Sustained elevation of intracellular Ca2+ by cell surface receptors is often dependent on influx of Ca2+ across the plasma membrane through routes not involving voltage-gated Ca2+ channels. 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 hemolytic activity is associated with a 107-kDa band as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and confirmed by Western blotting and immunoprecipitation. New patients are welcome. The advent of universal newborn hearing screening in the United States and other countries, together with the identification of genes involved in the process of hearing, have led to an increase in both the need and opportunity for accurate molecular diagnosis of patients with hearing loss. 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. In the present study, we investigated whether P1 agonist-induced Cl- secretion is preserved in cystic fibrosis airway epithelium and which signalling mechanism is involved. Hearing loss has a genetic etiology in the majority of cases and is very common. These results suggest that PGE1, acting through PKA, activates a Cl- current in Jurkat T cells. The names listed below are alumni who have been searched for on this site from Troy High Schoolin Fullerton, California . Encina Hall West Suite 100 Stanford, CA 94305-6044 Phone: 650-723-1806 Campus Map Young, W., Chen, J., Jung, F., Gardner, P. Freeman Spogli Institute for International Studies, Institute for Computational and Mathematical Engineering (ICME), Institute for Human-Centered Artificial Intelligence (HAI), Institute for Stem Cell Biology and Regenerative Medicine, Stanford Institute for Economic Policy Research (SIEPR), Stanford Woods Institute for the Environment, Office of VP for University Human Resources, Office of Vice President for Business Affairs and Chief Financial Officer. Chao, A. C., ZIFFERBLATT, J. 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. 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. Wagner, J. Schrijver, I., Kulm, M., Gardner, P. I., Pergament, E. P., Fiddler, M. B. 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). Professor of Medicine (Clinical Pharmacology) Medicine - Med/Clinical Pharmacology University - Faculty View details for Web of Science ID 000083463500002. (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. Over one third of the mutations (27/85) occurred with a relative frequency >1%, which illustrates that the identified mutations are not all rare. 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. 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. 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. The mutation spectrum in Hispanics, however, remains poorly defined. Gardner recently. Purification of the NF-AT kinase revealed that it is composed of a priming kinase activity and glycogen synthase kinase-3 (GSK-3). This finding demonstrates the potential of enterocytes to serve as heterotopic sites for the synthesis of heterologous gene products that would be secreted into the lumen of the intestinal tract or into the bloodstream. We report here that normal human B-lymphoblasts display whole cell Cl- conductances induced by calcium-mediated pathways, volume regulation, and cAMP which are equivalent to currents described in epithelial cells. In the presence of costimulation, Ca2+ influx in T cells leads to activation (transcription of interleukin-2; ref. Transduction of these cells could have application in DNA-mediated oral vaccination. Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasians, primarily affecting epithelial tissues of the lung and gut. 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. Wagner, J. cAMP kinase has been shown to mediate the cAMP pathway for regulation of Cl- channels in lymphocytes, but the mediator of an alternative, Ca2+ pathway has not been identified. 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. 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. The maximal effects were seen at concentrations of 25-50 microM. 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. Support teaching, research, and patient care. 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. 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. Patch-clamp studies have identified a cAMP-dependent Cl- conductance in lymphocytes that is defectively regulated in cystic fibrosis. 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. A total of 183 mutations were identified, including 14 different amino acid-changing novel variants. Sinusitis recurred at a rate of 45% during one month of follow-up. A77 1726, the active metabolite of leflunomide, inhibits lymphocyte proliferation in vitro. (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. With intracellular application of the Ca2+ chelator 1,2-bis (2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (5 mM), the calmodulin antagonist (2 microM), CaM kinase II-(290-309), or the inhibitory peptide (10 microM), CaM kinase II-(273-302), the current was no longer activated by rhTNF alpha. We find that intracellular application of activated kinase and ATP activates a Cl- current similar to that activated by a Ca2+ ionophore, that peptide inhibitors of either the kinase or calmodulin block Ca2(+)-dependent activation of Cl- channels, and that a peptide inhibitor of protein kinase C does not block Ca2(+)-dependent activation. Nishimoto, I., Wagner, J. Chao, A. C., deSauvage, F. J., Dong, Y. J., Wagner, J. In the Ashkenazi Jewish population, serious and lethal genetic conditions occur with relatively high frequency. These results underscore the disparity in mutation identification between Caucasians and Hispanics and show utility for comprehensive diagnostic CFTR mutation analysis in this population. SCHUMANN, M. A., Gardner, P., Raffin, T. A. Phyllis Gardner Age: 68 Position: Professor of medicine at Stanford, board member at Revance Therapeutics and CohBar. Dr. Phyllis Gardner, MD is a board certified internist in Stanford, California. 2. Chung, S. C., McDonald, T. V., Gardner, P. VOLUME-ACTIVATED CHLORIDE CURRENT IS NOT RELATED TO P-GLYCOPROTEIN OVEREXPRESSION. She is survived by daughters Gina & Michelle as well as seven grandchildren, six great-grandchildren, and her last remaining sibling, Larry. Wagner, J. Phyllis Gardner. 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. She attended the Slade School of Fine Art and was a suffragette when they met. 