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Full-Text Articles in Medicine and Health Sciences
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
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
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
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), …
Relative Contribution Of Nedd4 And Nedd4-2 To Enac Regulation In Epithelia Determined By Rna Interference., Peter Snyder, Jennifer Steines, Diane Olson
Relative Contribution Of Nedd4 And Nedd4-2 To Enac Regulation In Epithelia Determined By Rna Interference., Peter Snyder, Jennifer Steines, Diane Olson
Jennifer C. Steines Wagemester
Epithelial Na+ transport is regulated in large part by mechanisms that control expression of the epithelial Na+ channel (ENaC) at the cell surface. Nedd4 and Nedd4-2 are candidates to control ENaC surface expression, but it is not known which of these proteins contributes to ENaC regulation in epithelia. To address this question, we used RNA interference to selectively reduce expression of Nedd4 or Nedd4-2. We found that endogenous Nedd4-2, but not Nedd4, negatively regulates ENaC in two epithelial cell lines (Fischer rat thyroid and H441); small interfering RNA (siRNA) against Nedd4-2 increased amiloride-sensitive Na+ current (compared with control siRNA), but …
Camp And Serum And Glucocorticoid-Inducible Kinase (Sgk) Regulate The Epithelial Na(+) Channel Through Convergent Phosphorylation Of Nedd4-2., Peter Snyder, Diane Olson, Rajesh Kabra, Ruifeng Zhou, Jennifer Steines
Camp And Serum And Glucocorticoid-Inducible Kinase (Sgk) Regulate The Epithelial Na(+) Channel Through Convergent Phosphorylation Of Nedd4-2., Peter Snyder, Diane Olson, Rajesh Kabra, Ruifeng Zhou, Jennifer Steines
Jennifer C. Steines Wagemester
The epithelial Na(+) channel (ENaC) functions as a pathway for epithelial Na(+) transport, contributing to Na(+) homeostasis and blood pressure control. Vasopressin increases ENaC expression at the cell surface through a pathway that includes cAMP and cAMP-dependent protein kinase (PKA), but the mechanisms that link PKA to ENaC are unknown. Here we found that cAMP regulates Na(+) transport in part by inhibiting the function of Nedd4-2, an E3 ubiquitin-protein ligase that targets ENaC for degradation. Consistent with this model, we found that cAMP inhibited Nedd4-2 by decreasing its binding to ENaC. Moreover, decreased Nedd4-2 expression (RNA interference) or overexpression of …
The Effect Of A Novel Glycoprotein Iib/Iiia Antagonist, Sr 121566a, On Platelet Aggregation And Activation In Rhesus Monkeys., Mark Santillan, J. Herring, D. Hoppensteadt, W. Jeske, J. Herbert, J. Fareed
The Effect Of A Novel Glycoprotein Iib/Iiia Antagonist, Sr 121566a, On Platelet Aggregation And Activation In Rhesus Monkeys., Mark Santillan, J. Herring, D. Hoppensteadt, W. Jeske, J. Herbert, J. Fareed
Mark K. Santillan
SR 121566A represents a peptidomimetic glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor 3-[N- 4-[4-(aminoiminomethyl)phenyl]-1,3-thiazol-2-yl ) -N-(1-carboxymethylpiperid-4-yl) amino] propionic acid, trihydrochloride. To investigate the intravenous and subcutaneous pharmacodynamics of this agent, a primate model ( Macaca mulatta) was used. The IC50 for adenosine diphosphate (ADP) (10 micromol/L)-induced platelet aggregation in this primate platelet system was found to be 45 +/- 6 nmol/L. Comparatively in the human platelet rich plasma system, SR 121566A demonstrated an IC50 of 39 +/- 4 nmol/L. Graded doses of SR 121566A in the range of 25-400 microg/kg were administered intravenously. Blood samples were drawn from individual groups of primates …
From Molecules To Medicine: A Future Cure For Preeclampsia?, Mark Santillan, Donna Santillan, Curt Sigmund, Stephen Hunter
From Molecules To Medicine: A Future Cure For Preeclampsia?, Mark Santillan, Donna Santillan, Curt Sigmund, Stephen Hunter
Mark K. Santillan
In the United States, preeclampsia (PreE) affects 5-7% of all pregnancies, yet represents 15% of all maternal-fetal morbidity and mortality. PreE causes fetal growth restriction, oligohydramnios, fetal death, and maternal seizures, stroke, cerebrovascular hemorrhage and death. It has immediate and potentially long-term effects on both the fetus and mother. To date, the molecular pathogenesis of PreE is largely unknown. Multiple pathways, including dysfunctional angiogenesis, inappropriate placentation, oxidative stress and an altered immunological milieu have been proposed as key players in the development of PreE. In addition, genetic factors in all of these pathways are essential components in the etiology of …
