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Full-Text Articles in Medicine and Health Sciences

A Potential Synergistic Anticancer Effect Of Paclitaxel And Amifostine On Endometrial Cancer, Donghai Dai, A. Holmes, T. Nguyen, S. Davies, D. Theele, C. Verschraegen, Kimberly Leslie Apr 2013

A Potential Synergistic Anticancer Effect Of Paclitaxel And Amifostine On Endometrial Cancer, Donghai Dai, A. Holmes, T. Nguyen, S. Davies, D. Theele, C. Verschraegen, Kimberly Leslie

Donghai Dai

Although paclitaxel is one of the most effective chemotherapeutic agents, its usefulness is still limited in advanced and recurrent endometrial cancer. Amifostine protection of normal tissues against the side effects of chemotherapeutic agents has been clinically proven in cancer patients; however, its application in endometrial cancer has not been fully evaluated. We have investigated the use of paclitaxel and amifostine in controlling the growth of poorly differentiated endometrial cancer cells, Hec50co, in vitro and in vivo. Our studies show that amifostine had direct anticancer effects on endometrial cancer cells in vitro by arresting the cell cycle at the G1 phase …


Amifostine Enhancement Of The Anti-Cancer Effects Of Paclitaxel In Endometrial Cancer Is Tp53-Dependent, W. Luo, F. Wu, R. Elmaoued, B. Beck, E. Fischer, Xiangbing Meng, Kimberly Leslie, Donghai Dai Apr 2013

Amifostine Enhancement Of The Anti-Cancer Effects Of Paclitaxel In Endometrial Cancer Is Tp53-Dependent, W. Luo, F. Wu, R. Elmaoued, B. Beck, E. Fischer, Xiangbing Meng, Kimberly Leslie, Donghai Dai

Donghai Dai

Endometrial cancer (ECa) is the fourth most common malignancy in women. Currently, there is no effective therapy for advanced and recurrent cancer. Among the poor-outcome endometrial cancers, there is a high frequency of TP53 mutations. We have previously reported that amifostine has a direct anti-cancer effect and has a significant synergistic effect with paclitaxel when used in endometrial cancer cell and xenograft models. In this report, using a cell line with knock-down p53 expression through siRNA, we found that amifostine enhancement of paclitaxel's anticancer effect is p53 status-dependent. Amifostine promotes entry into the G2-M phase through regulation of cyclin-dependent kinase-1 …


A Therapeutic Model For Advanced Endometrial Cancer: Systemic Progestin In Combination With Local Adenoviral-Mediated Progesterone Receptor Expression, Donghai Dai, L. Albitar, T. Nguyen, L. Laidler, M. Singh, Kimberly Leslie Apr 2013

A Therapeutic Model For Advanced Endometrial Cancer: Systemic Progestin In Combination With Local Adenoviral-Mediated Progesterone Receptor Expression, Donghai Dai, L. Albitar, T. Nguyen, L. Laidler, M. Singh, Kimberly Leslie

Donghai Dai

Cancer of the uterine endometrium is a frequent gynecologic malignant disease for which few therapeutic options are available for advanced disease. Progesterone is the normal female hormone that limits growth and proliferation of endometrial cancers; however, progesterone receptors are frequently down-regulated, leading to treatment failures. The current studies explored the effectiveness of adenoviral-mediated progesterone receptor gene transduction in combination with progestin therapy in mouse xenograft models. Pretreatment of cells with progesterone receptor-encoding adenovirus and progestin inhibited the development of s.c. tumors in athymic mice. In the i.p. xenograft model, replacement of both isoforms of progesterone receptor, PRA and PRB, in …


Gestational Trophoblastic Diseases: 1. Pathophysiology Of Hyperglycosylated Hcg, L. Cole, Donghai Dai, S. Butler, Kimberly Leslie, E. Kohorn Apr 2013

Gestational Trophoblastic Diseases: 1. Pathophysiology Of Hyperglycosylated Hcg, L. Cole, Donghai Dai, S. Butler, Kimberly Leslie, E. Kohorn

