Wagner, J. A membrane-permeable cAMP analog mimicked the effect of PGE1, whereas intracellular application of a cAMP antagonist Rp-cAMP blocked the effect of PGE1. Jan 18, 2022 Updated Mar 17, 2022, 5:09pm PDT Years before Theranos founder Elizabeth Holmes was prosecuted for fraud, Dr. Phyllis Gardner saw right through her. The names listed below are alumni who have been searched for on this site from Troy High Schoolin Fullerton, California . Stimulation of T cells by externally applied PGE1 stimulated 125I efflux and activated a slowly developing membrane current. A., McDonald, T. V., Gardner, P. STIMULATION OF CHLORIDE SECRETION BY P-1 PURINOCEPTOR AGONISTS IN CYSTIC-FIBROSIS PHENOTYPE AIRWAY EPITHELIAL-CELL LINE CFPEO-. This difference was independent of atopy. Dr. Phyllis Gardner, MD, Internal Medicine | Stanford, CA - WebMD Commercially available CF carrier screening panels offer a limited panel of mutations, however, making them insufficiently sensitive for certain groups within an ethnically diverse population. Holmes forged ahead anyway. View details for Web of Science ID 000177015400009. View details for Web of Science ID A1991EZ66600057, In both T- and B-lymphocyte activation, antigen receptor or mitogen stimulation results in phosphoinositide turnover, generation of InsP3 and diacylglycerol, and a sustained rise in intracellular Ca2+, from both intracellular Ca2+ stores release and enhanced transmembrane Ca2+ influx. Wagner, J. 2) via calcineurin. The arrayed primer extension array, based on a platform technology for disease detection with multiple applications, is a robust, cost-effective, and easily modifiable assay suitable for CF carrier screening and disease detection. Previous work with excised inside-out patches suggests that inositol 1,4,5-trisphosphate is the activating second messenger of the voltage-insensitive T-cell Ca2+-permeable channel. A., McDonald, T. V., NGHIEM, P. T., Lowe, A. W., Schulman, H., Gruenert, D. C., Stryer, L., Gardner, P. HUMAN-LYMPHOCYTES TRANSCRIBE THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE AND EXHIBIT CF-DEFECTIVE CAMP-REGULATED CHLORIDE CURRENT. First, patch clamp studies have revealed the presence of a nonvoltage-gated, Ca2+ permeable channel, the probability of whose opening increases upon exposure of the T cell to activating ligands. CF is one of the most extensively researched genetic diseases as a target for gene therapy development. View details for Web of Science ID A1991GP26900012. Dr. Phyllis Gardner Despite Holmes' ability to charm older white businessman, assembling an impressive all-male board of directors at Theranos, there was one person who told her what she was. A., Schulman, H., Gardner, P. ACTIVATION OF CHLORIDE CHANNELS IN NORMAL AND CYSTIC-FIBROSIS AIRWAY EPITHELIAL-CELLS BY MULTIFUNCTIONAL CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE. Single channel recordings by the extracellular patch-clamp technique indicated that Bay K 8644 activated an 8-pS, barium-permeable channel that opened as bursts of brief events. In this study, we tested the feasibility of utilizing DBHQ to improve Cl- secretion via the Ca(2+)-dependent pathway, in the cystic fibrosis (CF)-derived pancreatic epithelial cell line CFPAC-1. In human lymphocytes and epithelial tissues, CaM kinase activates a chloride channel via a Ca(2+)-dependent pathway which is preserved in cystic fibrosis. This hemolysin produces pores in membranes as demonstrated by osmotic protection studies using red blood cells and carbohydrate compounds of various molecular weights. Nitric oxide, which is produced by cytokine-activated mononuclear cells, is thought to play an important role in inflammation and immunity. It is widely accepted that clinical testing using surrogate markers including pulmonary function will be useful in assessing clinical efficacy. We show the cDNA structure of two variants of this human CaM kinase, gamma B and gamma C, which are predicted to translate to 518 and 495 amino acids, respectively. View details for Web of Science ID A1993KR82200022. A., Dong, Y. J., Gruenert, D. C., Gardner, P. ACTIVATION OF INTESTINAL CFTR CL- CHANNEL BY HEAT-STABLE ENTEROTOXIN AND GUANYLIN VIA CAMP-DEPENDENT PROTEIN-KINASE. What Stanford professor Dr. Phyllis Gardner thinks about Theranos Dr. Phyllis Gardner, MD is a board certified internist in Stanford, California. A proteinaceous hemolysin secreted by strain 4074 of serotype 