scholarly journals David Christopher Gadsby. 26 March 1947—9 March 2019

2020 ◽  
Vol 68 ◽  
pp. 175-193
Author(s):  
Christopher Miller

Over nearly five decades, David Christopher Gadsby pioneered biophysical research that advanced our mechanistic understanding of ion-transporting proteins in biological membranes. His passion for hands-on do-it-yourself electrophysiology, his depth of analytical rigor, and his idiosyncratic scientific aesthetic expanded the edge of discovery in two areas: the electrical character of the Na + pump, and the molecular workings of ‘cystic fibrosis transmembrane regulator’ (CFTR), the chloride ion channel whose mutations cause cystic fibrosis. His approach was flavoured by an appreciation for common underlying features between these ostensibly distinct types of membrane-transport systems. While David's focus was first on the basic molecular biophysics of a problem, he was always attuned to implications of his discoveries for human health. Based in New York at The Rockefeller University throughout his independent scientific career, and at the Marine Biological Laboratory in Woods Hole, Massachusetts, as a squid-season research-scientist, he was proficient in wrestling with problems spanning a wide swath of membrane biology: from determinants of the cardiac electrical waveform, to microsecond-timescale ionic currents in squid axons, to details of structure–mechanism relations in membrane pump and ion-channel proteins. He wore his eminence lightly and never distanced himself from the laboratory, where he often performed experiments with his own hands right up to his retirement. His reserved scientific personality, which demanded equally from his colleagues and himself immaculate data, unclouded logic, and substantive pertinence to the issues at hand, contrasted with his palpable joy in a good experiment and in his sea-loving life outside the lab.

Nature ◽  
1991 ◽  
Vol 354 (6354) ◽  
pp. 526-528 ◽  
Author(s):  
Wilfried Dalemans ◽  
Pascal Barbry ◽  
Guy Champigny ◽  
Sophie Jallat ◽  
Sophie Jallat ◽  
...  

JMS SKIMS ◽  
2015 ◽  
Vol 18 (2) ◽  
pp. 134-137
Author(s):  
Manzoor Raina ◽  
Mosin S Khan ◽  
Abdul H Raina ◽  
Mudassir Makhdoomi ◽  
Syed Mudassar

Cystic fibrosis (CF) is one of the most lethal, autosomal recessive, monogenic disorder that presents as a multisystem disease with significant morbidity and mortality in all parts of the world caused due to an abnormal transport of chloride ions across the apical membranes of epithelial cells. This autosomal recessive genetic disorder is caused by mutations of the CF transmembrane conductance regulator (CFTR) gene on chromosome 7 q31.2 1. The CFTR gene encodes the CFTR chloride-ion channel that is an essential component of epithelial ion transport systems in many organs, including the lungs, pancreas, intestinal tract, hepatobilliary tract, vas deferens and sweat glands. Cystic fibrosis (CF) affects exocrine gland function that involves multiple organ systems. Classical CF is characterized by progressive lung disease, pancreatic dysfunction, elevated sweat chloride  electrolyte, meconium ileus and male infertility and associated complications in untreated patients 2. JMS 2015; 18(2):134-137


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Emily DiMango ◽  
Kaitlyn Simpson ◽  
Elizabeth Menten ◽  
Claire Keating ◽  
Weijia Fan ◽  
...  

Abstract Background Evidence is conflicting regarding differential health outcomes in racial and ethnic minorities with cystic fibrosis (CF), a rare genetic disease affecting approximately 28,000 Americans. We performed a cross-sectional analysis of health outcomes in Black/Latinx patients compared with non-Hispanic Caucasian patients cared for in a CF center in New York City. Adult patients enrolled in the CF Foundation Patient Registry at the Columbia University Adult CF Program and seen at least once during 2019 were included. Health metrics were compared between Black/Latinx and non-Hispanic Caucasian patients. Results 262 patients were eligible. 39 patients (15%) identified as Black/Latinx or non-Hispanic Caucasian. Descriptive statistics are reported with mean (standard deviation). Current age was 35.9 (13.3) years for non-Hispanic Caucasian and 32.0 (9.3) years for Black/Latinx patients (p = 0.087). Age of diagnosis did not differ between groups; 9.56 (15.96) years versus 11.59 (15.8) years for non-Hispanic Caucasian versus Black/Latinx respectively (p = 0.464). Pulmonary function, measured as mean forced expiratory volume in one second (FEV1) was 70.6 (22.5) percent predicted in non-Hispanic Caucasian versus 59.50 (27.9) percent predicted in Black/Latinx patients (p = 0.010). Number of visits to the CF clinic were similar between groups. When controlled for age, gender, co-morbidities, median income, and insurance status, there was a continued association between minority status and lower FEV1. Conclusions Minorities with CF have significantly lower pulmonary function, the major marker of survival, than non-Hispanic Caucasians, even when controlled for a variety of demographic and socioeconomic factors that are known to affect health status in CF. Significant health disparities based on race and ethnicity exist at a single CF center in New York City, despite apparent similarities in access to guideline based care at an accredited CF Center. This data confirms the importance of design of culturally appropriate preventative and management strategies to better understand how to direct interventions to this vulnerable population with a rare disease.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Christopher Wasson ◽  
Rebecca Ross ◽  
Ruth Morton ◽  
Jamel Mankouri ◽  
Francesco Del Galdo

