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Papers by Megan Delehanty

Research paper thumbnail of The effect of overexpression of activated rasB, rasC and rasS on Dictyostelium discoideum

Dictyostelium discoideum contains at least 5 ras genes. It had been previously demonstrated that ... more Dictyostelium discoideum contains at least 5 ras genes. It had been previously demonstrated that the expression of an activated rasG gene in D. discoideum resulted in cells which were unable to aggregate and a subset of which had a large, flattened morphology (Khosla et al, 1996. Mol. and Cell. Biol. 16: 4156-62). To investigate the role of the rasB, rasC, and rasS genes, an activating mutation (a glycine to threonine substitution at position 12) was made in each of the genes. The mutated genes were then expressed under the control of the inducible discoidin promoter. Overexpression of the rasC-G\2T and rasS-G\2T genes produced no evident abnormalities in cell morphology, growth, or development. Thus, rasC and rasS are not functionally equivalent to rasG, although no clues as to their roles in the cell were revealed. Overexpression of the ra.yf?-G12T gene resulted in the appearance of morphologically aberrent amoebae: a large proportion of the cells were large and flat with an incre...

Research paper thumbnail of Evelyn Fox Keller, Making Sense of Life: Explaining Biological Development with Models, Metaphors, and Machines . Cambridge, Mass.: Harvard University Press, 2002

Metascience, 2003

How have various forms of explanation-the models, metaphors, and machines of the subtitle-contrib... more How have various forms of explanation-the models, metaphors, and machines of the subtitle-contributed to biologists' understanding of development over the course of the last century? This book is not a philosophical work on explanation, and the reader expecting it to be one will be disappointed. Instead, it is a largely historical and, to some extent, sociological, survey of what has counted as an explanation, for whom and, in a limited way, why. While Keller makes passing reference to some standard philosophical concerns about explanation, this is not her focus. This might be taken to be a serious flaw in the book, but it must be acknowledged that she explicitly states that her goal is not to resolve extant questions about the nature of explanation, but rather to raise new questions. Furthermore, she describes her work here as "empirical rather than philosophical (at least in the strict sense of the term), and hence as complementing rather than supplementing more traditional work in the philosophy of explanation" (p. 5). The question, then, is whether she really does raise new questions and whether these questions open up new directions for inquiry into the nature of explanation? The book is divided into three sections. In the first, Keller explores several explanations of development that were developed in the first part of the twentieth century using mathematical or material models. (Model organisms are mentioned only in passing at the beginning of Chapter 2 and in the introduction to the second section of the book.) She focuses primarily on the work of Stéphane Leduc, D'Arcy Thompson, and Alan Turing and examines how the models developed by these men failed to exert any substantial influence on experimental biology, noting the existence of an epistemic divide between theoretical and experimental biology with early versions of a mathematical biology at this time falling clearly within the realm of the theoretical. These models were largely non

Research paper thumbnail of Emergent properties and the context objection to reduction

Emergent properties and the context objection to reduction

Biology & Philosophy, 2005

... the question of whether or not multiple realizability really does create insuperable difficul... more ... the question of whether or not multiple realizability really does create insuperable difficulties for ... Importantly, MDC do not limit satisfactory mechanisms to linearly orga-nized sequences. ... shows why under-standing mechanisms can help in the debate about reduction in biology. ...

Research paper thumbnail of Extending the mechanism: Dealing with the context objection to reduction

Research paper thumbnail of Empiricism and the Epistemic Status of Imaging Technologies

Research paper thumbnail of Polarized T Helper 2 Cell (TH2) Intracellular Cytokine Synthesis in Burn Patients with Hypertrophic Scarring

Polarized T Helper 2 Cell (TH2) Intracellular Cytokine Synthesis in Burn Patients with Hypertrophic Scarring

Journal of Burn Care & Rehabilitation, 2001

Research paper thumbnail of The changing landscape of the philosophy of medicine

The changing landscape of the philosophy of medicine

Philosophy Compass

Research paper thumbnail of Session 3: Natural selection as a causal theory

Session 3: Natural selection as a causal theory

... Session 3: Natural Selection as a Causal Theory • John Hodge (University of Leeds) Natural Se... more ... Session 3: Natural Selection as a Causal Theory • John Hodge (University of Leeds) Natural Selection: A Causal Theory • Robert Olby (Pittsburgh) Commentary • MeganDelehanty (Pittsburgh) Commentary • Workshop Participants ...