Donghai Dai

OBJECTIVE: Hyperglycosylated hCG (hCG-H) is a glycosylation variant of hCG produced by cytotrophoblast cells at implantation of pregnancy and in choriocarcinoma. We investigated the biological function of hCG-H in invasion in vitro and in vivo and the use of hCG-H antibodies in blocking tumorigenesis and cancer growth in vivo. METHODS AND RESULTS: hCG-H accounts for 43% to 100% of total hCG immunoreactivity in the culture fluid of choriocarcinoma cell lines and 100% in primary cultures of pregnancy cytotrophoblast cells. We investigated the action of hCG and hCG-H on isolated cytotrophoblast cell primary cultures and on 3 different lines of choriocarcinoma …


The Nitric Oxide-Cyclic Gmp Pathway Plays An Essential Role In Both Promoting Cell Survival Of Cerebellar Granule Cells In Culture And Protecting The Cells Against Ethanol Neurotoxicity, N. Pantazis, J. West, Donghai Dai Apr 2013

The Nitric Oxide-Cyclic Gmp Pathway Plays An Essential Role In Both Promoting Cell Survival Of Cerebellar Granule Cells In Culture And Protecting The Cells Against Ethanol Neurotoxicity, N. Pantazis, J. West, Donghai Dai

Donghai Dai

NMDA has two beneficial effects on primary neuronal cultures of cerebellar granule cells (CGCs) established from 10-day-old rat pups. First, NMDA is neurotrophic and will enhance survival of CGCs in culture in the absence of ethanol. Second, ethanol exposure will induce cell death in CGC cultures, and NMDA can lessen this ethanol-induced cell loss, i.e., NMDA is neuroprotective. Because NMDA can stimulate production of nitric oxide (NO), which can in turn enhance synthesis of cyclic GMP, this study tested the hypothesis that the NO-cyclic GMP pathway is essential for NMDA-mediated neurotrophism and neuroprotection. Inhibiting the synthesis of NO with N(G)-nitro-L-arginine …


Mrna Expression In Rabbit Experimental Aneurysms: A Study Using Gene Chip Microarrays, W. Mangrum, F. Farassati, R. Kadirvel, C. Kolbert, S. Raghavakaimal, Donghai Dai, Y. Ding, D. Grill, V. Khurana, D. Kallmes Apr 2013

Mrna Expression In Rabbit Experimental Aneurysms: A Study Using Gene Chip Microarrays, W. Mangrum, F. Farassati, R. Kadirvel, C. Kolbert, S. Raghavakaimal, Donghai Dai, Y. Ding, D. Grill, V. Khurana, D. Kallmes

Donghai Dai

BACKGROUND AND PURPOSE: The molecular characteristics of intracranial aneurysms are still poorly documented. A rabbit elastase aneurysm model has been helpful in the evaluation of devices and strategies involved in endovascular treatment of aneurysms. The goal of this project was to document the molecular changes, assessed by gene chip microarrays, associated with the creation of aneurysms in this model compared with the contralateral carotid artery. MATERIALS AND METHODS: A microarray of rabbit genes of interest was constructed using rabbit nucleotide sequences from GenBank. Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 4 rabbits. …


Transfection Of C6 Glioma Cells With Glia Maturation Factor Upregulates Brain-Derived Neurotrophic Factor And Nerve Growth Factor: Trophic Effects And Protection Against Ethanol Toxicity In Cerebellar Granule Cells, N. Pantazis, A. Zaheer, Donghai Dai, S. Zaheer, S. Green, R. Lim Apr 2013

Transfection Of C6 Glioma Cells With Glia Maturation Factor Upregulates Brain-Derived Neurotrophic Factor And Nerve Growth Factor: Trophic Effects And Protection Against Ethanol Toxicity In Cerebellar Granule Cells, N. Pantazis, A. Zaheer, Donghai Dai, S. Zaheer, S. Green, R. Lim

Donghai Dai

Glial cells play active roles in neuronal survival, as well as neuroprotection against toxic insult. Recent studies suggest that the brain protein glia maturation factor (GMF) is involved in intracellular signaling in glia. This study investigated whether or not GMF plays a role in the survival-promoting and neuroprotective functions of glia. C6 glioma cells were transfected in vitro with GMF utilizing an adenovirus vector. The transfected cells overexpressed GMF intracellularly, but did not secrete the protein. The conditioned medium (CM) was obtained from the GMF-transfected cells (CM-GMF) and tested on primary neuronal cultures, consisting of cerebellar granule cells (CGC). The …