Abstract Background/Aims  The intracellular chloride ion channel CLIC4 mediates the activation of cancer associated fibroblasts. Interestingly, systemic sclerosis (SSc) fibroblasts display a number of similar properties to cancer associated fibroblasts. Tissue fibrosis in SSc is driven by active fibroblasts (myofibroblasts). Therefore in this study we investigated the role of CLIC4 in SSc fibroblast activation. Methods  Dermal fibroblasts were obtained from full thickness skin biopsies from SSc patients (early-diffuse). RNA and protein were collected from the fibroblasts and CLIC4 transcript and protein levels were assessed by qPCR and western blot. SSc patient fibroblasts were treated with the chloride ion channel inhibitors NPPB and IAA-94. Results  CLIC4 was found to be expressed at significantly higher levels in SSc patients fibroblasts compared to healthy controls, at both the transcript (3.7 fold) and protein (1.7 fold) levels. Inhibition of the TGF-β signalling pathway led to reduced CLIC4 expression in SSc fibroblasts, confirming this pathway as the main driver of CLIC4 expression. Finally, treatment of SSc fibroblasts with small molecule inhibitors that target the channel led to reduced expression of the myofibroblast markers collagen type 1 and alpha-smooth muscle actin, suggesting a direct role for CLIC4 in SSc associated skin fibrosis. Conclusion  We have identified a novel role for CLIC4 in SSc myofibroblast activation, which further strengthen the similarities between SSc fibroblasts and cancer associated fibroblasts. Furthermore this study highlights this channel as a novel target for therapeutic intervention. Disclosure  C. Wasson: None. R. Ross: None. R. Morton: None. J. Mankouri: None. F. Del Galdo: None.


1981 ◽  
Vol 59 (12) ◽  
pp. 1734-1744 ◽  
Author(s):  
Thomas M. Fyles ◽  
Virginia A. Malik-Diemer ◽  
Dennis M. Whitfield

An artificial membrane system based on a series of macrocyclic polyether carriers (crown ethers) is described. Under the influence of a proton gradient the carriers move alkali metal ions from basic to acidic solution through a chloroform membrane phase. Transport occurs against the concentration gradient of the transported ion as a result of a coupled counterflow of protons. Different transport behaviors are observed depending upon the metal ion concentration. At high metal ion concentration the amount transported is a linear function of time; at lower metal ion concentration the amount transported is a complex function of time which may be described as the result of a pair of consecutive first order processes. Effects of metal ion, carrier, and proton concentration on transport rate are considered. The rate increases with increasing metal ion or carrier concentration but is essentially independent of the pH of either aqueous phase. Increased lipophilicity of the carrier also results in a rate increase. Carriers derived from 18-crown-6 transport potassium selectively and all ions more rapidly than 15-crown-5 derivatives which are, however, selective for sodium. The overall efficiency of the system is discussed in terms of competing "leak" reactions, either of cations from the basic phase or of anions from the acidic phase.


