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Full-Text Articles in Medicine and Health Sciences
Expression And Localization Of Nrf2/Keap1 Signalling Pathway Genes In Mouse Preimplantation Embryos Exposed To Free Fatty Acids., Grace Dionne, Michele D. Calder, Dean H Betts, Basim Abu Rafea, Andrew J Watson
Expression And Localization Of Nrf2/Keap1 Signalling Pathway Genes In Mouse Preimplantation Embryos Exposed To Free Fatty Acids., Grace Dionne, Michele D. Calder, Dean H Betts, Basim Abu Rafea, Andrew J Watson
Obstetrics & Gynaecology Publications
Obese women experience greater incidence of infertility, with reproductive tracts exposing preimplantation embryos to elevated free fatty acids (FFA) such as palmitic acid (PA) and oleic acid (OA). PA treatment impairs mouse preimplantation development in vitro, while OA co-treatment rescues blastocyst development of PA treated embryos. In the present study, we investigated the effects of PA and OA treatment on NRF2/Keap1 localization, and relative antioxidant enzyme (Glutathione peroxidase; Gpx1, Catalase; Cat, Superoxide dismutase; Sod1 and γ-Glutamylcysteine ligase catalytic unit; Gclc) mRNA levels, during in vitro mouse preimplantation embryo development. Female mice were superovulated, mated, and embryos cultured in the presence …
The Effects Of Total Body Proton Irradiation On Mouse Myometrium, Lillith Bulawa
The Effects Of Total Body Proton Irradiation On Mouse Myometrium, Lillith Bulawa
Undergraduate Honors Theses
The boundaries of human space exploration continue to expand with new technology and discoveries making it even more important to investigate the effects of space on biological systems. Although humans have explored space in small increments, reproductive studies must be conducted to determine if stable short- or long-term residences for humans can exist in space. This study explored the effects of whole-body proton radiation on uterine smooth muscle known as the myometrium. Two types of mice utilized in this study were C57BL/6 and B6.129S6Cybbtm1Din/J NOX2 knockout mice. C57BL/6 mice are standard laboratory mice that were used to represent the wildtype …
Simulated Diabetic Ketoacidosis Therapy In Vitro Elicits Brain Cell Swelling Via Sodium-Hydrogen Exchange And Anion Transport., Keeley L Rose, Andrew J Watson, Thomas A Drysdale, Gediminas Cepinskas, Melissa Chan, C Anthony Rupar, Douglas D Fraser
Simulated Diabetic Ketoacidosis Therapy In Vitro Elicits Brain Cell Swelling Via Sodium-Hydrogen Exchange And Anion Transport., Keeley L Rose, Andrew J Watson, Thomas A Drysdale, Gediminas Cepinskas, Melissa Chan, C Anthony Rupar, Douglas D Fraser
Obstetrics & Gynaecology Publications
A common complication of type 1 diabetes mellitus is diabetic ketoacidosis (DKA), a state of severe insulin deficiency. A potentially harmful consequence of DKA therapy in children is cerebral edema (DKA-CE); however, the mechanisms of therapy-induced DKA-CE are unknown. Our aims were to identify the DKA treatment factors and membrane mechanisms that might contribute specifically to brain cell swelling. To this end, DKA was induced in juvenile mice with the administration of the pancreatic toxins streptozocin and alloxan. Brain slices were prepared and exposed to DKA-like conditions in vitro. Cell volume changes were imaged in response to simulated DKA therapy. …