Research paper thumbnail of Polarized Th2 Cytokine Production in Patients with Hypertrophic Scar Following Thermal Injury

Polarized Th2 Cytokine Production in Patients with Hypertrophic Scar Following Thermal Injury

Http Dx Doi Org 10 1089 Jir 2006 26 179, Mar 16, 2006

Following thermal injury, hypertrophic scar (HSc) is a frequent and severe form of fibrosis of th... more Following thermal injury, hypertrophic scar (HSc) is a frequent and severe form of fibrosis of the skin, which limits movement and compromises the cosmetic appearance and function of the skin. Prolonged pruritus and dysesthesia are also common problems in the previously injured, fibrotic tissues, as current understanding of the pathogenesis is limited, and few effective therapies exist, as with other fibroproliferative disorders (FPD). To investigate the role of T cells and their cytokines in the development of HSc, intracellular cytokine synthesis of circulating T cells was measured serially in burn patients using flow cytometry from the time of injury to over a 1-year period during which many patients developed HSc. Within 1 month of injury, low interferon-gamma (IFN-gamma)-positive T cells (Th1) were found in association with low interleukin-12 (IL-12) and absent IFN-gamma cytokine levels in the serum. IL-4-positive Th 2 cells, however, were significantly increased compared with normal controls by 2 months postinjury. In burn patients with HSc, serum IL-10 and transforming growth factor-beta (TGF-beta) levels were also significantly increased early after burn injury in patients who later developed HSc compared with normal volunteers and with a subset of burn patients who did not develop HSc, before returning to normal levels after 6 months. Activated peripheral blood mononuclear cells (PBMC) demonstrated that mRNA for IFN-gamma was present only in normal volunteers or patients without HSc but was undetectable in HSc patients. IL-4 mRNA levels were increased in the PBMCs of burn patients with HSc. In HSc tissues, IL-4 mRNA was increased, whereas, IFN-gamma mRNA was reduced compared with normal skin and mature scar. Increased CD3(+) and CD4(+) cells were present in HSc tissues compared with normal skin and were coexpressed with the fibrogenic cytokine TGF-beta. These longitudinal studies in human patients with HSc suggest that fibrosis in the skin is associated with a polarized Th2 systemic response to injury that leads to increased T cells and their Th2 fibrogenic cytokines in tissues and the development of fibrosis and HSc.

Research paper thumbnail of Perceiving Causation via Videomicroscopy

Perceiving Causation via Videomicroscopy

Philosophy of Science, Dec 1, 2007

Research paper thumbnail of Why Images?

Research paper thumbnail of Fluorescent-activated cell-sorting analysis of intracellular interferon-γ and interleukin-4 in fresh and frozen human peripheral blood T-helper cells

Fluorescent-activated cell-sorting analysis of intracellular interferon-γ and interleukin-4 in fresh and frozen human peripheral blood T-helper cells

T-helper (Th) cells can be classified into at least three subsets based on their cytokine profile... more T-helper (Th) cells can be classified into at least three subsets based on their cytokine profiles: Th0, Th1, and Th2. The functional significance of each subset of Th cells can be determined in isolated human peripheral blood mononuclear cells (PBMC). Using two- or three-color cytometric detection of intracellular cytokines. These analyses have been limited by the requirement for fresh cells making sequential samples and longitudinal studies difficult. Cryopreservation of PBMC in liquid nitrogen for up to 1 year was evaluated to determine whether the Th1/Th2 ratio remained unchanged in cryopreserved lymphocytes. Aliquots of human PBMC from normal volunteers analyzed for activation using phorbol myristate acetate and evaluated using morphology showed that the surface marker expression was unchanged in fresh and frozen cells. Cytokine expression was measured using intracellular cytokine staining and three-color flow cytometric analysis. The percentages of cells producing interferon (IFN)-gamma or interleukin (IL)-4 were determined after 16 hours of phorbol myristate acetate and ionomycin stimulation in the presence of brefeldin A. No significant difference was found in cytokine production between fresh and frozen cells. The percentage of IFN-gamma and IL-4 producing CD3-positive fresh T cells was 19.2+/-5.8 percent and 0.9+/-0.4 percent vs. 17.6+/-0.75 percent and 0.9+/-0.3 percent, respectively, for frozen PBMC. The effects of thermal injury on the Th1/Th2 cytokine ratio and the development of hypertrophic scarring were then determined. Twelve burn patients examined 4 weeks postburn showed a significant shift in the Th1/Th2 ratio, compared with 13 normal human volunteers used as controls. IL-4 levels in the patient group were significantly higher than controls at 1 month postburn (12.7+/-2.6 percent vs. 3.9+/-0.5 percent, p<0.01) and IFN-gamma levels were significantly lower (9.3+/-1.7 percent vs. 15.3+/-2.3 percent, p<0.05). Thus, PBMC can be cryopreserved for up to 1 year, enabling investigation of chronologic changes in Th1/Th2 profiles. It is suggested that a "locked on" Th2 profile may contribute to the development of hypertrophic scarring after burn injury.

