The mutation spectrum in Hispanics, however, remains poorly defined. The known potent A2 adenosine receptor (A2AR) agonist, 5'-(N-cyclopropyl) carboxamidoadenosine (CPCA, 2 microM) but not the A1 adenosine receptor agonist, N6-phenyl adenosine (N6-phenyl ADO, 10 microM) markedly increased 125I efflux rate (baseline, 5.9 +/- 2.0% min-1, + CPCA, 10.9 +/- 0.6% min-1; P < 0.01). T-cell receptor signalling activates multifunctional CaM kinase. The maximal effects were seen at concentrations of 25-50 microM. Dr. Gardner brings to the CohBar Board over 35 years of experience in academia, medicine, pharmacology, drug delivery systems, and biotechnology investing and governance, and has received numerous national awards and honors. NFAT mediated gene transcription; modulations by kinases and phosphatases. Ion channels, and ion fluxes in general, appear to regulate a wide variety of processes important to lymphocyte function in normal and disease states. 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. Dr. Phyllis Gardner, MD is an Internal Medicine Specialist in Stanford, CA and has over 47 years of experience in the medical field. 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. We are interested in the general process of signal transduction, focusing on the role that ion channels play in this process. She is currently licensed to practice medicine in California. You may use our global navigation in the heading bar or return to our home page using the buttons below. Season 15: "Theranos CEO on Trial"--Phyllis Gardner American Greed reveals fresh details about one of the most infamous alleged corporate fraud cases of the 21st century - Theranos, now back in. Deafness and hearing impairment have a genetic cause in at least half the cases. SK&F 96365 has no effect on Ca2+ stores release or K+ channels. View details for Web of Science ID A1989AK17900033. About Phyllis Gardner, M.D. View details for Web of Science ID A1994NA28800008, View details for Web of Science ID A1994BB86U00010. While STa and guanylin bind to the same receptor guanylyl cyclase and raise cell cGMP, the signaling mechanism distal to cGMP remains controversial. This provider currently accepts 5 insurance plans. Lifetime resident of Fullerton, passed away on 11/18/21 in her home. Bath application of 1000 units/ml recombinant human TNF alpha (rhTNF alpha) induced a rise in cytosolic free Ca2+ in 75% of fluo-3-loaded cells, 25% of which displayed irregular patterns of oscillation. View details for DOI 10.1542/peds.2005-2519, View details for Web of Science ID 000240959100016. The P1 agonists tested (at 0.01 and 0.1 mM) revealed a rank order of potency of 5'-N-ethylcarboxamine adenosine (NECA) > 2-chloro-adenosine (2-Cl-ADO) > R-phenylisopropyl adenosine (R-PIA). These channels in normal cells are activated by cyclic AMP-dependent protein kinase and protein kinase C. In cystic fibrosis these kinases fail to activate otherwise normal Cl- channels. The voltage-activated K+ channel is postulated to have a role in mitogenesis, based on studies that demonstrate an increase in K+ channel amplitude in the 24-48 hr following mitogen stimulation, and on studies that demonstrate that K+ channel blockers inhibit mitogenesis in a dose-dependent manner with the same potency sequence for ion channel block. About Phyllis Gardner, M.D. It is unclear whether or not this type of Ca2+ channel is present in straight B-cell lines. B-lymphoblasts from CF-affected humans demonstrated defective Cl- conductance regulation by cAMP but preserved regulation by calcium-mediated and volume regulation mechanisms. Traditional therapeutic modalities address these problems with pancreatic enzyme replacement, vitamins and nutritional supplementation, antibiotics, and respiratory therapy. Dr. Phyllis Gardner, MD, is an Internal Medicine specialist practicing in Stanford, CA with 47 years of experience. A., Messner, A. H., Moran, M. L., DAIFUKU, R., Kouyama, K., Desch, J. K., Manley, S., Norbash, A. M., Conrad, C. K., Friborg, S., Reynolds, T., Guggino, W. B., Moss, R. B., Carter, B. J., Wine, J. J., Flotte, T. R., Gardner, P. Maxillary sinusitis as a surrogate model for CF gene therapy clinical trials in patients with antrostomies. Future