Implantation Failure In Female Kiss1-/- Mice Is Independent Of Their Hypogonadic State And Can Be Partially Rescued By Leukemia Inhibitory Factor., Michele Calder, Yee-Ming Chan, Renju Raj, Macarena Pampillo, Adrienne Elbert, Michelle Noonan, Carolina Gillio-Meina, Claudia Caligioni, Nathalie G Bérubé, Moshmi Bhattacharya, Andrew J Watson, Stephanie B Seminara, Andy V Babwah
Implantation Failure In Female Kiss1-/- Mice Is Independent Of Their Hypogonadic State And Can Be Partially Rescued By Leukemia Inhibitory Factor., Michele Calder, Yee-Ming Chan, Renju Raj, Macarena Pampillo, Adrienne Elbert, Michelle Noonan, Carolina Gillio-Meina, Claudia Caligioni, Nathalie G Bérubé, Moshmi Bhattacharya, Andrew J Watson, Stephanie B Seminara, Andy V Babwah
Obstetrics & Gynaecology Publications
The hypothalamic kisspeptin signaling system is a major positive regulator of the reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in infertility, a condition generally attributed to its hypogonadotropic hypogonadism. We demonstrate that in Kiss1(-/-) female mice, acute replacement of gonadotropins and estradiol restores ovulation, mating, and fertilization; however, these mice are still unable to achieve pregnancy because embryos fail to implant. Progesterone treatment did not overcome this defect. Kiss1(+/-) embryos transferred to a wild-type female mouse can successfully implant, demonstrating the defect is due to maternal factors. Kisspeptin and its receptor are expressed in the mouse …
Stress-Inducible Phosphoprotein 1 Has Unique Cochaperone Activity During Development And Regulates Cellular Response To Ischemia Via The Prion Protein., Flavio H Beraldo, Iaci N Soares, Daniela F Goncalves, Jue Fan, Anu A Thomas, Tiago G Santos, Amro H Mohammad, Martin Roffé, Michele D Calder, Simona Nikolova, Glaucia N Hajj, Andre L Guimaraes, Andre R Massensini, Ian Welch, Dean H Betts, Robert Gros, Maria Drangova, Andrew J Watson, Robert Bartha, Vania F Prado, Vilma R Martins, Marco A M Prado
Stress-Inducible Phosphoprotein 1 Has Unique Cochaperone Activity During Development And Regulates Cellular Response To Ischemia Via The Prion Protein., Flavio H Beraldo, Iaci N Soares, Daniela F Goncalves, Jue Fan, Anu A Thomas, Tiago G Santos, Amro H Mohammad, Martin Roffé, Michele D Calder, Simona Nikolova, Glaucia N Hajj, Andre L Guimaraes, Andre R Massensini, Ian Welch, Dean H Betts, Robert Gros, Maria Drangova, Andrew J Watson, Robert Bartha, Vania F Prado, Vilma R Martins, Marco A M Prado
Obstetrics & Gynaecology Publications
Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the …
Developing An Artificial Fallopian Tube: Successful In Vitro Trials In Mice., Stephen Hunter, J. Neeld, J. Scott, D. Olsen, R. Urry, T. Cichocki
Developing An Artificial Fallopian Tube: Successful In Vitro Trials In Mice., Stephen Hunter, J. Neeld, J. Scott, D. Olsen, R. Urry, T. Cichocki
Stephen K. Hunter
This report describes the design and testing of an artificial fallopian tube for the treatment of tubal infertility. Within the device, mouse eggs incubated with sperm were fertilized and a microinfusion pump was used to transport the fertilized ova through the tube. Normal offspring resulted from transfer of the developing embryos into pseudopregnant recipients. These results provide encouraging evidence that an artificial fallopian tube warrants further investigation as a potential alternative to in vitro fertilization.