Research paper thumbnail of The effect of overexpression of activated rasB, rasC and rasS on Dictyostelium discoideum

Dictyostelium discoideum contains at least 5 ras genes. It had been previously demonstrated that ... more Dictyostelium discoideum contains at least 5 ras genes. It had been previously demonstrated that the expression of an activated rasG gene in D. discoideum resulted in cells which were unable to aggregate and a subset of which had a large, flattened morphology (Khosla et al, 1996. Mol. and Cell. Biol. 16: 4156-62). To investigate the role of the rasB, rasC, and rasS genes, an activating mutation (a glycine to threonine substitution at position 12) was made in each of the genes. The mutated genes were then expressed under the control of the inducible discoidin promoter. Overexpression of the rasC-G\2T and rasS-G\2T genes produced no evident abnormalities in cell morphology, growth, or development. Thus, rasC and rasS are not functionally equivalent to rasG, although no clues as to their roles in the cell were revealed. Overexpression of the ra.yf?-G12T gene resulted in the appearance of morphologically aberrent amoebae: a large proportion of the cells were large and flat with an incre...

Research paper thumbnail of Evelyn Fox Keller, Making Sense of Life: Explaining Biological Development with Models, Metaphors, and Machines . Cambridge, Mass.: Harvard University Press, 2002

Metascience, 2003

How have various forms of explanation-the models, metaphors, and machines of the subtitle-contrib... more How have various forms of explanation-the models, metaphors, and machines of the subtitle-contributed to biologists' understanding of development over the course of the last century? This book is not a philosophical work on explanation, and the reader expecting it to be one will be disappointed. Instead, it is a largely historical and, to some extent, sociological, survey of what has counted as an explanation, for whom and, in a limited way, why. While Keller makes passing reference to some standard philosophical concerns about explanation, this is not her focus. This might be taken to be a serious flaw in the book, but it must be acknowledged that she explicitly states that her goal is not to resolve extant questions about the nature of explanation, but rather to raise new questions. Furthermore, she describes her work here as "empirical rather than philosophical (at least in the strict sense of the term), and hence as complementing rather than supplementing more traditional work in the philosophy of explanation" (p. 5). The question, then, is whether she really does raise new questions and whether these questions open up new directions for inquiry into the nature of explanation? The book is divided into three sections. In the first, Keller explores several explanations of development that were developed in the first part of the twentieth century using mathematical or material models. (Model organisms are mentioned only in passing at the beginning of Chapter 2 and in the introduction to the second section of the book.) She focuses primarily on the work of Stéphane Leduc, D'Arcy Thompson, and Alan Turing and examines how the models developed by these men failed to exert any substantial influence on experimental biology, noting the existence of an epistemic divide between theoretical and experimental biology with early versions of a mathematical biology at this time falling clearly within the realm of the theoretical. These models were largely non

Research paper thumbnail of Emergent properties and the context objection to reduction

Emergent properties and the context objection to reduction

Biology & Philosophy, 2005

... the question of whether or not multiple realizability really does create insuperable difficul... more ... the question of whether or not multiple realizability really does create insuperable difficulties for ... Importantly, MDC do not limit satisfactory mechanisms to linearly orga-nized sequences. ... shows why under-standing mechanisms can help in the debate about reduction in biology. ...

Research paper thumbnail of Extending the mechanism: Dealing with the context objection to reduction

Research paper thumbnail of Empiricism and the Epistemic Status of Imaging Technologies

Research paper thumbnail of Polarized T Helper 2 Cell (TH2) Intracellular Cytokine Synthesis in Burn Patients with Hypertrophic Scarring

Polarized T Helper 2 Cell (TH2) Intracellular Cytokine Synthesis in Burn Patients with Hypertrophic Scarring

Journal of Burn Care & Rehabilitation, 2001

Research paper thumbnail of The changing landscape of the philosophy of medicine

The changing landscape of the philosophy of medicine

Philosophy Compass

Research paper thumbnail of Session 3: Natural selection as a causal theory

Session 3: Natural selection as a causal theory

... Session 3: Natural Selection as a Causal Theory • John Hodge (University of Leeds) Natural Se... more ... Session 3: Natural Selection as a Causal Theory • John Hodge (University of Leeds) Natural Selection: A Causal Theory • Robert Olby (Pittsburgh) Commentary • MeganDelehanty (Pittsburgh) Commentary • Workshop Participants ...

