Addition of adenosine (ADO; 0.1-1 mM) markedly increased 125I efflux rate. View details for Web of Science ID 000260722000005. 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. 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. These assays suggest a pore diameter in the order of 2 nm. The patients were between ages 20 and 65 yr, with adult-onset sensorineural hearing loss of unknown etiology, and carried a clinical diagnosis of early presbycusis. About Phyllis Gardner, M.D. 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). HiDOHealth Collaborates with Stanford and Appoints Advisors - PRWeb View details for Web of Science ID A1989T048300039. Three channel types that may contribute to activation have also been described in B lymphocytes. We realize that a Troy High School year book may be hard to . After surgically accessing the intestine, an E1-, E3-deleted adenoviral vector encoding beta-galactosidase (beta-Gal) was directly injected into various regions of the small and large intestine of rats and rabbits. Intracellular administration of hydrolysis-resistant guanosine triphosphate (to persistently activate GTP-binding protein) and guanosine diphosphate (to competitively inhibit GTP-binding proteins) analogues mimicked and inhibited substance P-induced reduction of K+ conductance, respectively. We conclude that CFTR mRNA is expressed in lymphocytes, consistent with the cAMP regulation of chloride transport present in normal lymphocytes but defective in CF-derived lymphocytes. It is shown here that a chloride channel with kinetic and regulatory properties similar to those described for secretory epithelial cells is present in both T and B lymphocyte cell lines. View details for Web of Science ID A1988Q219900001, Department: Medicine - Med/Clinical Pharmacology, Genetic Analysis of Presbycusis by Arrayed Primer Extension. 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. While STa and guanylin bind to the same receptor guanylyl cyclase and raise cell cGMP, the signaling mechanism distal to cGMP remains controversial. Phyllis Gardner (6 October 1890 - 16 February 1939) was a writer, artist, and noted breeder of Irish Wolfhounds. Ca2+ currents induced by receptor stimulation and Ca(2+)-ATPase inhibition were not additive. View details for Web of Science ID 000078432500017. These results favour the involvement of A2AR. 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. Significant transduction of the tissue was observed and histochemical staining was used to identify enterocytes as the primary targets of gene transfer. The linear relationship of current amplitude to holding potential when examined over the -60 to +60 mV range indicates that this pore has a constant mean single channel conductance level of 350-400 pS. View details for Web of Science ID A1991GF80400001. Schrijver, I., Oitmaa, E., Metspalu, A., Gardner, P. Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics novel mutations and assessment of a population-specific mutation spectrum. The intestinal tract has many features that make it an attractive target for therapeutic gene transfer. A defect in regulation of a chloride channel appears to be the molecular basis for cystic fibrosis (CF), a common lethal genetic disease. Specific attenuation of interleukin-2 transcriptional induction occurs in Jurkat T cells following pretreatment with a Ca2+ ionophore. 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. MiMedx Announces Appointment of Phyllis Gardner, M.D. to 6. Further study is warranted for AAV vectors as they may prove useful for CFTR gene transfer and other in vivo gene transfer therapies. 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 Web of Science ID A1995RF90000002, View details for PubMedCentralID PMC398388. Hometown: Her father was a professor, so she grew up in college towns. Sinus CT scans were also useful in diagnosing recurrent sinusitis in this surrogate model of CF infectious exacerbations.CF sinusitis as a surrogate for lung disease is particularly well-suited for phase II clinical trials of gene transfer agents, with the potential for measuring clinical efficacy in relatively small numbers of patients over relatively short periods of time. Academic pgardner@stanford.edu Tel: (650) 387-9319 Fax: (650) 327-9755 Current Research and Scholarly Interests We are interested in the general process of signal transduction, focusing on the role that ion channels play in this process. 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. The names listed below are alumni who have been searched for on this site from Troy High Schoolin Fullerton, California . 