Acute Intrauterine Infection Results In An Imbalance Between Pro- And Anti-Inflammatory Cytokines In The Pregnant Rabbit., Kimberly Leslie, S. Lee, S. Woodcock, J. Davies, R. Mcduffie, E. Hirsch, M. Sherman, J. Eskens, R. Gibbs
Acute Intrauterine Infection Results In An Imbalance Between Pro- And Anti-Inflammatory Cytokines In The Pregnant Rabbit., Kimberly Leslie, S. Lee, S. Woodcock, J. Davies, R. Mcduffie, E. Hirsch, M. Sherman, J. Eskens, R. Gibbs
Kimberly K. Leslie
PROBLEM: Intrauterine infection results in an increase in cytokines. This study compared the time courses for the pro- and anti-inflammatory cytokine responses in 33 pregnant rabbits at 70% gestation. Pro-inflammatory markers were activated nuclear factor-kappa B (NF-kappaB) in placenta and tumor necrosis factor-alpha (TNF-alpha) in amniotic fluid. These were compared to the anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), in placenta and uterus. METHOD OF STUDY: Does were endoscopically inoculated with Escherichia coli through their cervices and sacrificed at six intervals between 0 and 30 hr post-inoculation. RESULTS: Activated NF-kappaB, determined by electromobility gel shift assay, increased significantly 16 hr after …
Histologic Inflammation In The Maternal And Fetal Compartments In A Rabbit Model Of Acute Intra-Amniotic Infection., J. Davies, R. Shikes, C. Sze, Kimberly Leslie, R. Mcduffie, R. Romero, R. Gibbs
Histologic Inflammation In The Maternal And Fetal Compartments In A Rabbit Model Of Acute Intra-Amniotic Infection., J. Davies, R. Shikes, C. Sze, Kimberly Leslie, R. Mcduffie, R. Romero, R. Gibbs
Kimberly K. Leslie
OBJECTIVE: This study was undertaken to determine the course of acute inflammation in the maternal and fetal compartments during experimentally induced ascending intra-amniotic infection. STUDY DESIGN: Forty pregnant rabbits at 70% gestation were inoculated endocervically with 10(5) colony-forming units of Escherichia coli. Does were killed at 0, 4, 8, 16, 24, and 30 hours after inoculation. At necropsy, blood, peritoneal fluid, amniotic fluid, and uterine tissue were cultured. Fetal brain, lung, heart, gut, and kidney were collected for histologic examination. Necrosis, infiltrates, congestion, and edema were each assessed semiquantitatively, and mean composite histologic-inflammation scores were compared with analysis of variance. …
The Role Of Oestrogen In Follicular Development., B. Hurst, Kimberly Leslie
The Role Of Oestrogen In Follicular Development., B. Hurst, Kimberly Leslie
Kimberly K. Leslie
Most of our knowledge of ovarian physiology is based upon studies that have demonstrated functional oestrogen receptors in the ovaries of lower animal species. The presence of oestrogen receptors in primate granulosa cells has been questioned by some investigators. However, we have found oestrogen receptor messenger RNA in human granulosa cells by reverse transcriptase-PCR assay. Furthermore, using immortalized granulosa cell lines transfected with a plasmid containing an oestrogen response element, a functional oestrogen receptor was confirmed. These experiments strongly support the hypothesis that human granulosa cells express biologically active oestrogen receptor.
A Randomized Controlled Trial Of Interleukin-1 Receptor Antagonist In A Rabbit Model Of Ascending Infection In Pregnancy., R. Mcduffie, J. Davies, Kimberly Leslie, S. Lee, M. Sherman, R. Gibbs
A Randomized Controlled Trial Of Interleukin-1 Receptor Antagonist In A Rabbit Model Of Ascending Infection In Pregnancy., R. Mcduffie, J. Davies, Kimberly Leslie, S. Lee, M. Sherman, R. Gibbs
Kimberly K. Leslie
OBJECTIVE: To determine whether treatment with interleukin-1 receptor antagonist (IL1-ra) would affect amniotic fluid concentrations of tumor necrosis factor alpha (TNF-alpha) and prostaglandins or clinical or microbiological outcomes in a model of ascending bacterial infection in pregnancy. METHODS: Timed pregnant New Zealand white rabbits at 70% of gestation underwent endoscopic inoculation of the cervices with 10(6) - 10(7) cfu Escherichia coli. Animals were randomly assigned in a blinded manner to a 5-h intravenous infusion of human IL1-ra (10 mg/kg) or placebo beginning 1-2 h after inoculation. Blood was drawn from the does for assay of serum IL1-ra concentration before inoculation, …
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
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
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
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
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
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
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
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 …