Matrix-free calcium in isolated chromaffin vesicles

Isolated secretory vesicles from bovine adrenal medulla contain 80 nmol of Ca2+ and 25 nmol of Mg2+ per milligram of protein. As determined with a Ca2+-selective electrode, a further accumulation of about 160 nmol of Ca2+/mg of protein can be attained upon addition of the Ca2+ ionophore A23187. During this process protons are released from the vesicles, in exchange for Ca2+ ions, as indicated by the decrease of the pH in the incubation medium or the release of 9-aminoacridine previously taken up by the vesicles. Intravesicular Mg2+ is not released from the vesicles by A23 187, as determined by atomic emission spectroscopy. In the presence of N H Q , which causes the collapse of the secretory vesicle transmembrane proton gradient (ApH), Ca2+ uptake decreases. Under these conditions A23 187-mediated influx of Ca2+ and efflux of H+ cease at Ca2+ concentrations of about 4 pM. Below this concentration Ca2+ is even released from the vesicles. At the Ca2+ concentration at which no net flux of ions occurs the intravesicular matrix free Ca2+ equals the extravesicular free Ca2+. In the absence of NH4C1 we determined an intravesicular pH of 6.2. Under these conditions the Ca2+ influx ceases around 0.15 pM. From this value and the known pH across the vesicular membrane an intravesicular matrix free Ca2+ concentration of about 24 pM was calculated. This is within the same order of magnitude as the concentration of free Ca2+ in the vesicles determined in the presence of NH4C1. Calculation of the total Ca2+ present in the secretory vesicles gives an apparent intravesicular Ca2+ concentration of 40 mM, which is a factor of lo4 higher than the free intravesicular concentration of Ca2+. It can be concluded, therefore, that the concentration gradient of free Ca2+ across the secretory vesicle membrane in the intact chromaffin cells is probably small, which implies that less energy is required to accumulate and maintain Ca2+ within the vesicles than was previously anticipated

The Victorian Newsletter (Spring 1978)

The Victorian Newsletter has been sponsored for the Victorian Group of the Modern Language Association by New York University and Queens College, City University of New York. Effective immediately, however, editorial and business communication should be addressed to the new editor: Professor Ward Hellstrom, Department of English, University of Florida, Gainesville, Florida 32611

The workload of web-based consultations with atopic eczema patients at home

Abstract Background Atopic eczema is a chronic inflammatory non-contagious skin disease characterised by intensive itch and inflamed skin. Due to its chronic and relapsing course atopic eczema imposes a great burden on affected families. Review articles about home care telemedicine have indicated advantageous effects of home telehealth. However, few studies have investigated how home care telemedicine applications affect the workload of the clinician. Methods The use of a web-based counselling system was recorded through computerised logging. The doctor who answered the requests sent via the Internet recorded the amount of time needed for reading and answering 93 consecutive requests. Results The time needed by the physician to read and answer a request was less than 5 minutes in 60% of the cases. The doctor spent significantly more time to answer requests that had photographs attached compared to requests without photographs (P = 0.005). The time needed to answer requests received during the winter season (October-March) was significantly longer than the rest of the year (P = 0.023). There was no correlation between the answering time and the age of the patient. Conclusions Individual web-based follow-up of atopic eczema patients at home is feasible. The amount of time needed for the doctor to respond to a request from the patient appears to be small. The answering time seems to depend on whether photographs are supplied and also on seasonal variations of disease activity. Since the management of atopic eczema is complex involving many different types of treatments and educational aspects, we expect this type of communication to be useful also to other chronic disease patients requiring close follow-up.</p

Lung Function after the Minimal Invasive Pectus Excavatum Repair (Nuss Procedure)

Background The Nuss procedure was introduced at our center in 1999. The operation was mainly performed for cosmesis. Little information is available regarding the influence of this operation on lung function. Methods The aim of this study, a prospective analysis, was to analyze the effect of the Nuss procedure on lung function variables. Between 1999 and 2007 a total of 203 patients with pectus excavatum were treated with the Nuss procedure, of whom 145 (104 male, 41 female) were located at Emma Children’s Hospital. In the latter subset of consecutive patients, static lung function variables [total lung capacity (TLC), functional residual capacity (FRC), vital capacity (VC)] and dynamic lung function variables [forced expired volume in 1 s (FEV1), maximum expiratory flow (MEF50)] were performed using spirometry and body box measurements at four time points: prior to operation Some of these data were presented at the International Surgical Week

Progress in cystic fibrosis and the CF Therapeutics Development Network

Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised

Magnetic field exposure and long-term survival among children with leukaemia

We examined the association between magnetic field (MF) exposure and survival among children with acute lymphoblastic leukaemia (ALL) treated at 51 Pediatric Oncology Group centres between 1996 and 2001. Of 1672 potentially eligible children under treatment, 482 (29%) participated and personal 24-h MF measurements were obtained from 412 participants. A total of 386 children with ALL and 361 with B-precursor ALL were included in the analysis of event-free survival (time from diagnosis to first treatment failure, relapse, secondary malignancy, or death) and overall survival. After adjustment for risk group and socioeconomic status, the event-free survival hazard ratio (HR) for children with measurements ⩾0.3 μT was 1.9 (95% confidence interval (CI) 0.8, 4.9), compared to <0.1 μT. For survival, elevated HRs were found for children exposed to ⩾0.3 μT (multivariate HR=4.5, 95% CI 1.5–13.8) but based on only four deaths among 19 children. While risk was increased among children with exposures above 0.3 μT, the small numbers limited inferences for this finding