molecular diagnostic assays are expected to offer a greater variety of gene-specific tests, as well as combined mutation panels, which will aid in the management of the impressive genetic heterogeneity observed in hereditary hearing loss, especially in individuals with nonsyndromic forms. Neither the primary efficacy endpoint, defined as the rate of relapse of clinically defined, endoscopically diagnosed recurrent sinusitis, nor several secondary endpoints (sinus transepithelial potential difference [TEPD], histopathology, sinus fluid interleukin [IL]-8 measurements) achieved statistical significance when comparing treated to control sinuses within patients. Phyllis Gardner, Stanford University professor of medicine and health care venture capital firm partner, on her early suspicions about disgraced Theranos founder Elizabeth Holmes, whom she . 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. Patch clamp studies in T and B cells have revealed the presence of several types of ion channels that apparently contribute to the ion fluxes and to the membrane potential changes associated with lymphocyte activation. Gardner is played by actress Laurie Metcalf in the series premiere episode of 'The Dropout.' These agents induce Cl- secretion only in cells expressing the wild-type CFTR, indicating that this molecule is the final common effector of the signaling pathway. This is the first account of an organic inhibitor of the T cell Ca2+ current. Stimulation of T cells by externally applied PGE1 stimulated 125I efflux and activated a slowly developing membrane current. 4. 61 comments The tgAAVCF administration was well tolerated, without adverse respiratory events, and there was no evidence of enhanced inflammation in sinus histopathology or alterations in serum-neutralizing antibody titer to adeno-associated virus (AAV) capsid protein after vector administration. A total of 183 mutations were identified, including 14 different amino acid-changing novel variants. Ca2+ currents induced by receptor stimulation and Ca(2+)-ATPase inhibition were not additive. In this article we discuss the early phases of T-cell activation with an emphasis on receptor-associated signaling molecules, mobilization of Ca, and on the possible roles of Ca in signal transduction. She has served on the board of directors of several public and private companies, including . These sites represent the most common variants in Tay-Sachs disease, Bloom syndrome, Canavan disease, Niemann-Pick A, familial dysautonomia, torsion dystonia, mucolipidosis type IV, Fanconi anemia, Gaucher disease, factor XI deficiency, glycogen storage disease type 1a, maple syrup urine disease, nonsyndromic sensorineural hearing loss, familial Mediterranean fever, and glycogen storage disease type III. This study was conducted in Jurkat T cells to investigate the effects of A77 1726 on signal transduction pathways initiated by ligands of the T-cell receptor CD3 complex and to evaluate the effects of A77 1726 on nucleotide biosynthesis.Tritiated thymidine incorporation and cell counts quantitated cell proliferation. Encina Hall West Suite 100 Stanford, CA 94305-6044 Phone: 650-723-1806 Campus Map In conclusion, our results suggest that A2AR participates in regulation of airway C1 secretion via aCa2+-dependent signalling pathway, which involves CaMK and appears to be at least partially conserved in cystic fibrosis airway epithelial cells. Gardner recently. The role of calcium in the action of tumor necrosis factor (TNF) on human neutrophils is not clear. Nghiem, P., OLLICK, T., Gardner, P., Schulman, H. ACTIVATION OF CA2+ CURRENT IN JURKAT T-CELLS FOLLOWING THE DEPLETION OF CA2+ STORES BY MICROSOMAL CA2+-ATPASE INHIBITORS. View details for Web of Science ID A1993KR82200022. Phyllis Gardner knew from the moment the 19-year-old student started talking about her "brilliant" idea that it wouldn't work. A., Goeddel, D. V., Gardner, P. PROPERTIES OF CA CURRENTS ACTIVATED BY T-CELL RECEPTOR SIGNALING, CLONING AND ANALYSIS OF 2 NEW ISOFORMS OF MULTIFUNCTIONAL CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE - EXPRESSION IN MULTIPLE HUMAN TISSUES. 