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. View details for Web of Science ID A1995QV29100011. Hence, the cAMP and calcium pathways are separate. In the absence of costimulation, Ca2+ influx results in anergy (interleukin-2 transcriptional block) through an unknown mechanism. View details for Web of Science ID A1993KH62000095. A., Daddona, P., Gardner, P., Huang, M. T. Efficient and persistent gene transfer of AAV-CFTR in maxillary sinus. Simultaneous multigene mutation detection in patients with sensorineural hearing loss through a novel diagnostic microarray: A new approach for newborn screening follow-up. Her research centered on cardiac arrhythmias, ion channel biophysiology, cell biology, cystic . Although CF occurs with the highest incidence in Caucasians, it also occurs in other ethnicities with variable frequency. View details for Web of Science ID A1993KR82200022. Contact. Finally, a Ca2(+)-activated K+ channel in T cells has recently been described. View details for Web of Science ID A1991GF80400001. She is currently a tenured professor at the School of Medicine at Stanford University . Further research promises to refine vector technology and bring CF gene therapy to the bedside. Further study is warranted for AAV vectors as they may prove useful for CFTR gene transfer and other in vivo gene transfer therapies. Pretreatment of monolayers of CFPAC-1 cells with DBHQ for 4-5 min significantly increased the Ca(2+)-independent or autonomous activity of CaMKII assayed in the cell homogenates. 61 comments The mechanism of TCR-stimulated Ca2+ influx was studied in the Jurkat human T cell line using Ca2+ indicator dyes and whole-cell patch clamp. These results are consistent with the activation of Cl- secretion via a P1 purinoceptor. Lifetime resident of Fullerton, passed away on 11/18/21 in her home. 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. Gardner tried to. She was 78 years old. 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. 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. View details for Web of Science ID A1994NH08400029. 5. 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). Three channel types that may contribute to activation have also been described in B lymphocytes. 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. Several mutations in the selected disorders that are not prevalent per se in the Ashkenazi Jewish populations, as well pseudodeficiency alleles, are also included in the array. The channel appeared to be identical to the previously described voltage-insensitive, messenger-mediated, calcium-permeable channel involved in T cell activation. View details for Web of Science ID A1995TM55700002. 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). The transcription factor NF-AT responds to Ca2+-calcineurin signals by translocating to the nucleus, where it participates in the activation of early immune response genes. 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. 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. She received her medical degree from Harvard Medical School and has been in practice for more than 20 years. 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 human lymphocytes and epithelial tissues, CaM kinase activates a chloride channel via a Ca(2+)-dependent pathway which is preserved in cystic fibrosis. 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. Although CF-derived TCC preserved mitogen and antigen proliferative responses and specificity to tetanus toxoid epitopes, they selectively secreted approximately 45% less IL-10 compared with control TCC after activation with concanavalin A (Con A) (624 +/- 101 versus 1564 +/- 401 pg/ml per 10(6) cells, respectively; P = 0.04) or anti-CD3/phorbol ester (5148 +/- 1634 versus 11788 +/- 2390 pg/ml; P = 0.05). 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). 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. The rank order of potency of purinoceptor agonists in stimulating 125I efflux was ADO > AMP > ADP approximately equal to ATP. 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. 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. 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. Gardner, a medical professor at Stanford University, told Holmes that her idea for a microfluidic patch that tested blood and delivered medicine was not possible. 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. 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. She worked within the hospitality management industry for well over 30 years. View details for Web of Science ID 000260722000005. Addition of purified catalytic subunit of cAMP-dependent protein kinase (PKA) plus ATP to the recording pipette also activated a similar current, whereas internally applied Walsh inhibitor, the synthetic peptide inhibitor of PKA, blocked the PGE1 effect. 0 (0 ratings) Leave a review. B., Messner, A. H., Moran, M. L., Batson, E. P., DiMiceli, S., Brown, B. W., Desch, J. K., Norbash, A. M., Conrad, C. K., Guggino, W. B., Flotte, T. R., Wine, J. J., Carter, B. J., Reynolds, T. C., Moss, R. B., Gardner, P. Safety and biological efficacy of an adeno-associated virus vector cystic fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus. Significant transduction of the tissue was observed and histochemical staining was used to identify enterocytes as the primary targets of gene transfer. Specific attenuation of interleukin-2 transcriptional induction occurs in Jurkat T cells following pretreatment with a Ca2+ ionophore. A membrane-permeable cAMP analog mimicked the effect of PGE1, whereas intracellular application of a cAMP antagonist Rp-cAMP blocked the effect of PGE1. This is the first account of an organic inhibitor of the T cell Ca2+ 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. After more than a decade in conceptualisation and experimentation, four systems that have commercial potential are discussed: i) implantable microchips with on-demand microdosage for one or more therapeutic agents under internal control or external control using a wireless link; ii) nanopore pumps, implantable titanium pumps, consisting of a drug reservoir with a nanopore-release membrane, capable of delivering potent small or macromolecules at constant serum levels for sustained periods of time; iii) nanocages, microfabricated nanopore immunoisolation chambers for cellular implants, capable of natural feedback-controlled delivery of proteins and peptides; and iv) nanobuckets, micromachined silicon porous particles with drug-loading capacity and targeting ligands for localised delivery. 