The Gamete And Embryo Compatibility Of Various Synthetic Polymers., Stephen Hunter, J. Scott, D. Hull, R. Urry
The Gamete And Embryo Compatibility Of Various Synthetic Polymers., Stephen Hunter, J. Scott, D. Hull, R. Urry
Stephen K. Hunter
Several popular and well-characterized polymeric materials were evaluated for their biocompatibility toward the cells unique to reproduction. To accomplish these studies, several in vitro tests were developed that evaluated biocompatibility between the polymers and spermatozoa, ova, and embryos. The data indicated significant differences between the materials with respect to their biocompatibility toward sperm motility, the sperm's ability to penetrate zona-free hamster eggs, and the ability of two-cell mouse embryos to divide. Polytetrafluoroethylene (PTFE-Teflon; PTFE, Chemplast Inc., Wayne, NJ), polyethylene glycol (PEG), and polyhydroxyethyl methacrylate (PHEMA) appear to be the most inert of the materials studied. Polyvinyl chloride (PVC; Tygon-Norton, Akron, …
Surface Modification Of Polyurethane To Promote Long-Term Patency Of Peritoneal Access Devices., Stephen Hunter, D. Gregonis, D. Coleman, B. Hanover, R. Stephen, S. Jacobsen
Surface Modification Of Polyurethane To Promote Long-Term Patency Of Peritoneal Access Devices., Stephen Hunter, D. Gregonis, D. Coleman, B. Hanover, R. Stephen, S. Jacobsen
Stephen K. Hunter
No abstract provided.
Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter
Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter
Stephen K. Hunter
OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry. RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …
Gene Modification Via "Plug And Socket" Gene Targeting., J. Lewis, Baoli Yang, P. Detloff, O. Smithies
Gene Modification Via "Plug And Socket" Gene Targeting., J. Lewis, Baoli Yang, P. Detloff, O. Smithies
Baoli Yang
No abstract provided.
A Common Human Beta Globin Splicing Mutation Modeled In Mice., J. Lewis, Baoli Yang, R. Kim, H. Sierakowska, R. Kole, O. Smithies, N. Maeda
A Common Human Beta Globin Splicing Mutation Modeled In Mice., J. Lewis, Baoli Yang, R. Kim, H. Sierakowska, R. Kole, O. Smithies, N. Maeda
Baoli Yang
The betaIVS-2-654 C-->T mutation accounts for approximately 20% of beta thalassemia mutations in southern China; it causes aberrant RNA splicing and leads to beta0 thalassemia. To provide an animal model for testing therapies for correcting splicing defects, we have used the "plug and socket" method of gene targeting in murine embryonic stem cells to replace the two (cis) murine adult beta globin genes with a single copy of the human betaIVS-2-654 gene. No homozygous mice survive postnatally. Heterozygous mice carrying this mutant gene produce reduced amounts of the mouse beta globin chains and no human beta globin, and have …
Fetal Hemorrhage And Platelet Dysfunction In Slp-76-Deficient Mice., J. Clements, J. Lee, B. Gross, Baoli Yang, J. Olson, A. Sandra, S. Watson, S. Lentz, G. Koretzky
Fetal Hemorrhage And Platelet Dysfunction In Slp-76-Deficient Mice., J. Clements, J. Lee, B. Gross, Baoli Yang, J. Olson, A. Sandra, S. Watson, S. Lentz, G. Koretzky
Baoli Yang
The adapter protein SLP-76 is expressed in T lymphocytes and hematopoietic cells of the myeloid lineage, and is known to be a substrate of the protein tyrosine kinases that are activated after ligation of the T-cell antigen receptor. Transient overexpression of SLP-76 in a T-cell line potentiates transcriptional activation after T-cell receptor ligation, while loss of SLP-76 expression abrogates several T-cell receptor-dependent signaling pathways. Mutant mice that lack SLP-76 manifest a severe block at an early stage of thymocyte development, implicating SLP-76 in signaling events that promote thymocyte maturation. While it is clear that SLP-76 plays a key role in …
Syntaxin 4 Heterozygous Knockout Mice Develop Muscle Insulin Resistance., C. Yang, K. Coker, J. Kim, S. Mora, D. Thurmond, A. Davis, Baoli Yang, R. Williamson, G. Shulman, J. Pessin
