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G A Zazanis

Publications and source records attributed to G A Zazanis.

9 recordsLinked to original sources
PubMed1997

Transplanted oligodendrocyte progenitor cells expressing a dominant-negative FGF receptor transgene fail to migrate in vivo.

The proliferation, migration, survival, and differentiation of oligodendrocyte progenitor cells, precursors to myelin-forming oligodendrocytes in the CNS, are controlled by a number of polypeptide growth factors in vitro. The requirement and roles for individual factors in vivo, however, are primarily unknown. We have used a cell transplantation approach to examine the role of fibroblast growth factor (FGF) in oligodendrocyte development in vivo. A dominant-negative version of the FGF receptor-1 transgene was introduced into oligodendrocyte progenitors in vitro, generating cells that were nonresponsive to FGF but responsive to other mitogens. When transplanted into the brains of neonatal rats, mutant cells were unable to migrate and remained within the ventricles. These results suggest a role for FGF signaling in establishing a motile phenotype for oligodendrocyte progenitor cell migration in vivo and illustrate the utility of a somatic cell mutagenesis approach for the study of gene function during CNS development in vivo.

Animals↗
PubMed1995

Motor function analysis of myelin mutant mice using a rotarod.

We have examined motor control in normal and shiverer mutant mice using the rotarod assay, a forced motor activity which tests for balance and co-ordination. Shiverer mice carry a deletion of the myelin basic protein (MBP) gene, resulting in CNS dysmyelination and characteristic motor dysfunction. Homozygous mutant mice had a significant increase in cumulative falls from the rotarod relative to heterozygous mice. Non-acclimated animals of both genotypes showed progressive improvement in performance when tested on successive days. The rotarod test also discriminated shiverer mutants from animals that received gene therapy intervention. Shiverer animals carrying an MBP transgene showed gene-dosage-dependent improvements in motor function, and mutants which received thalamic transplants of wild type oligodendrocyte precursor cells showed improvement relative to sham operated and non-transplanted controls. Thus the rotarod is a sensitive measure of motor function in hypomyelinated mice, and may be useful for assessing the results of experimental manipulations including transgenic gene therapy and cell transplantation.

Animals↗
PubMed1991

Use of collagen film as a dural substitute: preliminary animal studies.

Cadaver grafts, laminated metallic materials, and synthetic fabrics have been evaluated as dural substitutes. Use of cadaver tissues is limited by fear of transmission of infectious disease while use of synthetic materials is associated with implant encapsulation and foreign body reactions. The purpose of this study is to evaluate the use of collagen film as a dural substitute. Collagen films prepared from bovine skin were used to replace the dura of rabbits and histological observations were made at 16, 28, 42, and 56 days postimplantation. Controls consisted of dura that was removed and then reattached. Control dura showed no signs of inflammation or adhesion to underlying tissue at 16 and 28 days postimplantation. By 56 days postimplantation, extensive connective tissue deposition was observed in close proximity to adjacent bone as well as pia arachnoid adhesions. Implanted collagen film behaved in a similar manner to control dura showing minimal inflammatory response at all time periods. At 56 days postimplantation collagen film appeared strongly infiltrated by connective tissue cells that deposited new collagen. The results of this study suggest that a reconstituted type I collagen film crosslinked with cyanamide acts as a temporary barrier preventing loss of fluid and adhesion formation. It is replaced after approximately 2 months with host collagen with limited inflammatory and fibrotic complications. Further studies are needed to completely characterize the new connective tissue formed as well as long-term biocompatibility and functioning of a reconstituted collagen dural substitute.

Animals↗
PubMedDate not supplied

Prevention of postoperative adhesions with the chitin derivative N-O-carboxymethylchitosan.

The ideal barrier agent for the prevention of surgical adhesions has remained elusive. We have examined the ability of a new hydrogel N-O-carboxymethylchitosan, a derivative of chitin with properties similar to the extracellular matrix, to prevent adhesions when applied topically to traumatized mesothelial surfaces. In two rodent adhesion models (pericardial and peritoneal), the application of N-O-carboxymethylchitosan significantly prevented or minimized the formation of scar and fibrosis. According to a scoring system from 0 to 3 (0 = no adhesions and 3 = severe dense adhesions), control groups in each model consistently produced severe dense adhesions (2.9 +/- 0.2, 2.7 +/- 0.3). All treated groups consistently scored less than 1.0, indicating minimal or no fibrosis. The differences between the control and treated groups were statistically significant (p < 0.05). Thus, the application of N-O-carboxymethylchitosan to traumatized mesothelial surfaces may have significant potential in the prevention of postoperative adhesion formation.

Journal Article↗
PubMedDate not supplied

An inhibitor of cell proliferation associated with adhesion formation is suppressed by N,O-carboxymethyl chitosan.

Surgical adhesions are a major cause of morbidity and mortality. The ideal barrier agent will both minimize adhesions and provide a milieu for the regeneration of the mesothelium lining of the abdominal and thoracic cavities. N,O-Carboxymethylchitosan (NOCC), a derivation of chitin that markedly reduces adhesions, may function to modulate intracellular signals such as growth factors and cytokines in the inflammatory exudate. Since transforming growth factor-beta is implicated in the fibrotic process, we investigated the possibility that NOCC's effects on adhesion formation reflects a modulation of TGF-beta activity. Using a biological assay for inhibition of cell proliferation to detect TGF-beta activity, we demonstrate that NOCC suppresses the levels of an inhibitor of cell proliferation released into serum and peritoneal exudates after cecal abrasion in the rat. However, this activity was distinct from known forms of TGF-beta as determined using both TGF-beta-neutralizing antisera and a TGF-beta-resistant cell proliferation assay. Thus at least one potential effect of NOCC involves a mechanism distinct from TGF-beta inhibition.

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