3. We demonstrate that intracellular release of inositol 1,4,5-trisphosphate (InsP3), either from stimulation of transfected human muscarinic receptors or from photolytic release of caged InsP3, activates whole cell Ca2+ current in the Jurkat T cell line. Addition of BAPTA (10 mM), a Ca2+ chelator, to the perfusion pipette also abolished the ADO-elicited Cl- current. It was 2002, and the student was a Stanford University sophomore. A., Nepomuceno, I. Schrijver, I., Ramalingam, S., Sankaran, R., Swanson, S., Dunlop, C. L., Keiles, S., Moss, R. B., Oehlert, J., Gardner, P., Wassman, E. R., Kammesheidt, A. She has previously served as Dean of Education. This review addresses the genetics of hearing loss, discusses the most commonly offered genetic assays for nonsyndromic hearing loss, with advantages and limitations, proposes a practical testing algorithm, and highlights current developments. The effect of Ca2+ ionophore on whole-cell Cl- currents is inhibited by a specific peptide inhibitor of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase). A., McDonald, T. V., Gardner, P. STIMULATION OF CHLORIDE SECRETION BY P-1 PURINOCEPTOR AGONISTS IN CYSTIC-FIBROSIS PHENOTYPE AIRWAY EPITHELIAL-CELL LINE CFPEO-. She has served on the board of directors of several public and private companies, including . 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. 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. We conclude that expression of mutant CFTR in human TCC is accompanied by ion channel dysfunction characteristic of the CF phenotype, and is accompanied by a reduction in IL-10 secretion after polyclonal activation. Thus, lymphocytes may be an accessible source of CF tissue for study of this defect, for cloning of the chloride channel complex, and for diagnosis of the disease. Sequence changes were identified in 11.7% and 10% of presbycusis and control alleles, respectively. 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. (1) A77 1726 dose-dependently inhibited the proliferation of Jurkat T cells (inhibitory concentration of 50% = 6 mumol/L); (2) A77 1726 did not decrease mobilization of intracellular Ca2+ stimulated by phytohemagglutinin or anti-CD3 monoclonal antibody; (3) A77 1726 did not inhibit interleukin-2 gene promoter activity in cells stimulated with ionomycin plus phorbol myristate acetate; (4) inhibition of cell proliferation by A77 1726 was antagonized by addition of uridine, cytidine, or 2(+)-deoxycytidine; (5) addition of uridine 24 hours after treatment with A77 1726 antagonized inhibition of proliferation; (6) A77 1726 was not antagonized by 2'-deoxyuridine, thymidine, adenosine, or guanosine. View details for Web of Science ID A1994PH25400057. 2. STANFORD, CA - MAY 24: Stanford University professor Phyllis Gardner poses for a portrait on May 24, 2019, in Stanford, Calif. Gardner's blunt criticism of Theranos and its disgraced founder . [1] [2] [3] B., Wagner, J. She attended the Slade School of Fine Art and was a suffragette when they met. There is also preliminary evidence that TCR/CD3 may structurally conform to G protein coupled receptors, i.e., having a core structure of seven alpha helical transmembrane spanning segments, a ligand recognition site, loci for regulatory phosphorylation, and a putative nucleotide binding site. 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. Cystic fibrosis (CF) is a common genetic disorder characterized by defective epithelial chloride transport and progressive lung disease. The Ca2+ signal can be further resolved at the level of the single cell into a series of repetitive oscillations between peak and trough levels with a period of 16-20 s. The oscillations may be part of a frequency-encoded signaling system. These findings suggest that two Ca2+/calmodulin-responsive enzymes, multifunctional CaM kinase and calcineurin, could mediate the divergent effects of Ca2+ signals in T-lymphocyte regulation. 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. Multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) is a mediator of calcium signals in diverse signaling pathways. View details for Web of Science ID 000083463500002. 