John Corsetti - Academia.edu (original) (raw)

Papers by John Corsetti

Research paper thumbnail of Biologic Incorporation of Allograft Anterior Cruciate Ligament Replacements

Clinical Orthopaedics and Related Research, 1996

Soft tissue allografts allow the orthopaedic surgeon to reconstruct ligaments without having to h... more Soft tissue allografts allow the orthopaedic surgeon to reconstruct ligaments without having to harvest additional tissue from the patient, which can eliminate donor tissue site morbidity and reduce surgical time. There is still much to be learned about the biologic aspects of the remodeling and incorporation of allografts in comparison with autografts. The interaction of cells, matrix, and biomolecules, such as growth factors, plays an important role that can potentially modulate, enhance, or impede the healing response in allografts. The authors have shown that, in the short term, allografts used in anterior cruciate ligament reconstruction are not as rapidly remodeled and incorporated into host tissue as are autografts. The long-term implications of this slower allograft incorporation in anterior cruciate ligament reconstruction are still unknown. The cells that repopulate allografts and autografts favor production of smaller diameter collagen fibrils, which in sufficient numbers can provide significant strength. Use of allografts raises other issues and potential disadvantages, including scarcity, immunogenicity, the potential for disease transmission, and cost-effectiveness in anterior cruciate ligament reconstruction.

Research paper thumbnail of The biochemical pathway mediating the proliferative response of bone cells to a mechanical stimulus

Journal of Bone and Joint Surgery American Volume, Sep 1, 1996

Calvarial bone cells of rats were subjected to either a cyclic biaxial strain of 0.17 per cent (1... more Calvarial bone cells of rats were subjected to either a cyclic biaxial strain of 0.17 per cent (1700 microstrain) or a hydrostatic pressure of 2.5, five, or ten pounds per square inch (17.2,34.5, or sixty-nine kilopascals). The frequency was held constant at one hertz for both types of mechanical stimulation. When cultured bone cells that had been subjected to a cyclic biaxial strain for two hours were harvested twenty-two hours later, it was found that the level of prostaglandin E 2 had increased significantly (p < 0.01) as had cellular proliferation (p < 0.01), as indicated by the incorporation of [ 3 H] -thymidine. The addition to the medium of indomethacin, an inhibitor of prostaglandin synthesis, at a ten-micromolar concentration significantly inhibited (p < 0.01) the increase in prostaglandin E, synthesis but had no effect on the strain-induced increase in cellular proliferation, as indicated by the incorporation of [ 3 H] -thymidine. Twenty-four hours after exposure to the same cyclic biaxial strain for thirty seconds, other cultured bone cells showed a significant increase in the level of cytoskeletal calmodulin (p < 0.05) and in the DNA content (p < 0.05). N-(6aminohexyl)-5-chloro-l-naphthalene-sulfonamide (W-7), a calmodulin antagonist, was added to the medium at a one-micromolar concentration, which had been shown to have no effect on the increase in the DNA content of control cells; W-7 completely blocked the increase in the level of cytoskeletal calmodulin and in the DNA content in the cells that were subjected to a cyclic biaxial strain.

Research paper thumbnail of Hypocalcemia in experimental pancreatitis occurs independently of changes in serum nonesterified fatty acid levels

International journal of pancreatology : official journal of the International Association of Pancreatology, 1990

Hypocalcemia and lipid abnormalities commonly occur in acute pancreatitis. Experimentally, increa... more Hypocalcemia and lipid abnormalities commonly occur in acute pancreatitis. Experimentally, increased plasma concentrations of free fatty acids (NEFA) can lower the serum calcium (Ca). We hypothesized that changes in blood-ionized calcium might parallel changes in NEFA concentration in pancreatitis. This hypothesis was tested in a model of severe necrotizing pancreatitis and a model of mild edematous pancreatitis. Adult male Sprague-Dawley rats (300-400 g) were randomized to receive: 100 microL sodium glycodeoxycholic acid (GDOC 34 mmol/L) infused into the pancreatic duct to produce severe necrotizing pancreatitis (Group 1); 100 microL 0.9% NaCl (NS) infused into the pancreatic duct (Group 2); Sham laparotomy (Group 3); A 6 h IV infusion of cerulein (5 mucg/kg/h) to produce mild edematous pancreatitis (Group 4); and a 6 h IV infusion of NS (Group 5). A significant time dependent decrease in blood-ionized Ca concentration, compared to normal rats, was observed in both GDOC-pancreatiti...

