Two phases of zymogen granule lifetime in mouse pancreas: ghost granules linger after exocytosis of contents

Different cell types show widely divergent mechanisms and kinetics of exocytosis. We investigated these processes in pancreatic acinar cells by using video-rate 2-photon microscopy to image entry of extracellular dye into individual zymogen granules undergoing exocytosis. Fluorescence signals display two distinct phases; an initial peak that then decays over several seconds to a prolonged plateau. Several observations suggest that the first component reflects the binding of dye to the granule contents and their subsequent release into the acinar duct. These observations include: the peak/plateau fluorescence ratio differs between different dyes; the initial fluorescence decay mirrors the loss of granule contents as monitored by differential interference contrast microscopy; and the fall in vesicular fluorescence is accompanied by a rise in fluorescence in the adjacent duct lumen. We thus propose the use of extracellular fluorescent probes as a convenient means to monitor the kinetics of loss of proteinaceous content from secretory granules. In pancreatic acinar cells the fusion pore remains open much longer than required to ensure secretion of the granule contents, and instead the persistent empty 'ghost-granule' may act as a conduit to which secondary granules can fuse and release their contents by compound exocytosis.     

Role of Multiple Scouting Biopsies before Mohs Micrographic Surgery for Extramammary Paget's Disease

Background. Extramammary Paget's disease (EMPD) frequently extends subclinically, resulting in high recurrence rates after surgical excision. Mohs micrographic surgery (MMS) improves cure rates but may require time-consuming reexcision of subclinical extension. A mechanism to estimate the location and extent of subclinical extension would be helpful.
Objective. To describe and evaluate a technique for multiple scouting biopsies before MMS for EMPD.
Method. A retrospective review of patients at Mayo Clinic who had multiple scouting biopsies before MMS for EMPD without dermal invasion.
Technique. The clinical extent of EMPD is identified. The scouting biopsy sites are determined and documented with photographs. The scouting biopsy specimens are sent for permanent sections. The results of the scouting biopsies help guide the extent of the initial Mohs layer. The tumor is cleared with MMS. An additional 1 mm peripheral margin of tissue is usually submitted for permanent sections.
Results. Multiple scouting biopsies were done in five patients. Four of the five patients had at least one true-positive result. At least one true-negative result was obtained in all five patients. Two patients had at least one false-negative result.
Conclusion. Multiple scouting biopsies before MMS for EMPD without dermal invasion can be a beneficial adjuvant technique.
DAVID L. APPERT, MD, CLARK C. OTLEY, MD, P. KIM PHILLIPS, MD, AND RANDALL K. ROENIGK, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.     

Response of the unattached 218Po activity size distribution in H2O-SO2-N2 atmospheres.

The response of the unattached 218Po activity size distribution to variations in H2O and SO2 concentration was investigated in a high-purity N2 atmosphere. Lognormal size distributions were reconstructed from screen diffusion battery data using a random search and optimization procedure. For relative humidities of 1% to 90%, SO2 concentrations of 0-6 ppm, and residence times of 38 s, median diameters of the unattached mode ranged from 0.50 (+/- 0.04) to 0.80 (+/- 0.06) nm, corresponding to diffusion coefficients of 0.1-0.05 cm2 s-1. Increases in water vapor concentration resulted in an enhanced rate of ion neutralization and suppression of ion cluster formation. Decreases in cluster diameter with increasing humidity were therefore observed. Addition of SO2 at constant relative humidity resulted in an initial increase in diameter, with a subsequent decrease. Geometric standard deviations averaged 1.05 (+/- 0.01) to 1.06 (+/- 0.01) in all cases, with the unattached fraction comprising 83% to 88% of the total distribution. Results suggest that increases in water vapor concentration enhance neutralization in the immediate vicinity of the recoil path through water radiolysis. Conversion of OH to H2OSO4 on addition of SO2 provides a binary condensable phase capable of clustering around the ion at low relative humidities, increasing particle size. High H2O and SO2 concentrations enhance neutralization through electron scavenging and subsequent ion collision near the end of the recoil path, decreasing the number of available cluster sites and suppressing cluster formation. This reduction is more significant than the increasing size of the stable ion cluster, with increasing H2O and H2SO4 concentrations as predicted by Raes, resulting in decreases in both median diameter and distribution spread.     

用健康信念模式设计健康教育项目

根据健康信念模式,有4个关键因素会影响人们的行为改变.在设计健康教育项目时我们应该考虑每一个因素.无论一个人是采取预防行为还是开始一个治疗过程,他/她都会根据他们对每一个因素的认知来决定他们未来的行为.这4个因素分别是：易感性、严重性、益处和障碍.     

Studies of the human oropharyngeal airspaces using magnetic resonance imaging IV--the oropharyngeal retention effect for four inhalation delivery systems.

Magnetic resonance imaging (MRI) of the oropharyngeal region from 20 adult volunteers using four model inhalation devices (varying mouthpiece diameters, airflow resistances) and tidal breathing was carried out. Statistical analysis (convex hull method) selected 12 scans from 80 data sets representing the extremes of all dimensions in the population. Twelve physical mouth-throat models were made by stereolithography using the exact scan data. The aim was to produce models with varying dimensions to span the adult population, and to investigate if oropharyngeal dimensions affected throat retention for different delivery systems. In an in vitro analysis, the models were used to determine the retention effect of the oropharyngeal airspaces when drug aerosols were administered from four inhalation delivery systems: a pressurised metered dose inhaler (pMDI), two different dry powder inhalers (DPIs A and B), and a nebulizer. The aims of this work were to determine the key parameters governing mouth-throat retention and whether retention was dependent on the delivery system used. Characterizing the throat models by measuring 51 different dimensional variables enabled determination of the most influential variables for dose retention for each inhalation delivery system. Throat model retention was found to be dependent on the delivery system (pMDI approximately DPI(A) > DPI(B) > Neb.). The most influential variable was the total throat model volume. Throat models representing high, median, and low oropharyngeal filtration in healthy adults have been identified.     

Is the spectacle lens jack‐in‐the‐box phenomenon really due to the lenses?

The calculation of the extent of the ring scotoma around positive lenses, as conventionally taught to students of clinical optics, indicates that the scotoma is of a significant size. Using knife-edge lenses this study shows that the calculations are invalid due to the finite size of the eye's entrance pupil and in many instances the scotoma is shown not to exist. The effect noticed in clinical practice is probably largely due to the frame and the edging techniques used which add to the refractive scotoma which is present with high powered lenses, large apertures and/or small pupil sizes.