PEDIATRICS ◽  
1961 ◽  
Vol 27 (2) ◽  
pp. 343-344

Cystic Fibrosis: 16 mm., color, sound, showing time 28 minutes. Prepared in 1959 by Henry B. Bruyn, M.D., Jackson T. Crane, M.D., and Howard L. Steinbach, M.D., San Francisco. Procurable on loan (service change $4) from Motion Picture Library, American Medical Association, 535 N. Dearborn St., Chicago 10. In this film there is a clear presentation of cystic fibrosis beginning with the discovery of it in 1938 and going through the history of the disease. The familial and recessive hereditary characteristics are discussed. There is also an excellent discussion of symptoms, the incidence of occurrence, and the various forms in which the disease might present itself. A brief case summary is given indicating the multiple diagnoses which may be made before the correct one is given. It is an excellent review of the physicopathology of the disease and the various tests that can be done to prove the presence of cystic fibrosis. A short resume of therapy such as diet, medication, immunization, and emotional problems is given. The photography and sound production are extremely good, and the film is highly recommended for pediatricians, general practitioners, house officers, and medical students. It's Wonderful Being A Girl: 16 mm., color, sound, showing time 19 minutes. Produced in 1959 by Audio Productions Inc., for Personal Products Corporation, Milltown, N.J. Procurable on loan or purchase ($77) from Audio Productions, Inc., 630 9th Ave., New York. The purpose of this film is to encourage a healthful knowledge of the menstrual process and positive attitudes for girls who are just beginning to menstruate. On her 14th birthday, Linda Brown decides that it's wonderful to be a girl growing up, It's wonderful to have parties and dates, make new friendships, learn new skills, and develop your talents. It's wonderful to know about yourself, recognize your bodily changes, and understand what menstruation is and how to live with it happily. This film story covers a year of Linda's life and shows how she arrives at these happy conclusions. She learns from her mother what to expect when menstruation occurs. She begins to scorn the old wives' tales she has heard and the superstitious attitudes she has seen. When she begins to menstruate, she finds that it need not hamper her in successfully meeting the challenges of everyday life. At school a teacher's thorough explanation, brought to life in colored, animated drawings, provides Linda with the important facts about how she became the girl she is: the origin of life in a single cell, the changing physical characteristics of a girl in her early teens, and the purpose and psychological processes of menstruation. Discussions in the class reveal that a girl's menstrual periods need not limit her activities. Through her own social experiences with girls and boys in her hobby club, at the school picnic, at parties and in other activities, Linda discovers that regular meals, sleep, and exercise help her to take menstruation in stride with the other normal problems and pleasures of growing up. This film is to be commended for its emphasis on the fact that menstruation is a perfectly normal process in the life of girls. It helps to create proper attitudes for girls who may have some problems in adjusting to menstruation, particularly in the beginning. The story is well developed and the film is effective because it closely approximates life situations for girls in this age group. Good mother-daughter and teacher-student relationships are demonstrated. It is unfortunate that the sponsor included a brief scene about their product. This may restrict use of the film in some schools. This picture is recommended for the audiences for which it was intended, namely, girls in elementary and junior high school. It would also be of interest to parents, teachers, and those in teacher training.


PEDIATRICS ◽  
1962 ◽  
Vol 30 (6) ◽  
pp. 1018-1018

Cystic Fibrosis—NCFRF. 16 mm., color, sound, showing time 32 minutes. Produced in 1961 by Samuel L. Schulman for the National Cystic Fibrosis Research Foundation, medical supervision by Giulio J. Barbero, M.D. Philadelphia. Procurable on purchase from National Cystic Fibrosis Research Foundation, 521 Fifth Avenue, New York City 17. Procurable on loan from American Medical Association, Motion Picture Library, 535 N. Dearborn Street, Chicago 10. This film has been prepared to aid physicians in making a correct diagnosis and to instruct them in the techniques currently being used to prolong life in cases of cystic fibrosis. Following the introductoy remarks there is a good discussion of the presenting symptoms, the differential diagnosis, the multiple system involvement, hereditary aspects, therapy, and prognosis. The film brings out well the panexocrine involvement, the clinical variability, and the fact that the disease is not an all or none phenomenon but rather a disease of all grades of severity and is a disease in which no single test is applicable to the exclusion of others. The diagrams and patient demonstrations are good. Perhaps too much review of older methods of therapy and diagnosis is given, but this serves as a background for the newer recommended procedures. More emphasis could have been given to the tremendous burden, both financial and emotional, this disease is on parents. This is an excellent instructive film and it emphasizes the many problems of cystic fibrosis as related to the diagnostic tools available and to forms of therapy. The photography and sound are satisfactory. It is recommended for pediatricians, general practitioners, house staff, and medical students.


2018 ◽  
Vol 31 (12) ◽  
pp. 1332-1338 ◽  
Author(s):  
Rong Xu ◽  
Yuan Xiao ◽  
Yan Liu ◽  
Bo Wang ◽  
Xing Li ◽  
...  

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