Research paper thumbnail of Biochemical Pathway Mediating the Response of Bone Cells to Capacitive Coupling

Clinical Orthopaedics and Related Research, 1998

Rat calvarial bone cells or mouse MC3T3-E1 bone cells subjected to a capacitively coupled electri... more Rat calvarial bone cells or mouse MC3T3-E1 bone cells subjected to a capacitively coupled electric field of 20 mV/cm consistently showed significant increases in cellular proliferation as determined by deoxyribonucleic acid content. Verapamil, a membrane calcium channel blocker; W-7, a calmodulin antagonist; indocin, a prostaglandin synthesis inhibitor; or bromophenacyl bromide, a phospholipase A2 inhibitor, each at a concentration that did not interfere with cell proliferation in control cultures, inhibited proliferation in those cultures subjected to the electric field. In contrast, neomycin, an inhibitor of the inositol phosphate cascade, did not inhibit this electrically induced cellular proliferation. Prostaglandin E2 production also was increased significantly with electrical stimulation, and this increase was inhibited by verapamil or indocin but not by neomycin. Thus, the data suggest that the signal transduction mediating the proliferative response of cultured bone cells to a capacitively coupled field involved transmembrane calcium translocation via voltage gated calcium channels, activation of phospholipase A2, and a subsequent increase in prostaglandin E2. Increases in cytosolic calcium and activated calmodulin are implied. The inositol phosphate pathway, unlike its dominant role in signal transduction in mechanically stimulated bone cells, does not appear to play a role in signal transduction in the proliferative response of bone cells to electrical stimulation.

Research paper thumbnail of Failure of Anterior Cruciate Ligament Reconstruction

Clinical Orthopaedics and Related Research, 1996

The replacement tissue used for anterior cruciate ligament reconstruction undergoes extensive bio... more The replacement tissue used for anterior cruciate ligament reconstruction undergoes extensive biologic remodeling and incorporation after implantation. Successful biologic incorporation of the graft is dependent on a number of factors including graft placement, tensioning, and the nature of the tissue (allograft versus autograft). Failure of an anterior cruciate ligament reconstruction may occur on the basis of either technical, mechanical, or biological factors. Biologic factors include cellular repopulation, matrix remodeling, the ultimate small diameter collagen fibril orientation, the final cross sectional area of the graft, a favorable vascularization, and not overloading the graft during the remodeling process. The fully incorporated graft never duplicates the native anterior cruciate ligament but works as a check reign that makes the knee more functional.

Research paper thumbnail of Biologic Incorporation of Allograft Anterior Cruciate Ligament Replacements

Clinical Orthopaedics and Related Research, 1996

Soft tissue allografts allow the orthopaedic surgeon to reconstruct ligaments without having to h... more Soft tissue allografts allow the orthopaedic surgeon to reconstruct ligaments without having to harvest additional tissue from the patient, which can eliminate donor tissue site morbidity and reduce surgical time. There is still much to be learned about the biologic aspects of the remodeling and incorporation of allografts in comparison with autografts. The interaction of cells, matrix, and biomolecules, such as growth factors, plays an important role that can potentially modulate, enhance, or impede the healing response in allografts. The authors have shown that, in the short term, allografts used in anterior cruciate ligament reconstruction are not as rapidly remodeled and incorporated into host tissue as are autografts. The long-term implications of this slower allograft incorporation in anterior cruciate ligament reconstruction are still unknown. The cells that repopulate allografts and autografts favor production of smaller diameter collagen fibrils, which in sufficient numbers can provide significant strength. Use of allografts raises other issues and potential disadvantages, including scarcity, immunogenicity, the potential for disease transmission, and cost-effectiveness in anterior cruciate ligament reconstruction.