1 of Actinobacillus pleuropneumoniae was purified by diafiltration and ion exchange chromatographic techniques. [1] [2] [3] View details for DOI 10.1586/14737159.6.3.375, View details for Web of Science ID 000237916000010. McDonald, T. V., Premack, B. She received her medical degree from Harvard Medical School and has been in practice for more than 20 years. These results suggest that there is no relationship between P-gp and the chloride channel activated by cell swelling. She trained in Internal Medicine at Massachusetts General Hospital, followed by a Chief Residency at Stanford University Hospital. Ligation of the extracellular domains of the T-cell receptor activates receptor-associated tyrosine kinases that can phosphorylate the gamma-isoform of phospholipase C, increasing its catalytic activity. She is survived by daughters Gina & Michelle as well as seven grandchildren, six great-grandchildren, and her last remaining sibling, Larry. A., Nepomuceno, I. Stimulation of T-lymphocytes via either structure results in opening of an identical set of voltage-insensitive plasma membrane Ca2+-permeable channels through the action of a diffusible second messenger. We show here that Ca2+ ionophore activates Cl- currents in cell-attached and whole-cell patch-clamp recordings of Jurkat T lymphocytes, but this activation is not direct. Season 15: "Theranos CEO on Trial"--Phyllis Gardner - CNBC By means of arrayed primer extension technology, we have designed a genotyping microarray with 204 probe sites for CF transmembrane conductance regulator gene mutation detection. These results suggest that PGE1, acting through PKA, activates a Cl- current in Jurkat T cells. In patch-clamp experiments, ADO (1 mM) induced an outwardly-rectified whole-cell Cl- current (baseline, 2.5 +/- 0.8 pA pF-1, + ADO, 78.4 +/- 23.8 pA pF-1; P < 0.02), which was largely inhibited in cells internally perfused with a selective inhibitory peptide of the multifunctional Ca2+/calmodulin-dependent protein kinase, CaMK [273-302] (20 microM), as compared to a control peptide, CaMK [284-302]. However, the absence of voltage-dependent activation, relative conductance sequence for divalent cations (Ca2+ > Ba2+ approximately Sr2+ > Mn2+), and lack of inhibition by nifedipine, D600, diltiazem, delta-conotoxin, or aga-IVa were unlike that of voltage-gated Ca2+ channels. Stanford's Phyllis Gardner Says She Knew Elizabeth Holmes Was A Fraud A total of 183 mutations were identified, including 14 different amino acid-changing novel variants. View details for Web of Science ID A1994PN23700032, View details for PubMedCentralID PMC1510420. Enhanced opening probability appears to be mediated by the second messenger InsP3, implying that InsP3 is responsible for both intracellular Ca2+ stores release and enhanced transmembrane Ca2+ influx. The expression of the three K+ channel subtypes varies with the cell's developmental state and functional class. View details for Web of Science ID A1993KN53300018. To investigate this signal transduction, plasma membrane calcium-permeable channels were characterized in T-lymphocytes by means of whole cell or single channel patch-clamp recordings. Dr. Phyllis Gardner, MD is an Internal Medicine Specialist in Stanford, CA and has over 47 years of experience in the medical field. Characterization of CFTR mutations in the U.S. Hispanic population is vital to early diagnosis, genetic counseling, patient-specific treatment, and the understanding of cystic fibrosis (CF) pathogenesis. We also discuss agents, including deoxyribonuclease (DNase), that directly reduce sputum viscosity. 6. Danny In The Valley: Dr Phyllis Gardner, Stanford professor and Dr. Phyllis Gardner, MD - Internal Medicine Specialist in Stanford, CA Specialties. SCHUMANN, M. A., Gardner, P., Raffin, T. A. Sequence changes were identified in 11.7% and 10% of presbycusis and control alleles, respectively. A luciferase assay quantitated interleukin-2 gene promoter activity in stimulated cells transfected with an interleukin-2 promoter-luciferase gene construct. (1) A77 1726 inhibited Jurkat T-cell proliferation without inhibiting T-cell receptor-mediated signal transduction events, including tyrosine kinase-dependent intracellular Ca2+ mobilization and activation of the interleukin-2 gene promoter; (2) the antiproliferative effects of A77 1726 on Jurkat T cells are primarily due to interruption of de novo pyrimidine nucleotide