspects of the procedure itself and promises to improve the selection of patients likely to benefit from such studies. Despite these advances, however, recent publications from the Electrophysiologic Study Versus Electrocardiographic Monitoring trial raise fundamental questions about the ability of any current strategy to predict the efficacy of antiarrhythmic drugs for the prevention of ventricular arrhythmias.

Anti-Arrhythmia Agents↗