Preclinical Development Of A Neutral, Estrogen Receptor-Targeted, Tridentate 99mtc(I)-Estradiol-Pyridin-2-Yl Hydrazine Derivative For Imaging Of Breast And Endometrial Cancers, T. Nayak, H. Hathaway, C. Ramesh, J. Arterburn, Donghai Dai, L. Sklar, J. Norenberg, E. Prossnitz Apr 2013

Preclinical Development Of A Neutral, Estrogen Receptor-Targeted, Tridentate 99mtc(I)-Estradiol-Pyridin-2-Yl Hydrazine Derivative For Imaging Of Breast And Endometrial Cancers, T. Nayak, H. Hathaway, C. Ramesh, J. Arterburn, Donghai Dai, L. Sklar, J. Norenberg, E. Prossnitz

Donghai Dai

Breast and endometrial cancers are the most common invasive malignancies in women, with more than 217,000 new diagnoses per year in the United States. These cancers are often classified into 2 subtypes based on the expression of the classical estrogen receptor. In this study, we describe a new structural class of neutral tridentate 99mTc(I)-estradiol-pyridin-2-yl hydrazine derivatives for potential use in breast and endometrial cancer imaging. METHODS: The 99mTc(I)-estradiol-pyridin-2-yl hydrazine derivative was synthesized via the Sonogashira cross-coupling reaction and radiolabeled via the tricarbonyl approach. Radiochemical purity was assessed by high-performance liquid chromatography. Cell-binding studies were performed with human breast adenocarcinoma MCF-7 …


Fgf-2, Ngf And Igf-1, But Not Bdnf, Utilize A Nitric Oxide Pathway To Signal Neurotrophic And Neuroprotective Effects Against Alcohol Toxicity In Cerebellar Granule Cell Cultures, D. Bonthius, B. Karacay, Donghai Dai, N. Pantazis Apr 2013

Fgf-2, Ngf And Igf-1, But Not Bdnf, Utilize A Nitric Oxide Pathway To Signal Neurotrophic And Neuroprotective Effects Against Alcohol Toxicity In Cerebellar Granule Cell Cultures, D. Bonthius, B. Karacay, Donghai Dai, N. Pantazis

Donghai Dai

Neuronal death is a prominent neuropathological component of fetal alcohol syndrome (FAS). Identification of molecular agents and pathways that can ameliorate alcohol-induced cell loss offers possible therapeutic strategies for FAS and potential insight into its pathogenesis. This study investigated the effects of growth factors on cellular survival in alcohol-exposed cerebellar granule cell (CGC) cultures and examined the role of the nitric oxide (NO)-cGMP-PKG (cGMP-dependent protein kinase) pathway in the cell survival-promoting effects of these growth factors. Primary CGC cultures were exposed to 0 or 400 mg/dl ethanol, accompanied by either no growth factor or 30 ng/ml fibroblast growth factor-2 (FGF-2), …


Gestational Trophoblastic Diseases: 1. Pathophysiology Of Hyperglycosylated Hcg, L. A. Cole, Donghai Dai, S. A. Butler, K. K. Leslie, E. I. Kohorn Apr 2013

Gestational Trophoblastic Diseases: 1. Pathophysiology Of Hyperglycosylated Hcg, L. A. Cole, Donghai Dai, S. A. Butler, K. K. Leslie, E. I. Kohorn

Donghai Dai

OBJECTIVE: Hyperglycosylated hCG (hCG-H) is a glycosylation variant of hCG produced by cytotrophoblast cells at implantation of pregnancy and in choriocarcinoma. We investigated the biological function of hCG-H in invasion in vitro and in vivo and the use of hCG-H antibodies in blocking tumorigenesis and cancer growth in vivo. METHODS AND RESULTS: hCG-H accounts for 43% to 100% of total hCG immunoreactivity in the culture fluid of choriocarcinoma cell lines and 100% in primary cultures of pregnancy cytotrophoblast cells. We investigated the action of hCG and hCG-H on isolated cytotrophoblast cell primary cultures and on 3 different lines of choriocarcinoma …


Effects Of Bevacizumab In Mouse Model Of Endometrial Cancer: Defining The Molecular Basis For Resistance, S. Davies, Donghai Dai, G. Pickett, K. Thiel, V. Korovkina, Kimberly Leslie Feb 2013