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. She is currently licensed to practice medicine in California. 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. (ABSTRACT TRUNCATED AT 400 WORDS), View details for Web of Science ID A1990DA09800009. 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. Thus, DBHQ appears to enhance Cl- channel activity via a Ca(2+)-dependent mechanism involving CaMKII. View details for Web of Science ID A1997WQ51300045. The identity of the amplified products was confirmed by hybridization to CFTR-specific probes and DNA sequencing. Although great strides have been made in the treatment of CF, it remains lethal, often by early adulthood. Stanford Hospital and Clinics. 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. It was 2002, and the student was a Stanford University sophomore. When she told her professor Dr Phyllis Gardner about her idea, Gardner told her it was ambitious . 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. Ca2+ influx induced by inositol 1,4,5-triphosphate (IP3)-coupled surface receptors (either the TCR or a heterologous muscarinic receptor) was compared with Ca2+ influx induced by inhibitors of the microsomal Ca(2+)-ATPase (thapsigargin, cyclopiazonic acid, di-tert-butylhydroquinone), which release stored Ca2+ without production of IP3. 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. 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). The Stanford Medicine Alumni Association presents Women in Medicine and Science, Phyllis Gardner - Like a Salmon Swimming Upstream Stanford Medicine Alumni Awards 2022: Marian Carlson 3. She graduated from Harvard University / School Of Medicine in 1976. 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. 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 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. We realize that a Troy High School year book may be hard to . View details for Web of Science ID A1991FH80200006. View details for Web of Science ID A1989AX58900003. However, newer therapies directed at the specific underlying defects have emerged. Academic [email protected] Tel: (650) 387-9319 Fax: (650) 327-9755. NFAT mediated gene transcription; modulations by kinases and phosphatases. . 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. 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. View details for Web of Science ID 000074207900007, View details for Web of Science ID 000074088900015, View details for Web of Science ID 000073201700014. These include resting ionic homeostasis and the more complex signaling events involved in activation, proliferation, cytotoxic function, and volume regulation. Cystic fibrosis C1-channels in epithelial cells and lymphocytes; associated signal transduction pathways and cell biological coupling mechanisms. Who Is Phyllis Gardner? Stimulation of human T-lymphocytes via either the surface T3-Ti antigen-major histocompatibility complex receptor complex or the T11 molecule results in clonal proliferation through a calcium-dependent mechanism. An alternative to pulmonary testing of new CF treatments is use of the maxillary sinuses as a surrogate model of CF lung disease. When transfected into Jurkat T cells, the gamma B cDNA encoded a functional kinase which cosedimented on sucrose gradients with endogenous T cell CaM kinase activity and formed a large multimeric enzyme. Specialties. 4. @stanford: Currently teaching. Recently, guanylin, an endogenous peptide with properties similar to STa, was identified. 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. 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. SK&F 96365 has no effect on Ca2+ stores release or K+ channels. [1] [2] [3] She trained in Internal Medicine at Massachusetts General Hospital, followed by a Chief Residency at Stanford University Hospital. Phyllis Gardner (6 October 1890 - 16 February 1939) was a writer, artist, and noted breeder of Irish Wolfhounds. 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. 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. B-lymphoblasts from CF-affected humans demonstrated defective Cl- conductance regulation by cAMP but preserved regulation by calcium-mediated and volume regulation mechanisms. The early clinical gene therapy therapy work, with gene introduction by both viral and nonviral vectors, is discussed. Wagner, J. View details for Web of Science ID A1989T048300039. A defect in regulation of a chloride channel appears to be the molecular basis for cystic fibrosis (CF), a common lethal genetic disease. 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 chloride ion transport defect has been described in human CF-derived lymphocytes; however, it has not been possible to detect CFTR mRNA in lymphocytes. The wider application of patch-clamp and microfluorimetry techniques to lymphocytes has helped to clarify some issues and raised many more. 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. These results suggest that CaM kinase mediates the Ca2+ pathway of Cl- channel activation. View details for Web of Science ID 000078432500017. But Cl- flux in cystic fibrosis cells, as in normal cells, can be activated by raising intracellular Ca2+ (refs 5-10). Phyllis Gardner, an American biologist, was born on July 7, 1950, and is well known for being one of the first to question and challenge Elizabeth Holmes' beliefs. 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. Phyllis I. Gardner, MD Director Dr. Phyllis Gardner has over 40 years of experience in academia, medicine and the healthcare industry. Dr. Gardner has spent more than 35 years in academia, medicine and industry. 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. View details for Web of Science ID A1992KF37500001. 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. Gardner recently opened up about her distrust and dislike . 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. Modulation of the voltage-gated K+ conductance in T-lymphocytes by substance P was examined. The expression of the three K+ channel subtypes varies with the cell's developmental state and functional class. A similar order of potency was seen in transformed cystic fibrosis nasal polyp cells, CFNPEo- (ADO > ATP > AMP > ADP).

Will Brian Cassidy Return To Svu, Jamel Brown Palm Coast, Articles P