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Biomedical subjects

B A Solomon

Publications and source records attributed to B A Solomon.

At least 55 records · Page 3Linked to original sources

Long-term plasma glucose normalization in experimental diabetic rats with macroencapsulated implants of benign human insulinomas.

Permselective tubular membranes (1 mm i.d.) were filled with fragments of nine freshly resected human insulinomas, closed at both ends, and implanted in the peritoneal cavity of 30 streptozocin-induced diabetic rats. In 14 animals, nonfasting plasma glucose (PG) and insulin levels were normalized by these immunoprotected transplants for up to 1 yr (PG from 520 +/- 12 to 142 +/- 3 mg/100 ml; insulin from 6 +/- 0.5 to 44 +/- 3 microU/ml). These animals showed the same weight gain after 12 mo of observation as 20 controls. The remaining 16 animals showed an incomplete or transient correction of their diabetes and survived 4-6 mo, versus less than 8 wk in untreated animals. Removal of the membrane-encapsulated insulin-secreting tissue from 8 successfully treated rats led to hyperglycemia and death within 10 days. Histology and electron microscopy of insulinoma tissue retrieved after long-term implantation showed functionally active endocrine cells and no evidence of graft rejection. In vitro perifusion gave similar results for encapsulated and nonencapsulated insulinoma tissue. The amount of insulin secreted was quite variable, and responsiveness of the insulinoma to changes in glucose concentration of the surrounding medium was observed in three out of the five tumors studied. These observations establish the effectiveness of immunoseparation by a synthetic membrane in a pancreatic xenograft model.

Adenoma, Islet Cell↗

Biohybrid artificial pancreas. Long-term insulin secretion by devices seeded with canine islets.

Long-term insulin secretion was investigated in seven biohybrid capillary devices seeded with canine islets. Approximately 50,000 islets could be isolated from a single canine pancreas using collagenase digestion in conjunction with the recently described Velcro technique. Devices were perfused with tissue culture medium 199 containing 300 mg/dl glucose. Insulin secretion fell during the first 1-2 days of culture from approximately 18 to 6 U/day. After 3-4 wk of perfusion, however, there was a gradual rise in insulin output that reached greater than 15 U/day after 7 wk. Insulin output eventually stabilized at 18-20 U/day. Two of these devices were studied for 80 and 86 days, respectively, and continued to secrete these same amounts of insulin. Glucose-induced insulin release was studied after 1 and 4 wk of culture and was well preserved.

Animals↗

Anisotropic membranes with carboxypeptidase G1.

Anisotropic polysulfone membranes were prepared with carboxypeptidase G1 embedded in the polymer structure. The enzymatically active flat and hollow-fiber membranes were obtained by precipitating the polymer from solution in an organic mixture in which an aqueous solution of the enzyme had been dispersed. The process has been found to be particularly suitable for the immobilization of enzymes in anisotropic hollow fibers that exhibited no detectable enzyme leakage upon perfusion. The pH profiles measured with the enzyme in free solution and in the embedded form were similar. Kinetic parameters of multitubular enzyme reactors were investigated by measuring the rate of hydrolysis of glutamate from folic acid or methotrexate at different flow rates and substrate concentrations. The relatively slow mass transfer in such reactors was found to affect strongly the observed kinetics. The results of in vitro experiments with 5000 fiber reactors suggest that hollow fiber cartridges prepared with such membranes have clinical potential for the extracorporeal removal of methotrexate from blood.

Carboxypeptidases↗

Purification of acetate kinase by affinity chromatography.

A one-step procedure using affinity chromatography has been shown to purify to apparent homogeneity acetate kinase from a commercially available preparation and to partially purify the enzyme from a crude, cell-free extract. Since the gel's capacity for enzyme adsorption is controlled by the thermodynamics of ligand-enzyme interaction, maximization of the adsorption isotherm was attempted. Enzyme adsorption decreased logarithmically with increasing ionic strength but increased with increasing concentration of MgCl2. These competing effects caused the net adsorption of enzyme to increase to a maximum and then to decrease as the MgCl2 concentration was raised. The results allow a significant improvement in affinity column performance and have important implications for scale-up procedures.

Acetate Kinase↗

Filtration plasmapheresis in vivo.

A continuous-flow filtration plasmapheresis system has been developed as an alternative to conventional techniques for conducting plasmapheresis from blood donors. The system was tested in two stages, nonreinfusion and continuous reinfusion. Donor safety, separation efficiency, and plasma quality were examined. These studies indicate that membrane plasmapheresis is feasible, safe to the donor, and yields sufficient plasma for either therapeutic or component therapy use.

Adult↗

Evaluation of the hybrid artificial pancreas in diabetic dogs.

Immunoisolation of nonsyngeneic tissue using a selectively permeable membrane is designed to facilitate transplantation without the use of immunosuppression. The authors' studies have evaluated a hybrid artificial pancreas device that is implanted as an arteriovenous vascular shunt. Devices containing allogeneic or xenogeneic islets were implanted in diabetic dogs who had undergone pancreatectomies, and the devices eliminated the requirement for exogenous insulin for control of fasting glycemia in 11 animals for periods ranging from 1 to 8 months. Furthermore, unseeded devices in normal dogs have been shown to remain patent for over 2 years with low doses of aspirin as the only anticoagulant. These results indicate that this approach has potential as a therapy for diabetes.

Animals↗