Potential for Immunoprotection of Pancreatic Islets by Covalent Modification with Poly(ethylene glycol)

Diabetes Mellitus is one of the predominant contributors to morbidity and mortality worldwide. Prior to the advent of insulin therapy, patients suffering from Type I diabetes generally did not survive past childhood. Even with insulin therapy, a physiologically normal insulin response to increased systemic glucose cannot be achieved. Pancreatic islet transplantation has been shown to restore the physiological response to glucose, but risks associated with chronic immune suppression outweigh the benefit of tighter glucose regulation. This study investigates the potential of covalent modification of pancreatic islets with poly(ethylene glycol) (PEG) to abrogate the immune response towards transplanted islets and eliminate the need for chronic immune suppression. Previous studies have shown that PEG can be covalently bound to islet extracellular matrix (ECM) and surface proteins with no adverse affect on islet viability or function. The goal of this study was to determine the effect of covalent PEG modification on binding of islet-specific antibody, and to determine whether or not PEG modification could prolong graft survival in vivo. By a novel adaptation of an enzyme-linked immunosorbent assay (ELISA) the amount of islet-specific antibody bound to unmodified or PEG-modified islets was compared semi-quantitatively. Islets treated with 40kD branched PEG-NHS bound significantly more antibody than untreated controls. Based on the student's paired t-test there was no statistically significant change in antibody binding between 5kD PEG-treated and unmodified islets, although 7 of 9 PEG treated groups in this experiment bound less antibody than the corresponding unmodified groups. For in vivo islet transplantation , there was no difference in graft survival observed between PEG-treated and untreated grafts. Although PEG treatment did not have an apparent effect on in vivo graft survival, the effects observed in the antibody binding experiment suggest that PEG does modify antibody binding and further investigation of this technique is warranted

Flagellar membrane association via interaction with lipid rafts

The eukaryotic flagellar membrane has a distinct composition from other domains of the plasmalemma. Our work shows that the specialized composition of the trypanosome flagellar membrane reflects increased concentrations of sterols and saturated fatty acids, correlating with direct observation of high liquid order by laurdan fluorescence microscopy. These findings indicate that the trypanosome flagellar membrane possesses high concentrations of lipid rafts: discrete regions of lateral heterogeneity in plasma membranes that serve to sequester and organize specialized protein complexes. Consistent with this, a dually acylated Ca(2+) sensor that is concentrated in the flagellum is found in detergent-resistant membranes and mislocalizes if the lipid rafts are disrupted. Detergent-extracted cells have discrete membrane patches localized on the surface of the flagellar axoneme, suggestive of intraflagellar transport particles. Together, these results provide biophysical and biochemical evidence to indicate that lipid rafts are enriched in the trypanosome flagellar membrane, providing a unique mechanism for flagellar protein localization and illustrating a novel means by which specialized cellular functions may be partitioned to discrete membrane domains

Aircraft remote sensing of soil moisture and hydrologic parameters, Taylor Creek, Florida, and Little River, Georgia, 1979 data report

Experiments were conducted to evaluate aircraft remote sensing techniques for hydrology in a wide range of physiographic and climatic regions using several sensor platforms. The data were collected in late 1978 and during 1979 in two humid areas--Taylor Creek, Fla., and Little River, Ga. Soil moisture measurements and climatic observations are presented as well as the remote sensing data collected using thermal infrared, passive microwave, and active microwave systems

Preliminary analysis of the sensitivity of AIRSAR images to soil moisture variations

Synthetic Aperture Radar (SAR) images acquired from various sources such as Shuttle Imaging Radar B (SIR-B) and airborne SAR (AIRSAR) have been analyzed for signatures of soil moisture. The SIR-B measurements have shown a strong correlation between measurements of surface soil moisture (0-5 cm) and the radar backscattering coefficient sigma(sup o). The AIRSAR measurements, however, indicated a lower sensitivity. In this study, an attempt has been made to investigate the causes for this reduced sensitivity

Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice

<div><p>Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice.</p></div