Effects Of Bevacizumab In Mouse Model Of Endometrial Cancer: Defining The Molecular Basis For Resistance, S. Davies, Donghai Dai, G. Pickett, K. Thiel, V. Korovkina, Kimberly Leslie

Kimberly K. Leslie

Endometrial cancer is the most frequent gynecologic cancer in women. Long-term outcomes for patients with advanced stage or recurrent disease are poor. Targeted molecular therapy against the vascular endothelial growth factor (VEGF) and its receptors constitute a new therapeutic option for these patients. The goal of our study was to assess the potential effectiveness of inhibition of VEGF/VEGFR signaling in a xenograft model of endometrial cancer using bevacizumab (Avastin, a humanized antibody against VEGFA). We also aimed to identify molecular markers of sensitivity or resistance to this agent. We show that bevacizumab retards tumor growth in athymic mice by inhibiting …


Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie Feb 2013

Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie

Kimberly K. Leslie

Overexpression of metadherin (MTDH) has been documented in many solid tumors and is implicated in metastasis and chemoresistance. MTDH has been detected at the plasma membrane as well as in the cytoplasm and nucleus, and the function of MTDH in these locales remains under investigation. In the nucleus, MTDH acts as a transcription co-factor to induce expression of chemoresistance-associated genes. However, MTDH is predominantly cytoplasmic in prostate tumors, and this localization correlates with poor prognosis. Herein, we used endometrial cancer cells as a model system to define a new role for MTDH in the cytoplasm. First, MTDH was primarily localized …


A Potential Synergistic Anticancer Effect Of Paclitaxel And Amifostine On Endometrial Cancer, Donghai Dai, A. Holmes, T. Nguyen, S. Davies, D. Theele, C. Verschraegen, Kimberly Leslie Feb 2013

A Potential Synergistic Anticancer Effect Of Paclitaxel And Amifostine On Endometrial Cancer, Donghai Dai, A. Holmes, T. Nguyen, S. Davies, D. Theele, C. Verschraegen, Kimberly Leslie

Kimberly K. Leslie

Although paclitaxel is one of the most effective chemotherapeutic agents, its usefulness is still limited in advanced and recurrent endometrial cancer. Amifostine protection of normal tissues against the side effects of chemotherapeutic agents has been clinically proven in cancer patients; however, its application in endometrial cancer has not been fully evaluated. We have investigated the use of paclitaxel and amifostine in controlling the growth of poorly differentiated endometrial cancer cells, Hec50co, in vitro and in vivo. Our studies show that amifostine had direct anticancer effects on endometrial cancer cells in vitro by arresting the cell cycle at the G1 phase …


Gestational Trophoblastic Diseases: 1. Pathophysiology Of Hyperglycosylated Hcg, L. Cole, Donghai Dai, S. Butler, Kimberly Leslie, E. Kohorn Feb 2013

Gestational Trophoblastic Diseases: 1. Pathophysiology Of Hyperglycosylated Hcg, L. Cole, Donghai Dai, S. Butler, Kimberly Leslie, E. Kohorn

Kimberly K. Leslie

OBJECTIVE: Hyperglycosylated hCG (hCG-H) is a glycosylation variant of hCG produced by cytotrophoblast cells at implantation of pregnancy and in choriocarcinoma. We investigated the biological function of hCG-H in invasion in vitro and in vivo and the use of hCG-H antibodies in blocking tumorigenesis and cancer growth in vivo. METHODS AND RESULTS: hCG-H accounts for 43% to 100% of total hCG immunoreactivity in the culture fluid of choriocarcinoma cell lines and 100% in primary cultures of pregnancy cytotrophoblast cells. We investigated the action of hCG and hCG-H on isolated cytotrophoblast cell primary cultures and on 3 different lines of choriocarcinoma …


Chronic Intrauterine Infection And Inflammation In The Preterm Rabbit, Despite Antibiotic Therapy, R. Gibbs, J. Davies, R. Mcduffie, Kimberly Leslie, M. Sherman, C. Centretto, D. Wolf Feb 2013

Chronic Intrauterine Infection And Inflammation In The Preterm Rabbit, Despite Antibiotic Therapy, R. Gibbs, J. Davies, R. Mcduffie, Kimberly Leslie, M. Sherman, C. Centretto, D. Wolf