Syntaxin 4 Heterozygous Knockout Mice Develop Muscle Insulin Resistance., C. Yang, K. Coker, J. Kim, S. Mora, D. Thurmond, A. Davis, Baoli Yang, R. Williamson, G. Shulman, J. Pessin
Baoli Yang
To investigate the physiological function of syntaxin 4 in the regulation of GLUT4 vesicle trafficking, we used homologous recombination to generate syntaxin 4-knockout mice. Homozygotic disruption of the syntaxin 4 gene results in early embryonic lethality, whereas heterozygous knockout mice, Syn4(+/-), had normal viability with no significant impairment in growth, development, or reproduction. However, the Syn4(+/-) mice manifested impaired glucose tolerance with a 50% reduction in whole-body glucose uptake. This defect was attributed to a 50% reduction in skeletal muscle glucose transport determined by 2-deoxyglucose uptake during hyperinsulinemic-euglycemic clamp procedures. In parallel, insulin-stimulated GLUT4 translocation in skeletal muscle was also …
The Ubiquitin Ligase Adaptor Ndfip1 Regulates T Cell-Mediated Gastrointestinal Inflammation And Inflammatory Bowel Disease Susceptibility., H. Ramon, C. Riling, J. Bradfield, Baoli Yang, H. Hakonarson, P. Oliver
The Ubiquitin Ligase Adaptor Ndfip1 Regulates T Cell-Mediated Gastrointestinal Inflammation And Inflammatory Bowel Disease Susceptibility., H. Ramon, C. Riling, J. Bradfield, Baoli Yang, H. Hakonarson, P. Oliver
Baoli Yang
Nedd4 family interacting protein 1 (Ndfip1) is an adaptor protein that regulates Itch, an E3 ubiquitin ligase that ubiquitylates JunB, thereby preventing interleukin (IL)-4 and IL-5 production. Mice lacking Ndfip1 or Itch develop T helper type 2 (T(H)2)-mediated inflammation in the skin and lungs and die prematurely. In this study we show that Ndfip1-/- mice also develop inflammation in the gastrointestinal tract. Inflammation is characterized by infiltration of eosinophils and T cells and is accompanied by a failure to gain weight. T cells are both necessary and sufficient for eosinophil recruitment and inflammation. This is because Ndfip1-/- T cells become …
Disruption Of The Beta Subunit Of The Epithelial Na+ Channel In Mice: Hyperkalemia And Neonatal Death Associated With A Pseudohypoaldosteronism Phenotype., F. Mcdonald, Baoli Yang, R. Hrstka, H. Drummond, D. Tarr, P. Mccray, J. Stokes, M. Welsh, R. Williamson
Disruption Of The Beta Subunit Of The Epithelial Na+ Channel In Mice: Hyperkalemia And Neonatal Death Associated With A Pseudohypoaldosteronism Phenotype., F. Mcdonald, Baoli Yang, R. Hrstka, H. Drummond, D. Tarr, P. Mccray, J. Stokes, M. Welsh, R. Williamson
Baoli Yang
The epithelial Na+ channel (ENaC) is composed of three homologous subunits: alpha, beta and gamma. We used gene targeting to disrupt the beta subunit gene of ENaC in mice. The betaENaC-deficient mice showed normal prenatal development but died within 2 days after birth, most likely of hyperkalemia. In the -/- mice, we found an increased urine Na+ concentration despite hyponatremia and a decreased urine K+ concentration despite hyperkalemia. Moreover, serum aldosterone levels were increased. In contrast to alphaENaC-deficient mice, which die because of defective lung liquid clearance, neonatal betaENaC deficient mice did not die of respiratory failure and showed only …
A Mouse Model For Beta 0-Thalassemia., Baoli Yang, S. Kirby, J. Lewis, P. Detloff, N. Maeda, O. Smithies
A Mouse Model For Beta 0-Thalassemia., Baoli Yang, S. Kirby, J. Lewis, P. Detloff, N. Maeda, O. Smithies
Baoli Yang
We have used a "plug and socket" targeting technique to generate a mouse model of beta 0-thalassemia in which both the b1 and b2 adult globin genes have been deleted. Mice homozygous for this deletion (Hbbth-3/Hbbth-3) die perinatally, similar to the most severe form of Cooley anemia in humans. Mice heterozygous for the deletion appear normal, but their hematologic indices show characteristics typical of severe thalassemia, including dramatically decreased hematocrit, hemoglobin, red blood cell counts, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration, as well as dramatically increased reticulocyte counts, serum bilirubin concentrations, and red cell distribution …
