phyllis gardner stanford

By means of path clamp recording and associated cell and molecular biological techniques, we have studied:1. A prospective, randomized, double-blind, placebo-controlled, within-subjects, phase II clinical trial of the effect AAV-CFTR on clinical recurrence of sinusitis will determine the clinical efficacy of AAV gene therapy for CF. 3. In human lymphocytes and epithelial tissues, CaM kinase activates a chloride channel via a Ca(2+)-dependent pathway which is preserved in cystic fibrosis. Gardner and. Nishimoto, I., Wagner, J. Bacterial cultures and increased sinus leukocytes corroborated recurrent sinusitis. The intestinal tract has many features that make it an attractive target for therapeutic gene transfer. DBHQ is a commercially available non-toxic synthetic compound chemically unrelated to THG and CPA. 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. 4. Stanford University professor Phyllis Gardner poses for a portrait on A defect in regulation of a chloride channel appears to be the molecular basis for cystic fibrosis (CF), a common lethal genetic disease. 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. Phyllis Gardner (clinical pharmacologist) - Wikipedia 3. Stanford's Phyllis Gardner Opens Up About Elizabeth Holmes Specialties. About Phyllis Gardner, M.D. Ca2+ currents induced by receptor stimulation and Ca(2+)-ATPase inhibition were not additive. Dr. Phyllis Gardner, MD, is an Internal Medicine specialist practicing in Stanford, CA with 47 years of experience. Dr. Gardner has spent more than 35 years in academia, medicine and industry. Gardner tried to. She sits on the Harvard Medical School Board of Fellows and the boards of biotechnology companies. View details for Web of Science ID 000260722000005. 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. 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. The mutation spectrum in Hispanics, however, remains poorly defined. The effects of purinoceptor agonists on Cl- secretion were examined in a transformed cystic fibrosis airway phenotype epithelial cell line, CFPEo-. Furthermore, currents flowing through Ca2+-permeable channels are apparently autoregulated, as inward conductance is abolished by elevation of Ca2+ concentration in the bathing solution. Photos from After the Downfall: What Elizabeth Holmes and the Theranos These results suggest that PGE1, acting through PKA, activates a Cl- current in Jurkat T cells. These include resting ionic homeostasis and the more complex signaling events involved in activation, proliferation, cytotoxic function, and volume regulation. Stanford Hospital and Clinics. Moss, R. B., BOCIAN, R. C., Hsu, Y. P., Dong, Y. J., Kemna, M., Wei, T., Gardner, P. Mechanism of the antiproliferative action of leflunomide - A77 1726, the active metabolite of leflunomide, does not block T-cell receptor-mediated signal transduction but its antiproliferative effects are antagonized by pyrimidine nucleosides. View details for Web of Science ID A1991FH80200006. The role of calcium in the action of tumor necrosis factor (TNF) on human neutrophils is not clear. Stanford professor Phyllis Gardner, MD, has been an outspoken skeptic of Elizabeth Holmes, and her now defunct company Theranos for years. She is survived by daughters Gina & Michelle as well as seven grandchildren, six great-grandchildren, and her last remaining sibling, Larry. With fluorescent cytometry, using the visible wavelength calcium probe, fluo-3, and patch clamping, we investigated whether TNF induces cytosolic free Ca2+ changes and Ca(2+)-activated Cl- current, respectively. The Ca2+ current was reversibly blocked by > 90% with 0.3 mM Cd2+, whereas the same concentration of Ni2+ or Co2+ blocked only 50 to 60% of the current. 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). A., Moran, M. L., Messner, A. H., DAIFUKU, R., Conrad, C. K., Reynolds, T., Guggino, W. B., Moss, R. B., Carter, B. J., Wine, J. J., Flotte, T. R., Gardner, P. Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. 300 Pasteur Dr Stanford, CA 94305. This pathway is defective in cystic fibrosis-derived human cloned T cells. 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. Assessing the biological activity and clinical efficacy of gene therapy is critically important in cystic fibrosis (CF). The conductance saturated when external Ca2+ was raised (Kd approximately 2 mM) and became highly permeable to monovalent cations when external Ca2+ was lowered to below 100 nM, much as has been observed for some voltage-gated Ca2+ channels. Wagner, J. She has previously served as Dean of Education. 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. The names listed below are alumni who have been searched for on this site from Troy High Schoolin Fullerton, California . 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. 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. A., Schulman, H., Gardner, P. ACTIVATION OF CHLORIDE CHANNELS IN NORMAL AND CYSTIC-FIBROSIS AIRWAY EPITHELIAL-CELLS BY MULTIFUNCTIONAL CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE. We conclude that generation of InsP3 is sufficient to activate Ca(2+)-selective channels in the plasma membrane of T cells. Wagner, J. DBHQ stimulated 125I efflux and mobilized intracellular free Ca2+ in a dose-dependent manner. 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. 