Kimberly K. Leslie

OBJECTIVE: In a pregnant rabbit model using intracervical inoculation of Escherichia coli with delayed antibiotic therapy, we investigated the rate of positive cultures and histologic inflammation of maternal and fetal compartments and the concentration of tumor necrosis factor-alpha in the amniotic fluid for up to 5 days. STUDY DESIGN: New Zealand White rabbits at 70% gestation were inoculated intracervically with 10(3) - 10(4) colony-forming units of E coli per uterine horn. At varying intervals after inoculation (0.5 - 4.0 hours), antibiotic therapy was initiated with ampicillin-sulbactam. Primary outcomes were positive cultures and histologic inflammation score. Tumor necrosis factor-alpha levels in …


Oral Contraceptives And Skin Cancer: Is There A Link?, Kimberly Leslie, E. Espey Feb 2013

Oral Contraceptives And Skin Cancer: Is There A Link?, Kimberly Leslie, E. Espey

Kimberly K. Leslie

The skin expresses estrogen, progesterone, and androgen receptors. In the presence of steroid hormones, such as those contained in oral contraceptives, the skin likely responds to hormonal signals that control the cell cycle, apoptosis, DNA replication, and other cellular functions. Some estrogen-responsive pathways have the potential to promote tumor development, including the augmentation of epidermal growth factor signaling, the expression of proto-oncogenes, and inhibition of apoptosis. The question of whether oral contraceptives increase the risk for the development of skin cancer, particularly melanoma, is still an area of concern. This paper reviews the available evidence, the bulk of which suggests …


Amifostine Enhancement Of The Anti-Cancer Effects Of Paclitaxel In Endometrial Cancer Is Tp53-Dependent, W. Luo, F. Wu, R. Elmaoued, B. Beck, E. Fischer, Xiangbing Meng, Kimberly Leslie, Donghai Dai Feb 2013

Amifostine Enhancement Of The Anti-Cancer Effects Of Paclitaxel In Endometrial Cancer Is Tp53-Dependent, W. Luo, F. Wu, R. Elmaoued, B. Beck, E. Fischer, Xiangbing Meng, Kimberly Leslie, Donghai Dai

Kimberly K. Leslie

Endometrial cancer (ECa) is the fourth most common malignancy in women. Currently, there is no effective therapy for advanced and recurrent cancer. Among the poor-outcome endometrial cancers, there is a high frequency of TP53 mutations. We have previously reported that amifostine has a direct anti-cancer effect and has a significant synergistic effect with paclitaxel when used in endometrial cancer cell and xenograft models. In this report, using a cell line with knock-down p53 expression through siRNA, we found that amifostine enhancement of paclitaxel's anticancer effect is p53 status-dependent. Amifostine promotes entry into the G2-M phase through regulation of cyclin-dependent kinase-1 …


Pdgf-Ralpha Gene Expression Predicts Proliferation, But Pdgf-A Suppresses Transdifferentiation Of Neonatal Mouse Lung Myofibroblasts, P. Kimani, A. Holmes, Ruth Grossmann, S. Mcgowan Sep 2012

Pdgf-Ralpha Gene Expression Predicts Proliferation, But Pdgf-A Suppresses Transdifferentiation Of Neonatal Mouse Lung Myofibroblasts, P. Kimani, A. Holmes, Ruth Grossmann, S. Mcgowan

Ruth E. Grossmann

BACKGROUND: Platelet-derived growth factor A (PDGF-A) signals solely through PDGF-Ralpha, and is required for fibroblast proliferation and transdifferentiation (fibroblast to myofibroblast conversion) during alveolar development, because pdgfa-null mice lack both myofibroblasts and alveoli. However, these PDGF-A-mediated mechanisms remain incompletely defined. At postnatal days 4 and 12 (P4 and P12), using mouse lung fibroblasts, we examined (a) how PDGF-Ralpha correlates with ki67 (proliferation marker) or alpha-smooth muscle actin (alphaSMA, myofibroblast marker) expression, and (b) whether PDGF-A directly affects alphaSMA or modifies stimulation by transforming growth factor beta (TGFbeta). METHODS: Using flow cytometry we examined PDGF-Ralpha, alphaSMA and Ki67 in mice which …