Appropriate Tissue- And Cell-Specific Expression Of A Single Copy Human Angiotensinogen Transgene Specifically Targeted Upstream Of The Hprt Locus By Homologous Recombination., B. Cvetkovic, Baoli Yang, R. Williamson, C. Sigmund
Appropriate Tissue- And Cell-Specific Expression Of A Single Copy Human Angiotensinogen Transgene Specifically Targeted Upstream Of The Hprt Locus By Homologous Recombination., B. Cvetkovic, Baoli Yang, R. Williamson, C. Sigmund
Baoli Yang
Development of experimental models by genetic manipulation in mice has proven to be very useful in determining the significance of particular genes in the development of or susceptibility to hypertension. Advances in molecular genetics, transgenic mouse technology, and physiological measurements in mice provided an opportunity to go a step further and develop models to analyze the physiological significance of specific gene variants potentially causing hypertension. In this report, we describe the development of a human angiotensinogen transgenic mouse model generated by targeting the human angiotensinogen gene upstream of the mouse HPRT locus by homologous recombination. The main benefit of this …
Requirement For The Leukocyte-Specific Adapter Protein Slp-76 For Normal T Cell Development., J. Clements, Baoli Yang, S. Ross-Barta, S. Eliason, R. Hrstka, R. Williamson, G. Koretzky
Requirement For The Leukocyte-Specific Adapter Protein Slp-76 For Normal T Cell Development., J. Clements, Baoli Yang, S. Ross-Barta, S. Eliason, R. Hrstka, R. Williamson, G. Koretzky
Baoli Yang
The leukocyte-specific adapter molecule SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kilodaltons) is rapidly phosphorylated on tyrosine residues after receptor ligation in several hematopoietically derived cell types. Mice made deficient for SLP-76 expression contained no peripheral T cells as a result of an early block in thymopoiesis. Macrophage and natural killer cell compartments were intact in SLP-76-deficient mice, despite SLP-76 expression in these lineages in wild-type mice. Thus, the SLP-76 adapter protein is required for normal thymocyte development and plays a crucial role in translating signals mediated by pre-T cell receptors into distal biochemical events.
The Mammalian Sodium Channel Bnc1 Is Required For Normal Touch Sensation., M. Price, G. Lewin, S. Mcilwrath, C. Cheng, J. Xie, P. Heppenstall, C. Stucky, A. Mannsfeldt, T. Brennan, H. Drummond, J Qiao, C. Benson, D Tarr, R Hrstka, Baoli Yang, R. Williamson, M. Welsh
The Mammalian Sodium Channel Bnc1 Is Required For Normal Touch Sensation., M. Price, G. Lewin, S. Mcilwrath, C. Cheng, J. Xie, P. Heppenstall, C. Stucky, A. Mannsfeldt, T. Brennan, H. Drummond, J Qiao, C. Benson, D Tarr, R Hrstka, Baoli Yang, R. Williamson, M. Welsh
Baoli Yang
Of the vertebrate senses, touch is the least understood at the molecular level The ion channels that form the core of the mechanosensory complex and confer touch sensitivity remain unknown. However, the similarity of the brain sodium channel 1 (BNC1) to nematode proteins involved in mechanotransduction indicated that it might be a part of such a mechanosensor. Here we show that disrupting the mouse BNC1 gene markedly reduces the sensitivity of a specific component of mechanosensation: low-threshold rapidly adapting mechanoreceptors. In rodent hairy skin these mechanoreceptors are excited by hair movement. Consistent with this function, we found BNC1 in the …
Regulation Of Terminal Deoxynucleotidyl Transferase Gene Expression In Mice And Men., M. Coleman, Baoli Yang, D. Sorscher
Regulation Of Terminal Deoxynucleotidyl Transferase Gene Expression In Mice And Men., M. Coleman, Baoli Yang, D. Sorscher