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. A 48-h antisense treatment reduced the expression of CFTR protein as assayed by immunoprecipitation and autoradiography to 26% of the level in sense-treated T84 cells. Dr. Phyllis I. Gardner is an internist in Stanford, California. Among the presbycusis group, these solely occurred within the GJB2 and SLC26A4 genes. McDonald, T. V., NGHIEM, P. T., Gardner, P., Martens, C. L. PROSTAGLANDIN-E1 ACTIVATES A CHLORIDE CURRENT IN JURKAT-T LYMPHOCYTES VIA CAMP-DEPENDENT PROTEIN-KINASE. SCHUMANN, M. A., Gardner, P., Raffin, T. A. Wagner, J. Whole-cell recordings from JurkaT E6-1 human T-lymphocytes revealed two components of substance P action on the outward K+ current: (i) dose- and time-dependent reduction of current peak amplitude; and (ii) acceleration of the current inactivation rate. 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. IL-8 concentration rose in sinus fluids from affected sinuses. DBHQ stimulated 125I efflux and mobilized intracellular free Ca2+ in a dose-dependent manner. Professor of Medicine (Clinical Pharmacology) Medicine - Med/Clinical Pharmacology University - Faculty McDonald, T. V., Premack, B. A phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies. Spectrofluorescence of Indo/AM dye measured intracellular Ca2+ mobilization. Because hearing loss is a major public health concern and common at all ages, this test is suitable for follow-up after newborn hearing screening and for the detection of a genetic etiology in older children and adults.Comprehensive and relatively inexpensive genetic testing for sensorineural hearing loss will improve medical management for affected individuals and genetic counseling for their families. Addition of rhTNF alpha activated Cl- current in 80% of tested cells; the activated current was blocked by 10 microM 5-nitro-2-3-phenylpropylamino)benzoic acid, a Cl- channel blocker. This leads to production of inositol 1,4,5-trisphosphate, release of stored intracellular Ca, and activation of Ca-permeable plasma membrane channels. View details for Web of Science ID 000078432500017. This is a review of the application of microfabrication technologies, borrowed from the semiconductor industry, to drug delivery implants incorporating structures in the nanometer dimension. 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. This pathway is defective in cystic fibrosis-derived human cloned T cells. 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. Gardner recently opened up about her distrust and dislike . It seems likely that rapid progress will be made in our understanding of these areas through a combination of immunological, biochemical, and electrophysiological approaches. In addition, voltage-gated K+ channels, which closely resemble the delayed rectifier K+ channel of nerve and muscle, can be classified into three subtypes, according to their voltage dependence of activation, inactivation kinetics, and pharmacological sensitivity. Phospholipid bilayers composed of 1:1 w/w phosphotidylserine:phosphotidylethanolamine exposed to this toxin display discrete current flow events typical of transmembrane channels and consistent with the interpretation that this toxin acts by forming pores in phospholipid membranes. 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. Non-transformed, antigen-responsive CD4+ T cells cloned from healthy controls and CF patients homozygous or heterozygous for the delta F508 mutation transcribed CFTR mRNA and expressed immunoreactive cytoplasmic CFTR protein. DBHQ is a commercially available non-toxic synthetic compound chemically unrelated to THG and CPA. CFTR is required for the cAMP pathway but not for the calcium pathway. Nitric oxide, which is produced by cytokine-activated mononuclear cells, is thought to play an important role in inflammation and immunity. If you see your name among the Troy High School graduates, someone is looking for you! Support Lucile Packard Children's Hospital Stanford and child and maternal health. Lalonde, G., McDonald, T. V., Gardner, P., OHANLEY, P. D. A CAMP-REGULATED CHLORIDE CHANNEL IN LYMPHOCYTES THAT IS AFFECTED IN CYSTIC-FIBROSIS, TRIGGERING OF LYMPHOCYTES-T VIA EITHER T3-TI OR T11 SURFACE-STRUCTURES OPENS A VOLTAGE-INSENSITIVE PLASMA-MEMBRANE CALCIUM-PERMEABLE CHANNEL - REQUIREMENT FOR INTERLEUKIN-2 GENE-FUNCTION. The arrayed primer extension genotyping microarray carries 59 sequence variant detection sites, of which 53 are detectable bi-directionally. 