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. Foreman, P. K., Wainwright, M. J., Alicke, B., Kovesdi, I., Wickham, T. J., Smith, J. G., Meier-Davis, S., Fix, J. 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. Each of the systems, along with future trends in microfabrication manufacturing, limitations and possibilities, are discussed. This Stanford Professor Tried To Stop Elizabeth Holmes - Refinery29 New patients are welcome. View details for Web of Science ID A1995RY95400014. Dose-dependent changes in TEPD responses to pharmacologic intervention were observed following treatments. She saw through Elizabeth Holmes. Now Stanford professor is star in A., Nepomuceno, I. 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) Three channel types that may contribute to activation have also been described in B lymphocytes. 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. Because GSK-3 responds to signals initiated by Wnt and other ligands, NF-AT family members could be effectors of these pathways. Recently, guanylin, an endogenous peptide with properties similar to STa, was identified. The intracellular application of the control peptide (10 microM), CaM kinase II-(284-302), or the protein kinase C (PKC) inhibitory, PKC-(19-36), or control, [Glu27]PKC-(19-36), peptide (5 microM) did not block the rhTNF alpha-induced Cl- current. Cystic fibrosis (CF), which is due to mutations in the cystic fibrosis transmembrane conductance regulator gene, is a common life-shortening disease. Theranos - News and updates on Elizabeth Holmes's failed company 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). 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. View details for Web of Science ID A1993KN53300018. In contrast, the calcium-activated chloride current was not affected by antisense treatment. View details for Web of Science ID A1994PN23700032, View details for PubMedCentralID PMC1510420. [1] [2] [3] 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). Recent national guidelines suggest that all couples contemplating pregnancy should be informed of molecular screening for CF carrier status for purposes of genetic counseling. SK&F 96365 has no effect on Ca2+ stores release or K+ channels. Register to let other graduates of Troy High School find and contact you. Maldonado, D., Schumann, M., Nghiem, P., Dong, Y., Gardner, P. REGULATION OF CL- CHANNELS BY MULTIFUNCTIONAL CAM KINASE. Cystic fibrosis C1-channels in epithelial cells and lymphocytes; associated signal transduction pathways and cell biological coupling mechanisms. Administration of an adenoviral vector encoding a secreted alkaline phosphatase to the lumen resulted in expression and secretion of this gene product into the circulation. View details for Web of Science ID A1995RF90000002, View details for PubMedCentralID PMC398388. 2. View details for DOI 10.1586/14737159.6.3.375, View details for Web of Science ID 000237916000010. Addition of BAPTA (10 mM), a Ca2+ chelator, to the perfusion pipette also abolished the ADO-elicited Cl- current. The maximal effects were seen at concentrations of 25-50 microM. We used RNase protection of this variable region to reveal the level of expression of gamma B and gamma C CaM kinase mRNAs in nine human tissues and cell lines. Preclinical and clinical research has lead to the rapid development of a variety of vectors designed to correct the basic defect in CF, including adenovirus, adeno-associated virus, and liposomes. 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. 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. In T-cells, a number of important kinases, phosphatases, and cytoskeleton-modulating enzymes are functionally Ca dependent but have no Ca-binding domains and therefore must sense changes in the cytoplasmic Ca level through interactions with Ca-binding proteins. Phyllis Gardner - Stanford University T-cell receptor signalling activates multifunctional CaM kinase. CFTR is required for the cAMP pathway but not for the calcium pathway. It seems likely that rapid progress will be made in our understanding of these areas through a combination of immunological, biochemical, and electrophysiological approaches. The channel appeared to be identical to the previously described voltage-insensitive, messenger-mediated, calcium-permeable channel involved in T cell activation. Using CF sinusitis as a surrogate model for testing clinical efficacy of new treatments is attractive because CF upper respiratory disease is similar to the lower respiratory disease with respect to electrophysiology and microbiology.Sinusitis recurrence in untreated sinuses was analyzed during a prospective, randomized, unblinded, dose-escalation, within-subjects, phase I clinical trial of the adeno-associated virus mediated cystic fibrosis transmembrane conductance regulator (AAV-CFTR) gene transfer.Clinical symptoms combined with sinus endoscopy proved useful in the diagnosis of unilateral and bilateral sinusitis recurrence. Dr. Phyllis Gardner, MD, Internal Medicine | Stanford, CA - WebMD Phyllis Gardner - Wikipedia 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. About Dr. Phyllis Gardner. This action was blocked by substituting Cs+ for K+ in the recording pipette and by the substance P antagonist. The regulation of the channels by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in transformed B cells from CF patients is defective. IL-8 concentration rose in sinus fluids from affected sinuses. Addition of adenosine (ADO; 0.1-1 mM) markedly increased 125I efflux rate. She attended Stanford University, where she first came up with the idea for her company, Theranos. 