Baoli Yang
A nontemplate directed DNA polymerase, terminal deoxynucleotidyl transferase (terminal transferase) is expressed in a tissue-specific and development stage-specific manner. Its enzymatic properties and tissue localization have implicated the protein in development of normal immune function. Significant progress has been made in understanding the enzymology and important domains of this protein. More recently, studies have focused on regulation of the gene that codes for the protein in mice and humans. The murine gene has yielded to these studies more readily than the human gene. A murine basal promoter element has been identified along with several trans-acting protein factors that may regulate …
Loss Of Mll Phd Finger 3 Is Necessary For Mll-Enl-Induced Hematopoietic Stem Cell Immortalization, J. Chen, Donna Santillan, M. Koonce, W. Wei, R. Luo, M. Thirman, N. Zeleznik-Le, M. Diaz
Loss Of Mll Phd Finger 3 Is Necessary For Mll-Enl-Induced Hematopoietic Stem Cell Immortalization, J. Chen, Donna Santillan, M. Koonce, W. Wei, R. Luo, M. Thirman, N. Zeleznik-Le, M. Diaz
Donna A. Santillan
Reciprocal chromosomal translocations at the MLL gene locus result in expression of novel fusion proteins, such as MLL-ENL, associated with leukemia. The three PHD finger cassette, one of the highly conserved domains in MLL, is absent in all fusion proteins. This domain has been shown to interact with Cyp33, a cyclophilin which enhances the recruitment of histone deacetylases (HDAC) to the MLL repression domain and mediates HOX gene repression. Insertion of the third PHD finger of MLL into MLL-ENL allows the recruitment of Cyp33 and, subsequently, HDAC1 to the fusion protein. Furthermore, expression of the fusion protein with the PHD …
Bromodomain And Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype, Donna Santillan, C. Theisler, A. Ryan, R. Popovic, T. Stuart, M. Zhou, S. Alkan, N. Zeleznik-Le
Bromodomain And Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype, Donna Santillan, C. Theisler, A. Ryan, R. Popovic, T. Stuart, M. Zhou, S. Alkan, N. Zeleznik-Le
Donna A. Santillan
A critical unanswered question about mixed lineage leukemia (MLL) is how specific MLL fusion partners control leukemia phenotype. The MLL-cyclic AMP-responsive element binding protein-binding protein (CBP) fusion requires both the CBP bromodomain and histone acetyltransferase (HAT) domain for transformation and causes acute myelogenous leukemia (AML), often preceded by a myelodysplastic phase. We did domain-swapping experiments to define whether unique specificities of these CBP domains drive this specific MLL phenotype. Within MLL-CBP, we replaced the CBP bromodomain or HAT domain with P300/CBP-associated factor (P/CAF) or TAF(II)250 bromodomains or the P/CAF or GCN5 HAT domains. HAT, but not bromodomain, substitutions conferred enhanced …
Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter
Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter
Donna A. Santillan
OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry. RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …
Efficacy Of Polymeric Encapsulated C5a Peptidase-Based Group B Streptococcus Vaccines In A Murine Model, Donna Santillan, K. Rai, Mark Santillan, Y. Krishnamachari, A. Salem, S. Hunter
Efficacy Of Polymeric Encapsulated C5a Peptidase-Based Group B Streptococcus Vaccines In A Murine Model, Donna Santillan, K. Rai, Mark Santillan, Y. Krishnamachari, A. Salem, S. Hunter
Donna A. Santillan
OBJECTIVE: The purpose was to examine in mice the efficacy of various polymeric-encapsulated C5a peptidase vaccine formulations in eliciting a long-term immune response and preventing group B streptococcus (GBS) infection. STUDY DESIGN: C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-coglycolide) (PLGA). Female ICR mice were immunized with 0, 10, or 30 mug of encapsulated C5a peptidase within 2 different formulations of PLGA polymers. Booster doses were given at weeks 4 and 8. Antibody responses were measured by enzyme-linked immunosorbent assay at weeks 4, 8, 11, and 40. Vaginal challenges with GBS types 1a, III, and V were performed at …
Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter
Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter
Mark K. Santillan
OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry. RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …
Gene Transfer Efficiency During Gestation And The Influence Of Co-Transfer Of Non-Manipulated Embryos On Production Of Transgenic Mice, R. Canseco, Amy Sparks, R. Page, C. Russell, J. Johnson, W. Velander, R. Pearson, W. Drohan, F. Gwazdauskas
Gene Transfer Efficiency During Gestation And The Influence Of Co-Transfer Of Non-Manipulated Embryos On Production Of Transgenic Mice, R. Canseco, Amy Sparks, R. Page, C. Russell, J. Johnson, W. Velander, R. Pearson, W. Drohan, F. Gwazdauskas
Amy E.T. Sparks
Litter size of DNA microinjected zygotes is lower than for non-manipulated zygotes. The rate of embryonic and fetal survival in early, mid and late gestation was determined to assess whether DNA integration was responsible for embryonic losses. Also, the effect of including non-microinjected embryos with injected embryos on pregnancy rate and transgenic pup production was determined. In Experiment 1, one-cell embryos from immature CD-1 mice were microinjected with a whey acidic protein promoter-human protein C gene construct. One hour after microinjection embryos were transferred to pseudopregnant recipients (45 transfers of 30 embryos each). Fifteen recipients were sacrificed on day 4, …
Encapsulated Beta-Islet Cells As A Bioartificial Pancreas To Treat Insulin-Dependent Diabetes During Pregnancy, Stephen Hunter, Y. Wang, C. Weiner, Jennifer Niebyl
Encapsulated Beta-Islet Cells As A Bioartificial Pancreas To Treat Insulin-Dependent Diabetes During Pregnancy, Stephen Hunter, Y. Wang, C. Weiner, Jennifer Niebyl
Jennifer R Niebyl
OBJECTIVE: Our purpose was to determine the effectiveness of the bioartificial pancreas technique in correcting (1) maternal carbohydrate metabolism and (2) fetal malformation rates in a pregnant diabetic animal model. STUDY DESIGN: Insulin secretion from encapsulated rat islets cultured in the presence of homologous rat prolactin was determined and compared with that of controls. Streptozotocin-induced diabetic Balb/c mice were then transplanted with rat islet cells encapsulated within alginate microbeads and were then bred. Blood glucose determinations were made after transplantation and throughout gestation. Pups were delivered by cesarean section on day 19 of gestation. Outcome parameters from the transplanted study …
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
Xiangbing Meng
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 …
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
Xiangbing Meng
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 …
Biodegradable Microspheres Containing Group B Streptococcus Vaccine: Immune Response In Mice, Stephen Hunter, M. Andracki, A. Krieg
Biodegradable Microspheres Containing Group B Streptococcus Vaccine: Immune Response In Mice, Stephen Hunter, M. Andracki, A. Krieg
Stephen K. Hunter
OBJECTIVE: This study seeks to show the feasibility of producing a group B Streptococcus (GBS) vaccine, which is capable of producing both a local IgA immune response at the mucosal surface where GBS is colonized and a humoral IgG response, which is capable of transplacental passive immunization. STUDY DESIGN: Inactivated GBS antigen was microencapsulated in poly (D, L-lactic-co-glycolic acid) (PLG) with a water-in-oil-in-water double emulsion technique. Immunostimulatory synthetic oligodeoxynucleotides containing cytidine-phosphate-guanosine (CpG) motifs were coencapsulated as a potent adjuvant. The ICR strain of mouse was used in these studies. Female mice with normal immune systems were immunized with the PLG …