biosynthesis. Multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) is a mediator of calcium signals in diverse signaling pathways. The site facilitates research and collaboration in academic endeavors. In the series premiere episode of 'The Dropout,' actress Laurie Metcalf essays the role of Gardner. The Sunday Times' tech correspondent brings on Dr Phyllis Gardner, the Standord medical professor who came across Elizabeth Holmes before she started Theranos and then worked behind the scenes to expose her, to talk about her background at Stanford (4:00), and in industry (5:00), meeting a young Elizabeth Holmes (6:55), rejecting her first idea Gardner recently. (ABSTRACT TRUNCATED AT 400 WORDS), View details for Web of Science ID A1990DA09800009. Ca2+ currents induced by receptor stimulation and Ca(2+)-ATPase inhibition were not additive. She and Rupert Brooke had, on her side at least, a passionate relationship. But Cl- flux in cystic fibrosis cells, as in normal cells, can be activated by raising intracellular Ca2+ (refs 5-10). Chao, A. C., deSauvage, F. J., Dong, Y. J., Wagner, J. Dr. Gardner is currently a Professor with tenure at the School of Medicine at Stanford University, where she has held several positions since she began there in 1984, including Senior Associate Dean for Education and Student Affairs. The ability of SK&F 96365 to inhibit IL-2 synthesis and cell proliferation suggests that a new class of related Ca2+ channel blockers can be developed as immunosuppressive agents. It may also serve as an important model for gene therapy of other diseases. Dr. Phyllis Gardner, a Stanford Medical School professor, was skeptical of the Theranos founder Elizabeth Holmes early on, having rejected Holmes' idea for a patch that could deploy. Learn how we are healing patients through science & compassion, Stanford team stimulates neurons to induce particular perceptions in mice's minds, Students from far and near begin medical studies at Stanford. Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis. SIGNAL TRANSDUCTION BY T-CELL RECEPTORS - MOBILIZATION OF CA AND REGULATION OF CA-DEPENDENT EFFECTOR MOLECULES, ANTISENSE OLIGODEOXYNUCLEOTIDES TO THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR INHIBIT CAMP-ACTIVATED BUT NOT CALCIUM-ACTIVATED CHLORIDE CURRENTS. While STa and guanylin bind to the same receptor guanylyl cyclase and raise cell cGMP, the signaling mechanism distal to cGMP remains controversial. Schrijver, I., Kulm, M., Gardner, P. I., Pergament, E. P., Fiddler, M. B. Clinical manifestations include both pancreatic and pulmonary insufficiency. Chao, A. C., Kouyama, K., Heist, E. K., Dong, Y. J., Gardner, P. ACTIVATION OF CFTR CHLORIDE CURRENT BY NITRIC-OXIDE IN HUMAN T-LYMPHOCYTES. Each of the systems, along with future trends in microfabrication manufacturing, limitations and possibilities, are discussed. Is CFTR also required for the calcium-dependent activation of chloride channels? Multifunctional CaM kinase also attenuated interleukin-2 activation by calcineurin plus phorbol ester. Specific attenuation of interleukin-2 transcriptional induction occurs in Jurkat T cells following pretreatment with a Ca2+ ionophore. About Phyllis Gardner, M.D. PHYLLIS STANKO OBITUARY. View details for Web of Science ID 000228736900018. tgAAVCF, an adeno-associated cystic fibrosis transmembrane conductance regulator (CFTR) viral vector/gene construct, was administered to 23 patients in a Phase II, double-blind, randomized, placebo-controlled clinical trial. Phyllis Gardner (6 October 1890 - 16 February 1939) was a writer, artist, and noted breeder of Irish Wolfhounds. Dr. Phyllis Gardner, MD, is an Internal Medicine specialist practicing in Stanford, CA with 47 years of experience. Dong, Y. J., Chao, A. C., Kouyama, K., Hsu, Y. P., BOCIAN, R. C., Moss, R. B., Gardner, P. MOLECULAR STRATEGIES FOR THERAPY OF CYSTIC-FIBROSIS, INHIBITION BY SK-AND-F-96365 OF CA2+ CURRENT, IL-2 PRODUCTION AND ACTIVATION IN T-LYMPHOCYTES. Here we show that STa, guanylin and cGMP each activate intestinal Cl- secretion, and that this is abolished by inhibitors of cAMP-dependent protein kinase (PKA), suggesting that PKA is a major mediator of this effect. Pretreatment of CFPAC-1 cells with up to 50 microM DBHQ for 6 h did not cause any detectable change in cell viability and did not significantly affect the cell proliferation rate. 1. This discrepancy is even more pronounced