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. Phyllis Gardner (pictured), a professor of medicine at Stanford, criticized Elizabeth Holmes' blood testing company long before fraud charges were brought against her. Whole cell voltage clamp recordings indicate that the current is carried by a Ca(2+)-selective channel that resembles T-type voltage-gated Ca2+ channels in relative conductance of different cation species. Thus, the control of [Ca2+]i remains coupled to TCR/CD3 function. View details for Web of Science ID 000083463500002. Howard Rosen's Profile | Stanford Profiles This leads to production of inositol 1,4,5-trisphosphate, release of stored intracellular Ca, and activation of Ca-permeable plasma membrane channels. Chao, A. C., deSauvage, F. J., Dong, Y. J., Wagner, J. 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. It is unclear whether or not this type of Ca2+ channel is present in straight B-cell lines. When she told her professor Dr Phyllis Gardner about her idea, Gardner told her it was ambitious . View details for Web of Science ID A1994NM61500008. 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. Over one third of the mutations (27/85) occurred with a relative frequency >1%, which illustrates that the identified mutations are not all rare. This is the first account of an organic inhibitor of the T cell Ca2+ current. Expression of the CFTR protein is thought to be physiologically important only in exocrine epithelial cells. 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. It is possible that disruption of IL-10-mediated anti-inflammatory homeostasis may contribute to early onset sustained inflammation in CF airways. She's a professor of medicine at Stanford and a former partner in a health care venture capital firm. AVESTRIA VENTURES-Phyllis Gardner It has been suggested that P-glycoprotein (P-gp), an ATP-dependent transporter responsible for classical multidrug resistance, is also a volume-regulated chloride channel. A group of 257 self-identified Hispanics with clinical manifestations consistent with CF were studied by temporal temperature gradient electrophoresis and/or DNA sequencing. Exclusion criteria comprised known causes of hearing loss such as significant noise exposure, trauma, ototoxic medication, neoplasm, and congenital infection or syndrome, as well as congenital or pediatric onset. Rodriguez-Paris, J., Ballay, C., Inserra, M., Stidham, K., Colen, T., Roberson, J., Gardner, P., Schrijver, I. View details for Web of Science ID A1988Q219900001, Department: Medicine - Med/Clinical Pharmacology, Genetic Analysis of Presbycusis by Arrayed Primer Extension. 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. Simultaneous multigene mutation detection in patients with sensorineural hearing loss through a novel diagnostic microarray: A new approach for newborn screening follow-up. The recombinant gamma B isoform displayed two phases of autophosphorylation characteristic of CaM kinases, including the phase which converts it to a partially Ca(2+)-independent species. 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. Comprehensive arrayed primer extension array for the detection of 59 sequence variants in 15 conditions prevalent among the (Ashkenazi) Jewish population. (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. 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. 0 (0 ratings) Leave a review. Premack, B. In the presence of costimulation, Ca2+ influx in T cells leads to activation (transcription of interleukin-2; ref. 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 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. 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. In this study, replication-defective adenoviral vectors were used to explore parameters that may be important in administering gene therapy vectors to the intestine. View details for Web of Science ID A1993KR82200022. In murine myeloma and hybridoma cells, a voltage-gated Ca2+ channel similar to Ca2+ channels in nerve, heart, and muscle is present. 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. About Phyllis Gardner, M.D. A., Nepomuceno, I. View details for Web of Science ID A1994NH08400029. 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. Using the Hereditary Hearing Loss arrayed primer extension (APEX) array, which contains 198 mutations across 8 hearing loss-associated genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5, 12S-rRNA, and tRNA Ser), we compared the frequency of sequence variants in 94 individuals with early presbycusis to 50 unaffected controls and aimed to identify possible genetic contributors. Contact | Political Science - Stanford University 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 wider application of patch-clamp and microfluorimetry techniques to lymphocytes has helped to clarify some issues and raised many more. Phyllis Gardner Now: Where is Ex-Stanford Dean Today? Update 'Dropout' offers little new on Elizabeth Holmes; you'll still be hooked The antisense oligomers were a pair of adjacent 18-mers complementary to nucleotides 1-18 and 19-36 of CFTR mRNA. Hearing loss has a genetic etiology in the majority of cases and is very common. 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.

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