Sandra Socarras - Academia.edu (original) (raw)
Papers by Sandra Socarras
Transplantation, 1995
Although it has long been appreciated that establishment of chimerism is important in the acquisi... more Although it has long been appreciated that establishment of chimerism is important in the acquisition and maintenance of allograft tolerance, the importance of this relationship has been reemphasized recently. Using the exquisite sensitivity of the polymerase chain reaction we have studied qualitatively and quantitatively the presence of donor-derived chimeric cells in relation to the ability of neonatally injected mice to display skin graft tolerance or rejection. We have found that virtually all mice that receive neonatal injections of F1 hematopoietic cells acquire donor-derived chimerism that is detectable in blood, spleen, lymph nodes, and thymus. Surprisingly, neither the presence nor the quantity of chimeric cells predicts whether a particular neonatally injected mouse will accept or reject donor-specific skin allografts. Moreover, whether the test skin allograft is accepted (tolerance) or rejected by neonatally injected mice, chimerism typically remains detectable within recipient lymphoid tissues. In functionally tolerant mice, challenge with a test skin allograft actually leads to a remarkable expansion in donor-derived genetic sequences, implying that donor-derived cells have been induced by the graft to undergo proliferation. Since persistence of chimerism without proliferation after test grafting is characteristic of mice that fail to display tolerance, we believe that achievement of a threshold level of donor-derived alloantigen may be necessary to retain the tolerant state. We conclude that chimerism is essential for the induction of neonatally induced tolerance, and its expansion may play an important role in the maintenance of that tolerance, when challenged by an allograft.
Journal of Pharmaceutical and Biomedical Analysis, 2009
Excursions from storage condition requirements may affect product performance and stability. The ... more Excursions from storage condition requirements may affect product performance and stability. The effects of temperature excursion on stability depend on the amount of time that a product is subjected to these conditions, temperature level, and activation energy. Both time at elevated temperature and the temperature level can be directly measured, while activation energy needs to be estimated from the accelerated stability tests. Coulter Clenz reagent degradation information is used to demonstrate the effects of temperature excursions. The stability of the product is affected by any excursion, but Coulter Clenz will not lose all of its stability for excursion of up to 30 days at 35 degrees C and 20 days at 40 degrees C. Temperature excursion for up to 20 days at 40 degrees C will reduce the stability of a product that has activation energy in the range of 26-30kcalmol(-1) approximately by 5-7 months. Products with lower activation energy will have a significantly lower reduction in stability. The effects of excursions on shelf life performance are less severe when lower level of risk is implemented to establish the claimed shelf life. The proposed model can effectively predict temperature excursion if used within the scope of a product performance and its characteristics.
European Journal of Immunology, 1991
Neonatal transplantation tolerance was one of the first experimental systems to reveal that toler... more Neonatal transplantation tolerance was one of the first experimental systems to reveal that tolerance could be achieved to non-self antigens in living animals. Functional and direct evidence (obtained by the use of monoclonal antibodies directed at T cell receptors specifically reactive with I-E molecules) confirm that tolerance is achieved, at least in part, via clonal elimination of developing thymocytes. In this report, we show that induction of tolerance of class I alloantigens in neonatal mice is governed by expression of I-E molecules. Neonatal I-E non-expressor mice proved to be highly resistant to the acquisition of class I tolerance if the donor inoculum expressed disparate class I antigens as well as I-E molecules. The spleens of the few class I-tolerant, I-E non-expressor mice that were generated were found to be depleted of I-E-reactive (RR315+) T cells, whereas no such depletion was observed in their neonatally injected, but non-tolerant littermates. By contrast we found no resistance to tolerance of I-A alloantigens when neonatal I-E non-expressor mice received injections of I-A-disparate, I-E-bearing donor cells. In these tolerant mice, splenic I-E-reactive T cells were readily detected in apparently normal amounts. These results indicate that lack of I-E expression in newborn mice confers resistance to tolerance induction to class I alloantigens, especially when the latter are expressed on donor cells that also display I-E molecules. The possible mechanisms operating to produce resistance to tolerance induction in neonatal mice are discussed, including the possibilities that (a) I-E may act as a restricting element during tolerance induction (an ontogenic process), and (b) the expression of I-E on H-2-disparate, I-E-expressing test skin allografts may provide a source of "help" for CD8+ cytotoxic T cell precursors, leading to graft rejection.
