Mechanism for enhanced external transfer of dimeric IgA over pentameric IgM: studies of diffusion, binding to the human polymeric Ig receptor, and epithelial transcytosis

Transport of polymeric Igs (pIgA and pIgM) across secretory epithelia is mediated by the polymeric Ig receptor (pIgR), also known as the transmembrane secretory component. Compared with local production, external transfer of pIgA is favored 6- to 12-fold over that of pIgM on a molar basis. This transfer may be modulated at several levels: diffusion through matrix and basement membranes, ligand affinity for pIgR, and efficiency of epithelial transcytosis. To investigate these possibilities, we compared the ability of Madin-Darby canine kidney epithelial cells transfected with human pIgR to transport pIgA vs pIgM from the basolateral to the apical face, and examined the inhibitory effect of various filter types used for mounting of the monolayer. Binding data showed that pIgR bound pIgA and pIgM with similar affinity. Internalization of both ligands was fast and took place at similar rates; transcytosis was also found to be equally efficient at the molar level. Thus, the overall rate of transport across the epithelial monolayer was comparable for pIgA and pIgM, and was not further enhanced by ligand stimulation over a 20-fold increased concentration level. Conversely, pIgA had a considerable advantage over pIgM in passive diffusion assays performed in vitro. Moreover, in situ immunofluorescence staining showed retention of IgM over IgA and IgG in mucosal basement membrane zones, in contrast to the preferential epithelial uptake of IgA and, less so, IgM. The biologic consequences of the highly efficient epithelial pIg transport, and the diffusion advantage of pIgA over pIgM, are discussed in relation to the evolution and function of secretory Abs.     

Prophylactic Greenfield filters: acute complications and long-term follow-up

The efficacy of prophylactic vena caval filters (VCF) in reducing morbidity and mortality from pulmonary embolism (PE) in high-risk trauma patients has been shown, but minimal follow-up data is currently available. VCFs were prophylactically placed in 110 patients between August 1991 and June 1995. There was an early VCF complication rate of 7%. Twenty-two patients died; the remaining 88 patients formed the basis for the follow-up study. Forty-five patients were located and interviewed by phone, and 30 of these patients (34%) returned for evaluation. The mean follow-up time was 18 months (range, 4-42 months). There was no incidence of caval thrombosis on follow-up. Eleven patients had physical findings, and duplex evidence consistent with postphlebitic syndrome. An additional three patients had evidence of old deep venous thrombosis (DVT) by duplex, but no significant symptomatology. VCF are effective in preventing PE related deaths and have few major complications. The long-term morbidity associated with posttraumatic venous thrombosis is significant. This morbidity is related not to PE or VCF, but to the underlying DVT. Improved strategies against DVT are necessary.     

Finite Element Analysis of a Radioactive Tritium Patch and a Waste Heat Plume Observed Near the Pickering Nuclear Power Generating Station,Lake Ontario

Effluents from industrial outfalls often form a moving patch or a steady plume in the receiving water, depending on the duration of the release. Empirical studies of coastal diffusion have shown that the eddy diffusivity obeys a power law of the length scale of the patch or plume. By analyzing a moving patch of radioactive tritium concentration and a steady plume of waste heat, the one superimposing over the other as indicated by the observed data, it is found that the cross-flow eddy diffusivity for a given length scale of the patch is about twice as large as that of the plume. The analysis is based on a variable-grid finite element method, which is used to derive the flow field and also to simulate the transport and diffusion processes. The proposed method is found particularly suitable for domains with irregular coastal structures, such as water intakes and outfalls.     

Quality of life and productivity in nurses reporting migraine

Calcium phosphate bone cements (CPBCs) are osteotransductive, i.e. after implantation in bone they are transformed into new bone tissue. Furthermore, due to the fact that they are mouldable, their osteointegration is immediate. Their chemistry has been established previously. Some CPBCs contain amorphous calcium phosphate (ACP) and set by a sol-gel transition. The others are crystalline and can give as the reaction product dicalcium phosphate dihydrate (DCPD), calcium-deficient hydroxyapatite (CDHA), carbonated apatite (CA) or hydroxyapatite (HA). Mixed-type gypsum-DCPD cements are also described. In vivo rates of osteotransduction vary as follows: gypsum-DCPD > DCPD > CDHA approximately CA > HA. The osteotransduction of CDHA-type cements may be increased by adding dicalcium phosphate anhydrous (DCP) and/or CaCO3 to the cement powder. CPBCs can be used for healing of bone defects, bone augmentation and bone reconstruction. Incorporation of drugs like antibiotics and bone morphogenetic protein is envisaged. Load-bearing applications are allowed for CHDA-type, CA-type and HA-type CPBCs as they have a higher compressive strength than human trabecular bone (10 MPa).     

Adding backbone to protein folding: why proteins are polypeptides

It is argued that the chemical nature of the polypeptide backbone is the central determinant of the three-dimensional structures of proteins. The requirement that buried polar groups form intramolecular hydrogen bonds limits the fold of the backbone to the well known units of secondary structure while the amino acid sequence chooses among the set of conformations available to the backbone. 'Sidechain-only' models, based for example on hydrophobicity patterns, fail to account for the properties of the backbone and thus will have difficulty capturing essential features of a folding pathway. This is evident from the incorrect predictions they make for the conformations of the limiting cases of all-hydrophobic or all-polar sequences.     

History of Lake Ontario Contamination from the Niagara River by Sediment Radiodating and Chlorinated Hydrocarbon Analysis

Contamination of Lake Ontario by persistent organic compounds began with the development of the chemical industry along the Niagara River. These compounds are discharged to the river where they are scavenged from the water column by sedimenting particulates which in turn settle out in depositional areas of Lake Ontario. We have determined ²¹⁰Pb, ¹³⁷Cs, and chlorinated hydrocarbon profiles of sediment cores taken about 3 km from the mouth of the Niagara River. Age profiles of the sediments were constructed from the radionuclide measurements and used to determine historic trends of chlorinated hydrocarbon input to Lake Ontario. The historical record found in the sediments for chlorobenzenes, chlorotoluenes, hexachlorobutadiene, octachlorostyrene, mirex, and PCBs is in good agreement with known production and usage patterns of the chemicals. Pollution of Lake Ontario with chlorinated hydrocarbons from the Niagara River is still occurring, but the worst contamination of the lake occurred in the 1960s.