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. View details for Web of Science ID A1992HD15400067. She worked within the hospitality management industry for well over 30 years. This hemolysin produces pores in membranes as demonstrated by osmotic protection studies using red blood cells and carbohydrate compounds of various molecular weights. The results suggest that the dihydropyridine Ca agonist Bay K 8644 interacts with both voltage-gated and receptor-operated Ca channels and also suggest potential strategies for development of a new class of immunomodulatory drugs. These results suggest that there is no relationship between P-gp and the chloride channel activated by cell swelling. 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. The molecular genetic basis for the majority of these patients remains obscure, however, because of the absence of associated clinical features in approximately 70% (ie, nonsyndromic hearing loss) of patients, genetic heterogeneity, and the lack of molecular genetic tests that can evaluate a large number of mutations across multiple genes.We report on the development of a diagnostic panel with 198 mutations underlying sensorineural (mostly nonsyndromic) hearing loss. Depletion of stored Ca2+ by either receptor stimulation or microsomal Ca(2+)-ATPase inhibition activated a low conductance, Ca(2+)-selective, non-voltage-activated membrane current. PHYLLIS STANKO OBITUARY. InsP3 may have its effect indirectly through depletion of Ca2+ stores, or directly with a plasma membrane-associated InsP3 receptor. In summary, this Phase II trial confirms the safety of tgAAVCF but provides little support of its efficacy in the within-patient controlled sinus study. When she told her professor Dr Phyllis Gardner about her idea, Gardner told her it was ambitious . In human lymphocytes and epithelial tissues, CaM kinase activates a chloride channel via a Ca(2+)-dependent pathway which is preserved in cystic fibrosis. Clinical manifestations include both pancreatic and pulmonary insufficiency. A prolonged (at least 2-4 hr) elevation of [Ca2+]i accompanies early T cell activation by TCR/CD3-specific ligands. In the Peyer's patches, a high level of expression was localized to epithelial cells, potentially M cells, overlying the lymphoid follicle domes. Premack, B. Phyllis Gardner Age: 68 Position: Professor of medicine at Stanford, board member at Revance Therapeutics and CohBar. The Stanford professor was one of the first people to doubt Holmes' credentials and products, dismissing Holmes' patch idea when she was a 19-year-old student at the university. The regulation of the channels by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in transformed B cells from CF patients is defective. Dose-dependent changes in TEPD responses to pharmacologic intervention were observed following treatments. We report here whole-cell patch clamp studies of normal and cystic fibrosis-derived airway epithelial cells showing that Cl- channel activation by Ca2+ is mediated by multifunctional Ca2+/calmodulin-dependent protein kinase. Beals, C. R., Sheridan, C. M., Turck, C. W., Gardner, P., Crabtree, G. R. Reduced IL-10 secretion by CD4(+) T lymphocytes expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR). STANFORD, CA - MAY 24: Stanford University professor Phyllis Gardner poses for a portrait on May 24, 2019, in Stanford, Calif. Gardner's blunt criticism of Theranos and its disgraced founder, Elizabeth Holmes, have made her a favorite among those who have closely followed the blood testing company's downfall. Bath-application of DBHQ induced an outwardly-rectifying whole-cell Cl- current, which was abolished by pipette addition of BAPTA (5 mM) or CaMK [273-302] (20 microM), an inhibitory peptide of multifunctional Ca2+/calmodulin-dependent protein kinase (CaMKII). 