Transplant Immunology, 1993
Transplantation, 1995
Although it has long been appreciated that establishment of chimerism is important in the acquisi... more Although it has long been appreciated that establishment of chimerism is important in the acquisition and maintenance of allograft tolerance, the importance of this relationship has been reemphasized recently. Using the exquisite sensitivity of the polymerase chain reaction we have studied qualitatively and quantitatively the presence of donor-derived chimeric cells in relation to the ability of neonatally injected mice to display skin graft tolerance or rejection. We have found that virtually all mice that receive neonatal injections of F1 hematopoietic cells acquire donor-derived chimerism that is detectable in blood, spleen, lymph nodes, and thymus. Surprisingly, neither the presence nor the quantity of chimeric cells predicts whether a particular neonatally injected mouse will accept or reject donor-specific skin allografts. Moreover, whether the test skin allograft is accepted (tolerance) or rejected by neonatally injected mice, chimerism typically remains detectable within recipient lymphoid tissues. In functionally tolerant mice, challenge with a test skin allograft actually leads to a remarkable expansion in donor-derived genetic sequences, implying that donor-derived cells have been induced by the graft to undergo proliferation. Since persistence of chimerism without proliferation after test grafting is characteristic of mice that fail to display tolerance, we believe that achievement of a threshold level of donor-derived alloantigen may be necessary to retain the tolerant state. We conclude that chimerism is essential for the induction of neonatally induced tolerance, and its expansion may play an important role in the maintenance of that tolerance, when challenged by an allograft.
Journal of Pharmaceutical and Biomedical Analysis, 2009
Excursions from storage condition requirements may affect product performance and stability. The ... more Excursions from storage condition requirements may affect product performance and stability. The effects of temperature excursion on stability depend on the amount of time that a product is subjected to these conditions, temperature level, and activation energy. Both time at elevated temperature and the temperature level can be directly measured, while activation energy needs to be estimated from the accelerated stability tests. Coulter Clenz reagent degradation information is used to demonstrate the effects of temperature excursions. The stability of the product is affected by any excursion, but Coulter Clenz will not lose all of its stability for excursion of up to 30 days at 35 degrees C and 20 days at 40 degrees C. Temperature excursion for up to 20 days at 40 degrees C will reduce the stability of a product that has activation energy in the range of 26-30kcalmol(-1) approximately by 5-7 months. Products with lower activation energy will have a significantly lower reduction in stability. The effects of excursions on shelf life performance are less severe when lower level of risk is implemented to establish the claimed shelf life. The proposed model can effectively predict temperature excursion if used within the scope of a product performance and its characteristics.
European Journal of Immunology, 1991
Neonatal transplantation tolerance was one of the first experimental systems to reveal that toler... more Neonatal transplantation tolerance was one of the first experimental systems to reveal that tolerance could be achieved to non-self antigens in living animals. Functional and direct evidence (obtained by the use of monoclonal antibodies directed at T cell receptors specifically reactive with I-E molecules) confirm that tolerance is achieved, at least in part, via clonal elimination of developing thymocytes. In this report, we show that induction of tolerance of class I alloantigens in neonatal mice is governed by expression of I-E molecules. Neonatal I-E non-expressor mice proved to be highly resistant to the acquisition of class I tolerance if the donor inoculum expressed disparate class I antigens as well as I-E molecules. The spleens of the few class I-tolerant, I-E non-expressor mice that were generated were found to be depleted of I-E-reactive (RR315+) T cells, whereas no such depletion was observed in their neonatally injected, but non-tolerant littermates. By contrast we found no resistance to tolerance of I-A alloantigens when neonatal I-E non-expressor mice received injections of I-A-disparate, I-E-bearing donor cells. In these tolerant mice, splenic I-E-reactive T cells were readily detected in apparently normal amounts. These results indicate that lack of I-E expression in newborn mice confers resistance to tolerance induction to class I alloantigens, especially when the latter are expressed on donor cells that also display I-E molecules. The possible mechanisms operating to produce resistance to tolerance induction in neonatal mice are discussed, including the possibilities that (a) I-E may act as a restricting element during tolerance induction (an ontogenic process), and (b) the expression of I-E on H-2-disparate, I-E-expressing test skin allografts may provide a source of "help" for CD8+ cytotoxic T cell precursors, leading to graft rejection.
Transplant Immunology, 1993