Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure

<p>Abstract</p> <p>Background</p> <p>Monoclonal free light chains (FLCs) frequently cause rapidly progressive renal failure in patients with multiple myeloma. Immunoassays which provide quantitative measurement of FLCs in serum, have now been adopted into screening algorithms for multiple myeloma and other lymphoproliferative disorders. The assays indicate monoclonal FLC production by the presence of an abnormal κ to λ FLC ratio (reference range 0.26–1.65). Previous work, however, has demonstrated that in patients with renal failure the FLC ratio can be increased above normal with no other evidence of monoclonal proteins suggesting that in this population the range should be extended (reference range 0.37–3.1). This study evaluated the diagnostic sensitivity and specificity of the immunoassays in patients with severe renal failure.</p> <p>Methods</p> <p>Sera from 142 patients with new dialysis-dependent renal failure were assessed by serum protein electrophoresis (SPE), FLC immunoassays and immunofixation electrophoresis. The sensitivity and specificity of the FLC ratio's published reference range was compared with the modified renal reference range for identifying patients with multiple myeloma; by receiver operating characteristic curve analysis.</p> <p>Results</p> <p>Forty one patients had a clinical diagnosis of multiple myeloma; all of these patients had abnormal serum FLC ratios. The modified FLC ratio range increased the specificity of the assays (from 93% to 99%), with no loss of sensitivity. Monoclonal FLCs were identified in the urine from 23 of 24 patients assessed.</p> <p>Conclusion</p> <p>Measurement of serum FLC concentrations and calculation of the serum κ/λ ratio is a convenient, sensitive and specific method for identifying monoclonal FLC production in patients with multiple myeloma and acute renal failure. Rapid diagnosis in these patients will allow early initiation of disease specific treatment, such as chemotherapy plus or minus therapies for direct removal of FLCs.</p

Polymeric human Fc-fusion proteins with modified effector functions

The success of Fc-fusion bio-therapeutics has spurred the development of other Fc-fusion products for treating and/or vaccinating against a range of diseases. We describe a method to modulate their function by converting them into well-defined stable polymers. This strategy resulted in cylindrical hexameric structures revealed by tapping mode atomic force microscopy (AFM). Polymeric Fc-fusions were significantly less immunogenic than their dimeric or monomeric counterparts, a result partly owing to their reduced ability to interact with critical Fc-receptors. However, in the absence of the fusion partner, polymeric IgG1-Fc molecules were capable of binding selectively to FcγRs, with significantly increased affinity owing to their increased valency, suggesting that these reagents may prove of immediate utility in the development of well-defined replacements for intravenous immunoglobulin (IVIG) therapy. Overall, these findings establish an effective IgG Fc-fusion based polymeric platform with which the therapeutic and vaccination applications of Fc-fusion immune-complexes can now be explored

Coastal Upwelling Supplies Oxygen-Depleted Water to the Columbia River Estuary

Low dissolved oxygen (DO) is a common feature of many estuarine and shallow-water environments, and is often attributed to anthropogenic nutrient enrichment from terrestrial-fluvial pathways. However, recent events in the U.S. Pacific Northwest have highlighted that wind-forced upwelling can cause naturally occurring low DO water to move onto the continental shelf, leading to mortalities of benthic fish and invertebrates. Coastal estuaries in the Pacific Northwest are strongly linked to ocean forcings, and here we report observations on the spatial and temporal patterns of oxygen concentration in the Columbia River estuary. Hydrographic measurements were made from transect (spatial survey) or anchor station (temporal survey) deployments over a variety of wind stresses and tidal states during the upwelling seasons of 2006 through 2008. During this period, biologically stressful levels of dissolved oxygen were observed to enter the Columbia River estuary from oceanic sources, with minimum values close to the hypoxic threshold of 2.0 mg L−1. Riverine water was consistently normoxic. Upwelling wind stress controlled the timing and magnitude of low DO events, while tidal-modulated estuarine circulation patterns influenced the spatial extent and duration of exposure to low DO water. Strong upwelling during neap tides produced the largest impact on the estuary. The observed oxygen concentrations likely had deleterious behavioral and physiological consequences for migrating juvenile salmon and benthic crabs. Based on a wind-forced supply mechanism, low DO events are probably common to the Columbia River and other regional estuaries and if conditions on the shelf deteriorate further, as observations and models predict, Pacific Northwest estuarine habitats could experience a decrease in environmental quality

Fish and mussels: importance of fish for freshwater mussel conservation

Co-extinctions are increasingly recognized as one of the major processes leading to the global biodiversity crisis, but there is still limited scientific evidence on the magnitude of potential impacts and causal mechanisms responsible for the decline of affiliate (dependent) species. Freshwater mussels (Bivalvia, Unionida), one of the most threatened faunal groups on Earth, need to pass through a parasitic larval (glochidia) phase using fishes as hosts to complete their life cycle. Here, we provide a synthesis of published evidence on the fish–mussel relationship to explore possible patterns in co-extinction risk and discuss the main threats affecting this interaction. We retrieved 205 publications until December 2015, most of which were performed in North America, completed under laboratory conditions and were aimed at characterizing the life cycle and/or determining the suitable fish hosts for freshwater mussels. Mussel species were reported to infest between one and 53 fish species, with some fish families (e.g., Cyprinidae and Percidae) being used more often as hosts than others. No relationship was found between the breadth of host use and the extinction risk of freshwater mussels. Very few studies focused on threats affecting the fish–mussel relationship, a knowledge gap that may impair the application of future conservation measures. Here, we identify a variety of threats that may negatively affect fish species, document and discuss the concomitant impacts on freshwater mussels, and suggest directions for future studies.The Portuguese Foundation for Science and Technology—FCT through POPH/FSE funds supported VM, MI and MLL under grants (SFRH/BD/108298/2015), (SFRH/BPD/90088/2012), (SFRH/BD/115728/2016), respectively. KD acknowledges the support from the Czech Science Foundation (13-05872S). RS acknowledges the support of the strategic programme UID/BIA/04050/2013 (POCI-01-0145- FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI). This study was conducted as part of the project FRESHCO: Multiple implications of invasive species on Freshwater Mussel co-extinction processes, supported by FCT (contract: PTDC/AGRFOR/1627/2014)

Transmitter-Specific Subsets of Sensory Elements in the Prosobranch Osphradium

Volume: 187Start Page: 174End Page: 18