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Biomedical subjects

M Wu

Publications and source records attributed to M Wu.

At least 631 records · Page 35Linked to original sources

Intestinal uptake of macromolecules. IV.--The effect of pancreatic duct ligation on the breakdown of antigen and antigen-antibody complexes on the intestinal surface.

We have previously shown a consistent decrease in antigen absorption in vitro by ileal and jejunal gut sacs from orally or parenterally immunized rats in contrast to controls. In immunized rats, antigen appeared to be retained on the surface of the intestine and to be retained on the surface of the intestine and to undergo enhanced degradation by local proteases. This study was concerned with the role of pancreatic enzymes in degradation of antigen and antigen-antibody complexes. The breakdown of [125I]bovine serum albumin (BSA) by jejunal and ileal gut sacs from BSA-immunized, pancreatic duct-ligated rats was significantly decreased in comparison to that of BSA-immunized, sham-operated controls. Treatment of the immunized, pancreatic duct-ligated rats with pancreatic extracts prior to removal of the gut sacs, led to an increase in breakdown of [125I]BSA by the gut sacs in vitro. These findings suggest that pancreatic enzymes adsorbed to the surface of the intestine contribute to the proteolysis of antigens and antigen-antibody complexes at this site.

Animals↗

Intestinal uptake of macromolecules. III. Studies on the mechanism by which immunization interferes with antigen uptake.

The mechanism(s) whereby immunization interferes with the intestinal absorption of macromolecules has been examined. After repeated intraperitoneal injection of protein antigens emulsified in incomplete Freund's adjuvant into rats, everted gut sacs from these animals and controls were exposed to radiolabeled antigen in vitro. There was a significant decrease in absorption of antigen by gut sacs from immunized rats as compared to control rats. On further analysis, it was found that, in contrast to controls, gut sacs from immunized rats showed an increased initial adsorption of labeled antigen. Furthermore, gut sacs from immunized rats showed enhanced breakdown of labeled antigen on prolonged incubation. Following incubation, gut sacs were rinsed and the amount of radioactivity eluted was determined. More radioactivity was present in the first rinse fluid of gut sacs from immunized rats than in rinse fluid from controls. On density gradient ultracentrifugation of the former fluids, radioactivity was localized in the middle or bottom of the gradient, whereas radioactivity in the latter fluids was located at the top of the gradient. The rapidly sedimenting labeled antigen was co-precipitated in the reaction of rabbit anti-rat IgG1 and IgG1 protein, suggesting the presence of antigen-IgG1 antibody complexes in the rinse fluid. These findings suggest that in vitro, antigen becomes rapidly associated with antibodies present on the surface of the gut. Formation of antigen-antibody complexes seems to prevent binding of antigen to and subsquent pinocytosis by the intestinal epithelial cells. Antigen-antibody complexes retained in the muous coat of the gut may be degraded by local proteases. The findings in this study suggest an additional role for antibodies present on mucosal surfaces, i.e., protection against absorption of ingested proteins which have escaped normal digestion in the intestinal lumen.

Adsorption↗

Cardiovascular risk factors among children after a 2 1/2-year intervention-The CATCH Study.

BACKGROUND: Cardiovascular risk factors and related behaviors begin during youth. METHODS: As part of the Child and Adolescent Trial for Cardiovascular Health, 4,019 children from four states and representing multiple ethnic groups were measured for selected risk factors both at baseline and after 2(1/2) years of intervention. Common protocols were used for both examinations at the four sites. RESULTS: Overall, changes in obesity, blood pressure, and serum lipids in the intervention group, compared with the control group, were not statistically significant. Total cholesterol, the primary physiologic outcome measure, decreased by 1.3 mg/dl over time in the intervention group and by 0.9 mg/dl (P > 0.05) in the control group. Different risk factor patterns for boys and girls and among three ethnic groups were noted. CONCLUSIONS: Although the school-based program effected significant institutional changes in food service and physical education class and although the children made significant changes in eating and physical activity behaviors, these did not translate to significant changes in risk factors at these ages. These behavioral changes, however, if sustained into adulthood, have the potential to influence cardiovascular risk reduction.

Adolescent↗

Cell-specific delivery of bacteriophage-encapsidated ricin A chain.

We have used covalent coupling of deglycosylated ricin A chain (RAC) to the assembly initiation/translational repression RNA stem-loop (TR) of the bacteriophage MS2 to direct encapsulation of the toxin in bacteriophage capsids. Multiple copies of the TR-RAC conjugate can be incorporated into single capsid shells. The resultant particles can then be directed to specific cells by receptor-mediated endocytosis (RME) of complexes formed with anti-MS2 coat protein antibodies or by further covalent modification of the capsids by addition of human transferrin molecules. The results suggest that bacteriophage encapsulation and targeting is an efficient way to deliver toxins in a cell-specific fashion. The system may have widespread application in the field of targeted drug delivery, including antisense reagents.

Base Sequence↗