Effectiveness Of Transcutaneous Electrical Nerve Stimulation For Treatment Of Hyperalgesia And Pain, J. Desantana, D. Walsh, C. Vance, Barbara Rakel, K. Sluka May 2012

Effectiveness Of Transcutaneous Electrical Nerve Stimulation For Treatment Of Hyperalgesia And Pain, J. Desantana, D. Walsh, C. Vance, Barbara Rakel, K. Sluka

Barbara A. Rakel

Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacologic treatment for pain relief. TENS has been used to treat a variety of painful conditions. This review updates the basic and clinical science regarding the use of TENS that has been published in the past 3 years (ie, 2005-2008). Basic science studies using animal models of inflammation show changes in the peripheral nervous system, as well as in the spinal cord and descending inhibitory pathways, in response to TENS. Translational studies show mechanisms to prevent analgesic tolerance to repeated application of TENS. This review also highlights data from recent randomized, placebo-controlled trials …


The Influence Of Second Intermediate Host Dispersion Pattern Upon The Transmission Of Cercariae Of Echinoparyphium Recurvatum (Digenea: Echinostomatidae), Ann Mccarthy Mar 2012

The Influence Of Second Intermediate Host Dispersion Pattern Upon The Transmission Of Cercariae Of Echinoparyphium Recurvatum (Digenea: Echinostomatidae), Ann Mccarthy

Ann Marie McCarthy

Transmission of cercariae of the echinostome digenean Echinoparyphium recurvatum was observed in experimental populations of the second intermediate host snail Lymnaea peregra. Populations of 100 snails were distributed among plastic mesh cages in an infection arena to produce different patterns of host dispersion. Cercarial transmission was investigated in host populations showing three separate patterns of host dispersion; Ideal Regular, Random and Contagious ('Clumped'). Levels of cercarial transmission in populations showing each type of dispersion pattern were found to be significantly different. The highest rate of cercarial transmission occurred in the contagiously dispersed host population, and the lowest in the randomly …


Speciation Of Echinostomes: Evidence For The Existence Of Two Sympatric Sibling Species In The Complex Echinoparyphium Recurvatum (Von Linstow 1873) (Digenea: Echinostomatidae), Ann Mccarthy Mar 2012

Speciation Of Echinostomes: Evidence For The Existence Of Two Sympatric Sibling Species In The Complex Echinoparyphium Recurvatum (Von Linstow 1873) (Digenea: Echinostomatidae), Ann Mccarthy

Ann Marie McCarthy

Evidence for the existence of 2 first intermediate host-specific sibling species of the 45 collar-spined echinostome Echinoparyphium recurvatum is presented. Experimental studies on their life-cycles were carried out under controlled laboratory conditions. The two entities were found to be morphologically indistinguishable in all major respects, yet they exhibited distinct biological characteristics. One of the sibling species utilizes the freshwater lymnaeid pulmonate snail Lymnaea peregra as first intermediate host, and the adults occur in the anterior small intestine of the wildfowl experimental definitive host Anas platyrhynchos. The other utilizes the freshwater mesogastropod prosobranch snail Valvata piscinalis as first intermediate host, and …


Agricultural Health In The Gambia I: Agricultural Practices And Developments, R. Kuye, K. Donham, S. Marquez, W. Sanderson, L. Fuortes, R. Rautiainen, M. Jones, Kennith R. Culp Mar 2012

Agricultural Health In The Gambia I: Agricultural Practices And Developments, R. Kuye, K. Donham, S. Marquez, W. Sanderson, L. Fuortes, R. Rautiainen, M. Jones, Kennith R. Culp

Kennith R. Culp

This manuscript reports results of our study to characterize the historical developments of agricultural practices in The Gambia and related health risks of farm workers. It surveys the various factors that shape production agriculture in the country and examines the degrees to which hand tools, animal traction, motorized traction and manual labour all contribute to the inherent hazards of farm work. The principal objective of this study is to lay the ground work for detailed research of occupational health hazards in Gambian agriculture; and development of policies and programmes to promote the health of Gambian farmers. The authors of this …


The Enzymes Of Lactose Biosynthesis. I. Purification And Properties Of Udpg Pyrophosphorylase From Bovine Mammary Tissue, Victoria Steelman, K. Ebner Nov 2011

The Enzymes Of Lactose Biosynthesis. I. Purification And Properties Of Udpg Pyrophosphorylase From Bovine Mammary Tissue, Victoria Steelman, K. Ebner

Victoria J. Steelman

No abstract provided.


