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Biomedical subjects

T Baxter

Publications and source records attributed to T Baxter.

25 records · Page 2Linked to original sources

Use of gene therapy to induce human-mouse xenogeneic chimerism.

BACKGROUND: Bone marrow transplantation (BMT) has been used in the laboratory to overcome the immunologic barriers to xenotransplantation and results in chimerism and specific tolerance to donor antigens in lethally irradiated mice. Clinically, BMT carries the considerable risks of graft-versus-host disease and graft failure. Retrovirus-mediated gene transfer could provide a means of introducing foreign major histocompatibility (MHC) genes into host bone marrow cells (BMC) and thus accomplish the immunologic goals of BMT, without the associated risks. METHODS: Using a Moloney virus-based vector, a replication defective retrovirus was constructed that contained a complementary DNA encoding the human MHC antigen HLA-A2. Three million C57BL/6 mouse BMC were cocultured for 48 hours with 1 x 10(6) HLA-A2 virus "producer" cells in the presence of 15% WEHI supernatant (interleukin-3) and 200 units/ml interleukin-6. Putatively infected BMC were then used at 2 to 3 x 10(6) BMC/animal to reconstitute lethally irradiated syngeneic mice. RESULTS: Twelve days after reconstitution, spleen colonies were found to have integrated the full-length retroviral sequences. Thirty days after BMT, the introduced DNA could be found in the bone marrow, thymus, and spleen, and approximately 5% of T cells in the spleen expressed the HLA-A2 surface antigen. CONCLUSIONS: These data show that xenogeneic MHC genes can be introduced and expressed in mouse hematopoietic cells in vivo and indicate that gene therapy potentially may be used in the future to manipulate the immune system to induce transplantation tolerance.

Animals↗

A multiple muscle strength testing protocol.

A quick test (QT) protocol was developed to allow for the rapid testing of multiple muscle groups in order to profile body strength. Maximum muscle strength was also obtained using a standard test (ST) protocol. The ST protocol consisted of three five-second trials with a one-minute rest between trials and no more than four muscle groups tested per day. The QT protocol allowed only a five-second rest between trials. Thirteen subjects were evaluated using both protocols. Subjects were positioned either sitting or supine, depending on the muscle groups being evaluated. Stabilization was provided to minimize substitution patterns. Measurements were obtained using a load cell and a computerized recording system. Using the QT protocol and testing 13 muscle groups in one session vs five sessions with the ST protocol resulted in an average reduction of 4% in strength values for the QT protocol. The results suggest that the clinical use of the QT protocol may not significantly reduce the accuracy of repeated measurements even though values obtained may be slightly lower than those obtained using the ST protocol.

Adult↗

The effect of omeprazole pre-treatment on rafts formed by reflux suppressant tablets containing alginate.

Alginate-based reflux suppressant preparations provide symptom relief by forming a physical barrier on top of the stomach contents in the form of a neutral floating gel or raft. This study investigated whether reduced acidity in the stomach brought about by omeprazole pre-treatment affected the formation and gastric residence time of alginate rafts. It was a balanced, cross-over study in 12 healthy non-patient volunteers following a single dose of two indium-111-labelled alginate tablets in the presence or absence of 3 days' pre-treatment with omeprazole. Raft formation and gastric residence, in the presence of a technetium-99m-labelled meal, were assessed by gamma scintigraphy for 3 h after alginate tablet administration. The relative raft-forming ability of alginate tablets after omeprazole compared with alginate tablets alone was 0.950 with 95% confidence intervals of 0.882 and 1.018. Pre-treatment and co-administration with omeprazole has no significant effect on the raft-forming ability of alginate tablets.

Adult↗