Research paper thumbnail of Polarized Th2 Cytokine Production in Patients with Hypertrophic Scar Following Thermal Injury

Polarized Th2 Cytokine Production in Patients with Hypertrophic Scar Following Thermal Injury

Http Dx Doi Org 10 1089 Jir 2006 26 179, Mar 16, 2006

Following thermal injury, hypertrophic scar (HSc) is a frequent and severe form of fibrosis of th... more Following thermal injury, hypertrophic scar (HSc) is a frequent and severe form of fibrosis of the skin, which limits movement and compromises the cosmetic appearance and function of the skin. Prolonged pruritus and dysesthesia are also common problems in the previously injured, fibrotic tissues, as current understanding of the pathogenesis is limited, and few effective therapies exist, as with other fibroproliferative disorders (FPD). To investigate the role of T cells and their cytokines in the development of HSc, intracellular cytokine synthesis of circulating T cells was measured serially in burn patients using flow cytometry from the time of injury to over a 1-year period during which many patients developed HSc. Within 1 month of injury, low interferon-gamma (IFN-gamma)-positive T cells (Th1) were found in association with low interleukin-12 (IL-12) and absent IFN-gamma cytokine levels in the serum. IL-4-positive Th 2 cells, however, were significantly increased compared with normal controls by 2 months postinjury. In burn patients with HSc, serum IL-10 and transforming growth factor-beta (TGF-beta) levels were also significantly increased early after burn injury in patients who later developed HSc compared with normal volunteers and with a subset of burn patients who did not develop HSc, before returning to normal levels after 6 months. Activated peripheral blood mononuclear cells (PBMC) demonstrated that mRNA for IFN-gamma was present only in normal volunteers or patients without HSc but was undetectable in HSc patients. IL-4 mRNA levels were increased in the PBMCs of burn patients with HSc. In HSc tissues, IL-4 mRNA was increased, whereas, IFN-gamma mRNA was reduced compared with normal skin and mature scar. Increased CD3(+) and CD4(+) cells were present in HSc tissues compared with normal skin and were coexpressed with the fibrogenic cytokine TGF-beta. These longitudinal studies in human patients with HSc suggest that fibrosis in the skin is associated with a polarized Th2 systemic response to injury that leads to increased T cells and their Th2 fibrogenic cytokines in tissues and the development of fibrosis and HSc.

Research paper thumbnail of Perceiving Causation via Videomicroscopy

Perceiving Causation via Videomicroscopy

Philosophy of Science, Dec 1, 2007

Research paper thumbnail of Why Images?

Research paper thumbnail of Fluorescent-activated cell-sorting analysis of intracellular interferon-γ and interleukin-4 in fresh and frozen human peripheral blood T-helper cells

Fluorescent-activated cell-sorting analysis of intracellular interferon-γ and interleukin-4 in fresh and frozen human peripheral blood T-helper cells

T-helper (Th) cells can be classified into at least three subsets based on their cytokine profile... more T-helper (Th) cells can be classified into at least three subsets based on their cytokine profiles: Th0, Th1, and Th2. The functional significance of each subset of Th cells can be determined in isolated human peripheral blood mononuclear cells (PBMC). Using two- or three-color cytometric detection of intracellular cytokines. These analyses have been limited by the requirement for fresh cells making sequential samples and longitudinal studies difficult. Cryopreservation of PBMC in liquid nitrogen for up to 1 year was evaluated to determine whether the Th1/Th2 ratio remained unchanged in cryopreserved lymphocytes. Aliquots of human PBMC from normal volunteers analyzed for activation using phorbol myristate acetate and evaluated using morphology showed that the surface marker expression was unchanged in fresh and frozen cells. Cytokine expression was measured using intracellular cytokine staining and three-color flow cytometric analysis. The percentages of cells producing interferon (IFN)-gamma or interleukin (IL)-4 were determined after 16 hours of phorbol myristate acetate and ionomycin stimulation in the presence of brefeldin A. No significant difference was found in cytokine production between fresh and frozen cells. The percentage of IFN-gamma and IL-4 producing CD3-positive fresh T cells was 19.2+/-5.8 percent and 0.9+/-0.4 percent vs. 17.6+/-0.75 percent and 0.9+/-0.3 percent, respectively, for frozen PBMC. The effects of thermal injury on the Th1/Th2 cytokine ratio and the development of hypertrophic scarring were then determined. Twelve burn patients examined 4 weeks postburn showed a significant shift in the Th1/Th2 ratio, compared with 13 normal human volunteers used as controls. IL-4 levels in the patient group were significantly higher than controls at 1 month postburn (12.7+/-2.6 percent vs. 3.9+/-0.5 percent, p<0.01) and IFN-gamma levels were significantly lower (9.3+/-1.7 percent vs. 15.3+/-2.3 percent, p<0.05). Thus, PBMC can be cryopreserved for up to 1 year, enabling investigation of chronologic changes in Th1/Th2 profiles. It is suggested that a "locked on" Th2 profile may contribute to the development of hypertrophic scarring after burn injury.