Hexosamine Biosynthesis Pathway Flux Contributes To Insulin Resistance Via Altering Membrane Phosphatidylinositol 4,5-Bisphosphate And Cortical Filamentous Actin, P. Bhonagiri, G. R. Pattar, E. M. Horvath, K. M. Habegger, Ann Mccarthy, J. S. Elmendorf Oct 2011

Hexosamine Biosynthesis Pathway Flux Contributes To Insulin Resistance Via Altering Membrane Phosphatidylinositol 4,5-Bisphosphate And Cortical Filamentous Actin, P. Bhonagiri, G. R. Pattar, E. M. Horvath, K. M. Habegger, Ann Mccarthy, J. S. Elmendorf

Ann Marie McCarthy

We recently found that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP(2))-regulated filamentous actin (F-actin) polymerization was diminished in hyperinsulinemic cell culture models of insulin resistance. Here we delineated whether increased glucose flux through the hexosamine biosynthesis pathway (HBP) causes the PIP(2)/F-actin dysregulation and insulin resistance induced by hyperinsulinemia. Increased HBP activity was detected in 3T3-L1 adipocytes cultured under conditions closely resembling physiological hyperinsulinemia (5 nm insulin for 12 h) and in cells where HBP activity was amplified by 2 mm glucosamine (GlcN). Both the physiological hyperinsulinemia and experimental GlcN challenge induced comparable losses of PIP(2) and F-actin. In addition to protecting against …


A Policy Change Strategy For Head Lice Management, K. Andresen, Ann Mccarthy Oct 2011

A Policy Change Strategy For Head Lice Management, K. Andresen, Ann Mccarthy

Ann Marie McCarthy

The purpose of this project was to formulate an effective change strategy for head lice management in a group of five separate school districts within one county. Despite a desire to use evidence to support their practice, school nurses often encounter educational system barriers that prevent independent management of health conditions. The use of collaborative community relationships, identification of underlying hierarchy structures in school policy development, and targeted system education were the catalysts for changing beliefs and ultimately policy within these school districts. The focus of this project was to develop a policy change strategy for head lice. The strategy …


Agricultural Health In The Gambia I: Agricultural Practices And Developments, R. Kuye, K. Donham, S. Marquez, W. Sanderson, L. Fuortes, R. Rautiainen, M. Jones, Kennith R. Culp Oct 2011

Agricultural Health In The Gambia I: Agricultural Practices And Developments, R. Kuye, K. Donham, S. Marquez, W. Sanderson, L. Fuortes, R. Rautiainen, M. Jones, Kennith R. Culp

Kennith R. Culp

This manuscript reports results of our study to characterize the historical developments of agricultural practices in The Gambia and related health risks of farm workers. It surveys the various factors that shape production agriculture in the country and examines the degrees to which hand tools, animal traction, motorized traction and manual labour all contribute to the inherent hazards of farm work. The principal objective of this study is to lay the ground work for detailed research of occupational health hazards in Gambian agriculture; and development of policies and programmes to promote the health of Gambian farmers. The authors of this …


A Novel Homeobox Gene Pitx3 Is Mutated In Families With Autosomal-Dominant Cataracts And Asmd, E. Semina, R. Ferrell, H. Mintz-Hittner, P. Bitoun, W. Alward, R. Reiter, C. Funkhauser, Sandra Daack-Hirsch, J. Murray Oct 2011

A Novel Homeobox Gene Pitx3 Is Mutated In Families With Autosomal-Dominant Cataracts And Asmd, E. Semina, R. Ferrell, H. Mintz-Hittner, P. Bitoun, W. Alward, R. Reiter, C. Funkhauser, Sandra Daack-Hirsch, J. Murray

Sandra Daack-Hirsch

We report here the identification of a new human homeobox gene, PITX3, and its involvement in anterior segment mesenchymal dysgenesis (ASMD) and congenital cataracts in humans. The PITX3 gene is the human homologue of the mouse Pitx3 gene and is a member of the RIEG/PITX homeobox gene family. The protein encoded by PITX3 shows 99% amino-acid identity to the mouse protein, with 100% identity in the homeodomain and approximately 70% overall identity to other members of this family. We mapped the human PITX3 gene to 10q25 using a radiation-hybrid panel. A collection of 80 DNA samples from individuals with various …