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). In this study, replication-defective adenoviral vectors were used to explore parameters that may be important in administering gene therapy vectors to the intestine. This panel, developed on a microarray, is capable of simultaneous evaluation of multiple mutations in 8 genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5 and the mitochondrial genes encoding 12S rRNA and tRNA-Ser[UCN]).The arrayed primer extension array for sensorineural hearing loss is based on a versatile platform technology and is a robust, cost-effective, and easily modifiable assay. She and Rupert Brooke had, on her side at least, a passionate relationship. Modulation of the voltage-gated K+ conductance in T-lymphocytes by substance P was examined. These results show that Ca2+ changes are associated with the effects of rhTNF alpha and that CaM kinase plays a role in the mechanism underlying rhTNF alpha-induced activation of Ca(2+)-activated Cl- current in human neutrophils. The identity of the amplified products was confirmed by hybridization to CFTR-specific probes and DNA sequencing. Schrijver, I., Kulm, M., Gardner, P. I., Pergament, E. P., Fiddler, M. B. (ABSTRACT TRUNCATED AT 400 WORDS), View details for Web of Science ID A1990DA09800009. View details for Web of Science ID A1991FH80200006. Various potentially confounding factors are discussed. Purification of the NF-AT kinase revealed that it is composed of a priming kinase activity and glycogen synthase kinase-3 (GSK-3). Thus, the control of [Ca2+]i remains coupled to TCR/CD3 function. View details for Web of Science ID A1994PN23700032, View details for PubMedCentralID PMC1510420. In addition, several other internal feedback controls on TCR/CD3 function, by CD4-induced tyrosine-specific phosphorylation of the CD3 zeta subunit, or on the Ca2+ signal, by extracellular Cl- or by GM1 gangliosides, are also postulated. This discrepancy is even more pronounced when such carrier screening panels are used for diagnostic purposes. View details for Web of Science ID A1995QV29100011. MED 299: Directed Reading in Medicine (Autumn, Winter, Spring, Summer) MED 280: Early Clinical Experience in Medicine (Autumn, Winter, Spring, Summer) Homozygous and compound heterozygous pathogenic mutations were exclusively seen in affected individuals. Expression of the CFTR protein is thought to be physiologically important only in exocrine epithelial cells. We demonstrate here that volume-regulated chloride-selective currents can be induced in cells with or without P-gp expression. There is also an associated K+ efflux and membrane hyperpolarization. View details for Web of Science ID A1994PH77400001. Lecturer in Management, Gradaute School of Business (2011 - Present) Lecturer, Department of Chemical Engineering (2009 - Present) Lecturer, Department of Chemical Engineering (2000 - 2003) Honors & Awards Fellow, American Institute of Medical and Biological Engineers (AIMBE) (2014 - Present) Member, National Academy of Engineering (2005 - Present) View details for Web of Science ID A1994NH08400029. 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. 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. 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 1. By use of whole-cell patch clamp recordings, we show that nitric oxide activates cystic fibrosis transmembrane conductance regulator CI- currents in normal human cloned T cells by a cGMP-dependent mechanism. Patch-clamp studies have identified a cAMP-dependent Cl- conductance in lymphocytes that is defectively regulated in cystic fibrosis. Overexpression of either P-gp or cystic fibrosis transmembrane conductance regulator, the protein product of the CF gene and another member of the ATP-dependent transporters, is associated with a hypotonicity-induced, rapid onset, transient current prior to onset of the volume-sensitive chloride-selective current, an apparent nonspecific effect related to the overexpression of an integral membrane protein. 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. A., COZENS, A. L., Schulman, H., Gruenert, D. C., Stryer, L., Gardner, P. PATCH CLAMP STUDIES OF LYMPHOCYTE-ACTIVATION, MODULATION OF MEMBRANE K+ CONDUCTANCE IN LYMPHOCYTES-T BY SUBSTANCE-P VIA A GTP-BINDING PROTEIN, IDENTIFICATION OF A HEMOLYSIN FROM ACTINOBACILLUS-PLEUROPNEUMONIAE AND CHARACTERIZATION OF ITS CHANNEL PROPERTIES IN PLANAR PHOSPHOLIPID-BILAYERS.
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