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.     

Skin protection against methylmethacrylate

Ordinary surgical rubber gloves are penetrated by methylmethacrylate monomer (MMA) in less than 1 minute, as demonstrated by gas chromatographic measurements. A three-layered PVP glove, 0.07 mm thick - consisting of an outer layer of polyethylene, an intermediary layer of ethylene vinyl alcohol copolymer, and an inner layer of polyethylene - was impervious for 20 minutes, whereas a viton-butyl rubber glove, 0.27 mm thick, was impervious for 15 minutes.

The PVP glove is recommended to orthopedic surgeons, nurses, and other handling acrylic bone cements to avoid sensitization, and is especially recommended to persons with known contact allergy to MMA.     

Review of case reports of inadvertent intrathecal administration of vincristine: Recommendations to reduce occurrence

Vincristine has been in clinical use for over 40 years with initial publication of the results from successful trials in 1962. Catastrophic neurotoxicity has been associated with the administration of vincristine directly into the cerebrospinal fluid (CSF). Since the first case in 1968 there have been numerous other instances, of which 23 have been reported in the literature. Of these cases 18 resulted in death. The most prominent damage on autopsy was generally in the spinal cord, brain stem and cerebellum, with severity tending to be greater in the neurons adjacent to the CSF. Fatalities appeared due to a progressive ascending myeloencephalopathy. Early recognition and immediate treatment with CSF drainage and intrathecal exchange appears to be the only intervention that has improved patient survival. The volume of injection, dose and time from the incident until the ventriculo‐lumbar washout appear critical, as these factors might contribute to the extent of drug distribution in the CNS. Although several antidotes for vincristine have been suggested, including folinic acid and glutamic acid, supportive evidence for their effectiveness is scant. Several recommendations regarding prevention of this catastrophic event have been proposed.     

<Emphasis Type="Italic">Bcl11b</Emphasis>mutations identified in murine lymphomas increase the proliferation rate of hematopoietic progenitor cells

Background  

The telomeric region of mouse chromosome 12 has previously shown frequent allelic loss in murine lymphoma. The Bcl11b gene has been identified and suggested as a candidate tumor suppressor gene within this region. In this study, we aimed to elucidate whether Bcl11b is mutated in lymphomas with allelic loss, and whether the mutations we detected conferred any effect on cell proliferation and apoptosis.     

Factors determining the ability of parents to effectively administer intramuscular adrenaline to food allergic children

Intramuscular adrenaline is the treatment of choice for food-related anaphylactic reactions. Although auto-injectable adrenaline devices are routinely prescribed for patients at risk of serious reactions, previous studies have shown that only one-third to one and a half of patients or their carers are able to properly use these devices. The aim of this study was to determine which factors are most strongly associated with the effective use of these devices. A 122 children with food allergies who had previously been prescribed EpiPens and were attending a single specialist pediatric allergy center in the UK. were studied prospectively. A 69% of parents were unable to use the EpiPen, did not have it available, or did not know when it should be administered. A prior practical demonstration was associated with a 4-5 fold greater chance that parents would be able to use the device (p < 0.005). Prior consultation with an allergy specialist rather than a general physician, and parents who independently sought additional information from the national self-help allergy organization were also four to six times more likely to be competent with these devices (p < 0.005). The study clearly shows that for EpiPens to be used safely and effectively it is essential to educate the carer at the time the device is prescribed.     

Growth hormone signalling: sprouting links between pathways, human genetics and therapeutic options.

Our molecular understanding of growth hormone-induced signal transduction has improved significantly over the past decades. At the same time, human population genetics and the analysis of genetically engineered animals have led to the discovery of genes that control specific aspects of the overall growth process. Although, currently, growth disorders are still diagnosed and treated on empirical bases, it might soon be possible to stratify patients predominantly by genetic defect, with treatment based on our molecular understanding of the role of the affected gene in the disease.