Research paper thumbnail of Biologic Incorporation of Allograft Anterior Cruciate Ligament Replacements

Clinical Orthopaedics and Related Research, 1996

Soft tissue allografts allow the orthopaedic surgeon to reconstruct ligaments without having to h... more Soft tissue allografts allow the orthopaedic surgeon to reconstruct ligaments without having to harvest additional tissue from the patient, which can eliminate donor tissue site morbidity and reduce surgical time. There is still much to be learned about the biologic aspects of the remodeling and incorporation of allografts in comparison with autografts. The interaction of cells, matrix, and biomolecules, such as growth factors, plays an important role that can potentially modulate, enhance, or impede the healing response in allografts. The authors have shown that, in the short term, allografts used in anterior cruciate ligament reconstruction are not as rapidly remodeled and incorporated into host tissue as are autografts. The long-term implications of this slower allograft incorporation in anterior cruciate ligament reconstruction are still unknown. The cells that repopulate allografts and autografts favor production of smaller diameter collagen fibrils, which in sufficient numbers can provide significant strength. Use of allografts raises other issues and potential disadvantages, including scarcity, immunogenicity, the potential for disease transmission, and cost-effectiveness in anterior cruciate ligament reconstruction.

Research paper thumbnail of The biochemical pathway mediating the proliferative response of bone cells to a mechanical stimulus

Journal of Bone and Joint Surgery American Volume, Sep 1, 1996

Calvarial bone cells of rats were subjected to either a cyclic biaxial strain of 0.17 per cent (1... more Calvarial bone cells of rats were subjected to either a cyclic biaxial strain of 0.17 per cent (1700 microstrain) or a hydrostatic pressure of 2.5, five, or ten pounds per square inch (17.2,34.5, or sixty-nine kilopascals). The frequency was held constant at one hertz for both types of mechanical stimulation. When cultured bone cells that had been subjected to a cyclic biaxial strain for two hours were harvested twenty-two hours later, it was found that the level of prostaglandin E 2 had increased significantly (p < 0.01) as had cellular proliferation (p < 0.01), as indicated by the incorporation of [ 3 H] -thymidine. The addition to the medium of indomethacin, an inhibitor of prostaglandin synthesis, at a ten-micromolar concentration significantly inhibited (p < 0.01) the increase in prostaglandin E, synthesis but had no effect on the strain-induced increase in cellular proliferation, as indicated by the incorporation of [ 3 H] -thymidine. Twenty-four hours after exposure to the same cyclic biaxial strain for thirty seconds, other cultured bone cells showed a significant increase in the level of cytoskeletal calmodulin (p < 0.05) and in the DNA content (p < 0.05). N-(6aminohexyl)-5-chloro-l-naphthalene-sulfonamide (W-7), a calmodulin antagonist, was added to the medium at a one-micromolar concentration, which had been shown to have no effect on the increase in the DNA content of control cells; W-7 completely blocked the increase in the level of cytoskeletal calmodulin and in the DNA content in the cells that were subjected to a cyclic biaxial strain.

Research paper thumbnail of Hypocalcemia in experimental pancreatitis occurs independently of changes in serum nonesterified fatty acid levels

International journal of pancreatology : official journal of the International Association of Pancreatology, 1990

Hypocalcemia and lipid abnormalities commonly occur in acute pancreatitis. Experimentally, increa... more Hypocalcemia and lipid abnormalities commonly occur in acute pancreatitis. Experimentally, increased plasma concentrations of free fatty acids (NEFA) can lower the serum calcium (Ca). We hypothesized that changes in blood-ionized calcium might parallel changes in NEFA concentration in pancreatitis. This hypothesis was tested in a model of severe necrotizing pancreatitis and a model of mild edematous pancreatitis. Adult male Sprague-Dawley rats (300-400 g) were randomized to receive: 100 microL sodium glycodeoxycholic acid (GDOC 34 mmol/L) infused into the pancreatic duct to produce severe necrotizing pancreatitis (Group 1); 100 microL 0.9% NaCl (NS) infused into the pancreatic duct (Group 2); Sham laparotomy (Group 3); A 6 h IV infusion of cerulein (5 mucg/kg/h) to produce mild edematous pancreatitis (Group 4); and a 6 h IV infusion of NS (Group 5). A significant time dependent decrease in blood-ionized Ca concentration, compared to normal rats, was observed in both GDOC-pancreatiti...