Impaired Fgf Signaling Contributes To Cleft Lip And Palate, B. Riley, M. Mansilla, J. Ma, Sandra Daack-Hirsch, B. Maher, L. Raffensperger, E. Russo, A. Vieira, C. Dode, M. Mohammadi, M. Marazita, J. Murray Oct 2011

Impaired Fgf Signaling Contributes To Cleft Lip And Palate, B. Riley, M. Mansilla, J. Ma, Sandra Daack-Hirsch, B. Maher, L. Raffensperger, E. Russo, A. Vieira, C. Dode, M. Mohammadi, M. Marazita, J. Murray

Sandra Daack-Hirsch

Nonsyndromic cleft lip and palate (NS CLP) is a complex birth defect resulting from a combination of genetic and environmental factors. Several members of the FGF and FGFR families are expressed during craniofacial development and can rarely harbor mutations that result in human clefting syndromes. We hypothesized that disruptions in this pathway might also contribute to NS CLP. We sequenced the coding regions and performed association testing on 12 genes (FGFR1, FGFR2, FGFR3, FGF2, FGF3, FGF4, FGF7, FGF8, FGF9, FGF10, FGF18, and NUDT6) and used protein structure analyses to predict the function of amino acid variants. Seven likely disease-causing mutations …


Characterization Of A Novel Gene Disrupted By A Balanced Chromosomal Translocation T(2;19)(Q11.2;Q13.3) In A Family With Cleft Lip And Palate, K. Yoshiura, J. Machida, Sandra Daack-Hirsch, S. Patil, L. Ashworth, J. Hecht, J. Murray Oct 2011

Characterization Of A Novel Gene Disrupted By A Balanced Chromosomal Translocation T(2;19)(Q11.2;Q13.3) In A Family With Cleft Lip And Palate, K. Yoshiura, J. Machida, Sandra Daack-Hirsch, S. Patil, L. Ashworth, J. Hecht, J. Murray

Sandra Daack-Hirsch

Cleft lip with or without cleft palate is a common birth defect that is genetically complex. The nonsyndromic forms have been studied genetically using linkage and candidate-gene association studies with only partial success in defining the loci responsible for orofacial clefting. Loci for nonsyndromic cases have been suggested on 2p13, 4q31, 6p24, 17q21-q24, and 19q13.2. Recently, we identified a family in which cleft lip and palate segregated in two of three generations with a balanced chromosomal translocation t(2;19)(q11. 2;q13.3). We used a positional-cloning strategy to identify a novel gene disrupted by the translocation on chromosome 19. Eight rare (q 0.01) …


Complete Sequencing Shows A Role For Msx1 In Non-Syndromic Cleft Lip And Palate, P. A. Jezewski, A. R. Vieira, C. Nishimura, B. Ludwig, M. Johnson, S. E. O'Brien, Sandra Daack-Hirsch, R. E. Schultz, A. Weber, B. Nepomucena, P. A. Romitti, K. Christensen, I. M. Orioli, E. E. Castilla, J. Machida, N. Natsume, J. C. Murray Oct 2011

Complete Sequencing Shows A Role For Msx1 In Non-Syndromic Cleft Lip And Palate, P. A. Jezewski, A. R. Vieira, C. Nishimura, B. Ludwig, M. Johnson, S. E. O'Brien, Sandra Daack-Hirsch, R. E. Schultz, A. Weber, B. Nepomucena, P. A. Romitti, K. Christensen, I. M. Orioli, E. E. Castilla, J. Machida, N. Natsume, J. C. Murray

Sandra Daack-Hirsch

MSX1 has been proposed as a gene in which mutations may contribute to non-syndromic forms of cleft lip and/or cleft palate. Support for this comes from human linkage and linkage disequilibrium studies, chromosomal deletions resulting in haploinsufficiency, a large family with a stop codon mutation that includes clefting as a phenotype, and the Msx1 phenotype in a knockout mouse. This report describes a population based scan for mutations encompassing the sense and antisense transcribed sequence of MSX1 (two exons, one intron). We compare the completed genomic sequence of MSX1 to the mouse Msx1 sequence to identify non-coding homology regions, and …