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. Holmes wanted to build a patch that would scan the wearer for infections and release antibiotics. Dr. Phyllis I. Gardner, MD | Stanford, CA | Internist | US News Doctors Danny In The Valley: Dr Phyllis Gardner, Stanford professor and 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]. Site-directed mutagenesis of the predicted autoinhibitory domain yielded a mutant which was approximately 37% active in the absence of Ca2+/calmodulin, confirming the region as critical for autoregulation, and suggesting this mutant as a tool for studying the role of CaM kinase in nonneuronal tissues. 4. This channel presumably underlies the K+ efflux and membrane hyperpolarization that accompany the mitogen-induced increase in [Ca2+]i. 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 DBHQ (25 microM) caused a short-term rise in [Ca2+]i in the absence of ambient Ca2+, and a sustained elevation of [Ca2+]i in cell monolayers bathed in the efflux solution (1.2 mM Ca2+), which was largely attenuated by Ni2+ (5 mM). View details for Web of Science ID A1992JF85600026. Wagner, J. Because GSK-3 responds to signals initiated by Wnt and other ligands, NF-AT family members could be effectors of these pathways. Dr. Phyllis Gardner, MD is a board certified internist in Stanford, California. When tested, persistence was observed in one patient for 41 days and in another for 10 weeks. 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. It is unclear whether or not this type of Ca2+ channel is present in straight B-cell lines. We reexamined this hypothesis by use of whole-cell patch clamp recordings of three matched pairs of cell lines, which were either drug-sensitive or drug-resistant due to P-gp overexpression. MiMedx Announces Appointment of Phyllis Gardner, M.D. to For each patient, a dose of 100,000 replication units of tgAAVCF was administered to one maxillary sinus, while the contralateral maxillary sinus received a placebo treatment, thereby establishing an inpatient control. Further research promises to refine vector technology and bring CF gene therapy to the bedside. Several properties of the depletion-activated Ca2+ current suggest that it is carried by a novel type of Ca2+ channel rather than an electrogenic carrier or pump. InsP3 may have its effect indirectly through depletion of Ca2+ stores, or directly with a plasma membrane-associated InsP3 receptor. 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. P1 purinoceptor agonists like adenosine have been shown to stimulate Cl- transport in secretory epithelia. View details for Web of Science ID 000231054600008. She has served on the board of directors of several public and private companies, including . Ion channels, and ion fluxes in general, appear to regulate a wide variety of processes important to lymphocyte function in normal and disease states. IL-8 concentration rose in sinus fluids from affected sinuses. Premack, B. Cystic fibrosis (CF), a lethal disease common to Caucasians, is characterized by a defect in the CF transmembrane conductance regulator and the resulting defective cAMP-regulated Cl- secretion by epithelial cells. 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). Although CF occurs with the highest incidence in Caucasians, it also occurs in other ethnicities with variable frequency. (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. View details for Web of Science ID A1997WH48600017. Phyllis Gardner - Wikipedia 3. B., Shah, N., Messner, A. H., Moran, M. L., Norbash, A. M., Moss, R. B., Wine, J. J., Gardner, P. Adenovirus-mediated transduction of intestinal cells in vivo. 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. View details for Web of Science ID A1989R820000062. In this study we used 125I efflux and whole-cell patch-clamp studies to investigate whether prostaglandin E1 (PGE1), an agonist that generates intracellular cAMP in Jurkat T lymphocytes, activates a Cl- conductance. Individuals who carry two mild mutations in the GJB2 gene possibly have an increased risk of developing early presbycusis. CFTR involvement in cAMP regulation of Cl- conductance in lymphocytes is further supported by our demonstration of the presence of appropriately spliced CFTR mRNA segments in human B and T lymphocytes as detected by an optimized reverse-transcription and polymerase chain reaction approach. 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. 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. 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. AVESTRIA VENTURES-Phyllis Gardner View details for Web of Science ID A1992KF37500001. A., Gardner, P. RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR-ALPHA INDUCES CALCIUM OSCILLATION AND CALCIUM-ACTIVATED CHLORIDE CURRENT IN HUMAN NEUTROPHILS - THE ROLE OF CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE. Phyllis I Gardner | Departments | Stanford Directory Whole-cell patch clamp revealed that a 48-h antisense treatment of T84 and 56FHTE-8o- fetal tracheal epithelial cells reduced the cAMP-activated chloride current to approximately 10% of that in sense-treated cells. In murine myeloma and hybridoma cells, a voltage-gated Ca2+ channel similar to Ca2+ channels in nerve, heart, and muscle is present.