Research paper thumbnail of Biochemical Pathway Mediating the Response of Bone Cells to Capacitive Coupling

Clinical Orthopaedics and Related Research, 1998

Rat calvarial bone cells or mouse MC3T3-E1 bone cells subjected to a capacitively coupled electri... more Rat calvarial bone cells or mouse MC3T3-E1 bone cells subjected to a capacitively coupled electric field of 20 mV/cm consistently showed significant increases in cellular proliferation as determined by deoxyribonucleic acid content. Verapamil, a membrane calcium channel blocker; W-7, a calmodulin antagonist; indocin, a prostaglandin synthesis inhibitor; or bromophenacyl bromide, a phospholipase A2 inhibitor, each at a concentration that did not interfere with cell proliferation in control cultures, inhibited proliferation in those cultures subjected to the electric field. In contrast, neomycin, an inhibitor of the inositol phosphate cascade, did not inhibit this electrically induced cellular proliferation. Prostaglandin E2 production also was increased significantly with electrical stimulation, and this increase was inhibited by verapamil or indocin but not by neomycin. Thus, the data suggest that the signal transduction mediating the proliferative response of cultured bone cells to a capacitively coupled field involved transmembrane calcium translocation via voltage gated calcium channels, activation of phospholipase A2, and a subsequent increase in prostaglandin E2. Increases in cytosolic calcium and activated calmodulin are implied. The inositol phosphate pathway, unlike its dominant role in signal transduction in mechanically stimulated bone cells, does not appear to play a role in signal transduction in the proliferative response of bone cells to electrical stimulation.

Research paper thumbnail of Failure of Anterior Cruciate Ligament Reconstruction

Clinical Orthopaedics and Related Research, 1996

The replacement tissue used for anterior cruciate ligament reconstruction undergoes extensive bio... more The replacement tissue used for anterior cruciate ligament reconstruction undergoes extensive biologic remodeling and incorporation after implantation. Successful biologic incorporation of the graft is dependent on a number of factors including graft placement, tensioning, and the nature of the tissue (allograft versus autograft). Failure of an anterior cruciate ligament reconstruction may occur on the basis of either technical, mechanical, or biological factors. Biologic factors include cellular repopulation, matrix remodeling, the ultimate small diameter collagen fibril orientation, the final cross sectional area of the graft, a favorable vascularization, and not overloading the graft during the remodeling process. The fully incorporated graft never duplicates the native anterior cruciate ligament but works as a check reign that makes the knee more functional.

Research paper thumbnail of Biologic Incorporation of Allograft Anterior Cruciate Ligament Replacements

Clinical Orthopaedics and Related Research, 1996

Soft tissue allografts allow the orthopaedic surgeon to reconstruct ligaments without having to h... more Soft tissue allografts allow the orthopaedic surgeon to reconstruct ligaments without having to harvest additional tissue from the patient, which can eliminate donor tissue site morbidity and reduce surgical time. There is still much to be learned about the biologic aspects of the remodeling and incorporation of allografts in comparison with autografts. The interaction of cells, matrix, and biomolecules, such as growth factors, plays an important role that can potentially modulate, enhance, or impede the healing response in allografts. The authors have shown that, in the short term, allografts used in anterior cruciate ligament reconstruction are not as rapidly remodeled and incorporated into host tissue as are autografts. The long-term implications of this slower allograft incorporation in anterior cruciate ligament reconstruction are still unknown. The cells that repopulate allografts and autografts favor production of smaller diameter collagen fibrils, which in sufficient numbers can provide significant strength. Use of allografts raises other issues and potential disadvantages, including scarcity, immunogenicity, the potential for disease transmission, and cost-effectiveness in anterior cruciate ligament reconstruction.