Stable expression of α1-antitrypsin Portland in MDA-MB-231 cells increased MT1-MMP and MMP-9 levels, but reduced tumour progression.

The membrane bound matrix metalloproteinase MT1-MMP plays roles in modulating cell movement, independent of its abilities to remodel the extracellular matrix. Unlike many MMPs, MT1-MMP is activated in the Golgi prior to secretion by a pro-protein convertase, primarily furin. Regulation of the activation of pro-MT1-MMP has been methodically investigated, as altering the level of the active protein has broad implications in both activating other pro-MMPs, including pro-MMP-2, and many subsequent remodelling events. Our previous work in MCF-7 cells has demonstrated that modest, and not extremely high, levels of active MT1-MMP manifests into altered cell morphology and movement. At this low but optimal amount of MT1-MMP protein, changes to MT1-MMP levels are always mirrored by MMP-9 and pERK levels, and always opposite to MMP-2 levels. In this study, stable expression of the furin inhibitor α1-antitrypsin Portland (α1-PDX) in MDA-MB-231 cells increased overall MT1-MMP levels, but cells maintained a 21% proportion of pro-MT1-MMP. The increase in MT1-MMP was mirrored by increases in MMP-9 and pERK, but a decrease in MMP-2. These changes were associated with increased NF-κB transcription. In vitro analysis showed that α1-PDX decreased cell protrusions and migration, and this manifested as decreased tumourigenesis when examined in vivo using a chick CAM assay.

Reinfusion of discard blood from venous access devices.

PURPOSE/OBJECTIVES: To determine if clots are present in the initial 10 ml of blood routinely discarded from venous access devices (VADs) prior to blood sampling, and to determine if clots form in the discard blood specimen during the five minutes required to complete blood specimen sampling. DESIGN: A pretest/post-test design. SETTING: A large, mid-Atlantic research institution. SAMPLE: A convenience sample of 50 adult patients with cancer (27 males and 23 females) with a median age of 60. A large sampling size variation existed among the different VADs. METHOD: Two 5 ml discard specimens were drawn into separate syringes. Syringe #1 was filtered immediately, and syringe #2 was filtered after a five-minute dwell time. Both samples were filtered through a 40 micron filter. MAIN RESEARCH VARIABLE: The presence or absence of clots. FINDINGS: Fifty percent (n = 25) of the VADs had clots present on the filter from syringe #1. The clots varied in length, width, depth, and diameter, which precluded a consistent measurement. The investigators were able to measure either the diameter or length, depending on the shape of the clots. The majority of the clots (n = 17) appeared to be shaped like the lumen of a catheter and varied from 0.1 cm to 1.2 cm in length. Six clots were round and varied in diameter from 1.6 mm to 2.8 mm. Only 4% (n = 2) of the VADs had clots in syringe #2, but those clots were much larger, measuring 8.3 mm and 18.4 mm. CONCLUSIONS: The study addresses concerns of the investigators regarding the clinical practice of reinfusing discard blood obtained from VADs. Whether the clots present in the catheter and their reinfusion represent a significant risk to patient outcome is unclear. IMPLICATIONS FOR NURSING PRACTICE: Until further research is conducted and the degree of risk can be better defined, methods of drawing blood that require reinfusion of discard blood from VADs are not recommended.

Polyphosphoinositide hydrolysis in response to light stimulation of rat and chick retina and retinal rod outer segments.

Phosphoinositides of chick and rat retina were labelled with [3H]inositol. Exposure of retinal preparations to light for 30 s caused loss of labelled phosphatidylinositol 4,5-bisphosphate and to a smaller extent of the other phosphoinositides. Similar light-induced changes were seen when rod outer segment preparations were used and, when these were illuminated in calcium-free media, phosphatidylinositol 4,5-bisphosphate was the only lipid affected. No inositol 1,4,5-trisphosphate was seen after either 30 s or 5 s of illumination of retina or 30 s illumination of rod outer segments. It is concluded that this compound plays no direct part in vertebrate photoreceptor light transduction, though phosphoinositide metabolism might relate to adaptation mechanisms.