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Biomedical subjects

D Grant

Publications and source records attributed to D Grant.

At least 199 records · Page 11Linked to original sources
PubMed1991

Heparin-polypeptide interaction. Near-i.r. spectroscopy in an anhydrous dispersant allows the involvement of polymer-associated water to be assessed.

Involvement of polymer-associated water in the interaction of heparin with poly-L-arginine and poly-L-lysine was studied by i.r. spectroscopy of complexes suspended in a non-aqueous dispersant. Movement of i.r. absorption bands due to heparin-associated water to lower frequencies upon polymer interaction indicates that hydrogen-bonding accompanies complexation. We suggest that this bonding includes water bridging between the interacting species, and that the resulting changes in water chemistry may affect the biological activity of such interacting macromolecules.

Heparin↗
PubMed1991

Infrared spectroscopy of heparins suggests that the region 750-950 cm-1 is sensitive to changes in iduronate residue ring conformation.

By careful definition of polymer environment, heparin i.r. spectra were examined in a region (750-950 cm-1) in which sulphate half-ester absorptions occur. Changes seen in this region when metal ion-heparin complexes are converted into heparinic acid, when heparin is carboxy-group-reduced and when various concentrations of Li(+)-heparin are examined are tentatively interpreted in terms of changes in the ring conformation of iduronate residues.

Chemical Phenomena↗
PubMed1991

Refined technique for intestinal transplantation in the rat.

Unlike other solid organ transplants, intestinal transplantation (IT) remains a highly experimental procedure. Rejection, sepsis, and graft-versus-host disease have been the major barriers to successful IT in humans. These problems can be studied in the rat model, but this requires a reliable surgical technique that will produce high survival rates and excellent graft function. Herein, we review 400 consecutive IT in rats and describe important technical aspects of surgery. Technical modifications that have helped to reduce the morbidity after IT in rats include 1) minimizing mechanical and ischemic injuries to grafts during the donor procedure, 2) marking the portal vein and aortic conduit with sutures to ensure correct orientation of the graft, 3) using a macaroni noodle to stent the intestinal anastomosis, and 4) administering large volumes of crystalloid to maintain a normal blood pressure during the donor and recipient surgeries. The survival rate in 298 rats with accessory, heterotopic grafts was 90%. The survival rate in 102 rats with orthotopic (in continuity) graft (OIT) was 86%. Rats have survived more than 500 days after OIT, maintaining normal weights, intestinal function, and intestinal histology.

Anastomosis, Surgical↗
PubMed1991

Scatter factor stimulates migration of vascular endothelium and capillary-like tube formation.

Scatter factors (SFs) are heat- and trypsin-sensitive cytokines secreted by fibroblastic and vascular smooth muscle cell lines which stimulate motility of normal epithelium, carcinoma cells, and vascular endothelium. Human and mouse SFs have been purified and identified as 90 kD heterodimeric proteins consisting of heavy (58 kD) and light (31 kD) disulfide-bonded subunits. Partial amino acid sequence data from SF-derived tryptic peptides indicate marked sequence homology with hepatocyte growth factors, suggesting a common multigene family. In this chapter we describe the regulation by SF of vascular endothelial cell chemotaxis and chemokinesis; migration from microcarrier beads to flat surfaces; invasion through porous filters coated with reconstituted basement membrane; secretion of plasminogen activator; and in vitro capillary-like tube formation on a basement membrane surface.

Animals↗
PubMed1991

Mechanisms of rejection during OKT3 therapy: propagation and characterization of CD3 resistant allospecific cytotoxic T cells from a rejecting liver allograft.

Allograft rejection remains the single largest impediment to success in the field of transplantation. While OKT3 therapy has proven to be a significant advancement, many grafts are still lost. Late treatment, subtherapeutic OKT3 levels, anti-OKT3 antibodies, and OKT3-induced class II antigen expression are possible explanations. To determine the mechanism of OKT3 resistant rejection we propagated and characterized infiltrating T cells from the biopsy of a liver transplant patient who was rejecting while on prophylactic OKT3. The T lymphocytes demonstrated allospecific proliferation and interleukin 2 (IL2) production and showed a high degree of cytolysis of donor splenocytes. CD3 epsilon monoclonal antibodies (Mab) in concentrations up to 100 micrograms/ml did not inhibit lysis. In contrast, T lymphocytes derived from rejecting allografts of patients receiving cyclosporine and prednisone were readily inhibited from killing by CD3 epsilon Mab at doses of 1 microgram/ml. Furthermore, allospecific proliferation and IL2 production were not inhibited in the OKT3-treated patient by the addition of CD3 epsilon MaB. Incomplete modulation of the CD3-TCR complex was noted after a 72-hr incubation with CD3 epsilon Mab. The T cells did demonstrate other intact CD3-mediated functions such as a rise in intracellular calcium and CD3-dependent cytotoxicity. These results should alert clinicians that CD3 resistant cytotoxic T cells can emerge during OKT3 therapy and may cause rejection. Immunotherapy that targets additional cell surface structures may be of benefit.

Antibodies, Monoclonal↗