when such carrier screening panels are used for diagnostic purposes. In the futuristic ideal, these systems would involve the implantation of precisely microfabricated drug delivery systems with nanopores, nanochannels and/or nanoreservoirs fabricated from silicon, coupled with electronic sensing and actuator systems, for the precise, timed and/or targeted delivery of drugs. Gardner was one of the first people to be publicly skeptical of Elizabeth Holmes, the founder of blood testing company Theranos, who was later found guilty of investor fraud. She graduated from Harvard University / School Of Medicine in 1976. Phyllis Gardner is part of Stanford Profiles, official site for faculty, postdocs, students and staff information (Expertise, Bio, Research, Publications, and more). Assessing the biological activity and clinical efficacy of gene therapy is critically important in cystic fibrosis (CF). Over one third of the mutations (27/85) occurred with a relative frequency >1%, which illustrates that the identified mutations are not all rare. Furthermore, the 3'-end of the gene was found in a T cell cDNA library. Microsomal Ca(2+)-ATPase inhibitors such as thapsigargin (THG), cyclopiazonic acid (CPA) and 2,5-di-(tert-butyl)-1,4-hydroquinone (DBHQ) have been shown to inhibit Ca2+ reuptake by the intracellular stores and increase cytosolic free Ca2+ ([Ca2+]i). Cystic fibrosis (CF) is a common genetic disorder characterized by defective epithelial chloride transport and progressive lung disease. Born on July 7, 1950, Phyllis Gardner is an American biologist who is known for being one of the first people to oppose and criticize the ideas of Elizabeth Holmes. Because GSK-3 responds to signals initiated by Wnt and other ligands, NF-AT family members could be effectors of these pathways. . The predominant effect of Bay K 8644 on these channels was to increase the probability of channel reopening, apparently without a major effect on mean channel open-time. Dr. Gardner has spent more than 35 years in academia, medicine and industry. Nghiem, P., SAATI, S. M., Martens, C. L., Gardner, P., Schulman, H. FLASH-PHOTOLYSIS OF CAGED INOSITOL 1,4,5-TRISPHOSPHATE ACTIVATES PLASMA-MEMBRANE CALCIUM CURRENT IN HUMAN T-CELLS. View details for Web of Science ID A1988Q219900001, Department: Medicine - Med/Clinical Pharmacology, Genetic Analysis of Presbycusis by Arrayed Primer Extension. The data demonstrate a modulation of T-lymphocyte K+ channels by substance P and substantiate a possible role for GTP-binding proteins in this modulation. Dose-dependent changes in TEPD responses to pharmacologic intervention were observed following treatments. She's a professor of medicine at Stanford and a former partner in a health care venture capital firm. Several nonlinear internal feedback controls may contribute to the periodic nature of the Ca2+ signal: PKC-mediated phosphorylation of the CD3 gamma subunit, which is a feedback inhibitor of TCR/CD3 function; amplification of Ca2+ release from endoplasmic reticulum by a highly cooperative step in the opening of Ca2+ channels by InsP3, and Ca2+-dependent feedback enhancement of PLC function; autoregulatory negative feedback on Ca2+ influx by Ca2+, both by a direct effect on the plasma membrane Ca2+ channel and by induction of membrane hyperpolarization secondary to Ca2+-activated K+ efflux. Gardner recently opened up about her distrust and dislike . She attended Stanford University, where she first came up with the idea for her company, Theranos. View details for Web of Science ID A1991GF80400001. View details for Web of Science ID 000260722000005. Calcineurin dephosphorylates conserved serine residues in the amino terminus of NF-AT, resulting in nuclear import. A prolonged (at least 2-4 hr) elevation of [Ca2+]i accompanies early T cell activation by TCR/CD3-specific ligands. Secretion of interferon-gamma, IL-2, and IL-4 was comparable in CF and control TCC after both forms of activation, while IL-5 was reduced in CF TCC following anti-CD3/phorbol myristate acetate (PMA) but not after Con A. While the function of nitric oxide as a direct cytotoxic effector molecule is well established, its function as a transducer molecule in immune cells is not. A chloride ion transport defect has been described in human CF-derived lymphocytes; however, it has not been possible to detect CFTR mRNA in lymphocytes.
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