Wire-length resonant coils, which are based on equating a wavelength of RF with the wire length u... more Wire-length resonant coils, which are based on equating a wavelength of RF with the wire length used in winding a coil, were previously developed for use in hyperthermia treatment for cancer therapy. Design modifications, coupled with a series of experiments, established their potential use for rapidly and uniformly rewarming canines following hypothermic cardiac surgery. The authors detail a new design which incorporates a single-end coaxial input and RF shielding, allowing it to be used outside of a screen room environment. Data from early experiments to investigate this system's usefulness in rewarming cryogenically preserved donor organs are presented and discussed.>
Magnetic resonance imaging was used to detect signs of regeneration of the thymus after approxima... more Magnetic resonance imaging was used to detect signs of regeneration of the thymus after approximately one month of human growth hormone administration. A 46-year-old human volunteer was placed on a regimen of recombinant human growth hormone and pharmaceutical grade dehydroepiandrosterone for one month. Mediastinal magnetic resonance images were collected at baseline and after the study period. Thymic cross sections were analyzed for total area and for the total gray area, which was taken to represent functional mass. Baseline and post-treatment blood samples were taken to follow changes in IGF-1 levels and related metabolites. The setting was an informal, non-institutional trial supervised by a physician will full informed consent of the volunteer. Visual inspection and image analysis demonstrated limited but distinct enlargement of the thymus after treatment, and an increase in the percent of thymic cross section represented by gray-appearing (functional) mass. Estimated total thymic functional volume was within the normal range at baseline, but after treatment was more than three standard deviations above the expected mean for a subject of this age, thus meeting a proposed definition of thymic hyperplasia for individuals. IGF-1 levels were confined to the upper range of normal for young adults. The present observations apparently provide the first demonstration of growth hormone induced partial reversal of established thymic involution in a normal human subject, and are consistent with previous measurements of restored immune function after the administration of human growth hormone to elderly individuals.
Cryopreservation of solid organs might be possible using a mixture of cell-permeable agents, cryo... more Cryopreservation of solid organs might be possible using a mixture of cell-permeable agents, cryoprotectants (CPA), which are designed to completely preclude ice crystal formation during cooling to cryogenic temperatures. The effects of a specific prototype solution (VS4) were evaluated by normothermic blood perfusion in vitro. Rabbit kidneys were divided into three groups: untreated controls (n=7), Euro-Collins (EC)-perfused controls (n=6) and VS4 (49%, w/v) CPA-perfused kidneys (n=7). After a 2-h blood perfusion, five of the seven CPA-perfused kidneys developed polyuria (0.21 ml×min–1×g–1) relative to untreated controls (0.07 ml×min–1×g–1) or EC-perfused kidneys (0.06 ml×min–1×g–1), owing to the lower reabsorption of water (34.3%), Na+ (34.2%) and glucose (35.6%). Furthermore, two kidneys were non-functional with virtually no urine production. Reduced tubular function was associated with reduced oxygen consumption (3.6 versus 2.3 versus 2.0 μmole×min–1×g–1 for controls, EC- and CPA-perfused kidneys, respectively) and increased weight gain (17% versus 20% versus 30%, respectively) after blood perfusion. Therefore, the current results provide insight into both the physiological effects of VS4 and the limits of reversibility of renal pathophysiological states. Our results also indicate that in vitro monitoring of oxygen consumption and weight gain of perfused organs could be used as predictors of renal function.
Donor Schwann cells, perineurial cells, and vasculature are known to survive in grafts of periphe... more Donor Schwann cells, perineurial cells, and vasculature are known to survive in grafts of peripheral nerve. In the present study, we attempted to cryopreserve nerve to determine whether these cellular components of nerve would survive after transplantation and support host axonal regeneration through the graft. Four-centimeter lengths of peroneal nerves were removed from inbred adult American Cancer Institute (ACI) rats and placed into vials that contained a cryoprotective mixture of dimethyl sulfoxide and formamide (DF) at room temperature. Each vial with nerves in DF was cooled at a rate of 1–1.5°C/minute down to –40°C at which point the vials were plunged into liquid nitrogen at –196°C. After 5 weeks of storage, the nerves were thawed and DF removed. Some of the cryopreserved-thawed ACI nerves were transplanted as isografts into the legs of ACI rats. Other ACI nerves were used as allografts and inserted into immunologically normal Fischer (FR) rats that were untreated or were immunosuppressed with the drug Cyclosporin A (Cy-A). At surgery, only one end of the nerve graft was joined to the cut proximal end of the peroneal nerve of the host. The cellular elements of ACI grafts were present at 5 weeks in grafts removed from ACI rats and FR rats treated with Cy-A. Non-immunosuppressed FR rats rejected ACI nerves as did FR rats in whom Cy-A was stopped after 5 weeks of treatment. All surviving ACI grafts underwent Wallerian degeneration and consisted of columns of Schwann cells, which in their proximal portion were associated with regenerating host axons. The donor perineurial sheath and vasculature were also present in surviving grafts. ACI isografts only were examined 20 weeks postoperatively. All normal tissue components survived in these older grafts and contained regenerated and myelinated host axons throughout their 4 cm lengths. These results demonstrated that the cellular elements of nerve can be cryopreserved, and after transplantation, survive and function. Because nerves survived after prolonged cryopreservation, it seems feasible to establish a nerve bank from which grafts can be withdrawn to repair gaps in injured nerves. However, cryopreserved nerves used as allografts remain immunogenic and require immunosuppression for their survival. Published in 1993 by Wiley-Liss, Inc.
In contemplating the future of aging, it is helpful to recognize that aging postponement, arrest,... more In contemplating the future of aging, it is helpful to recognize that aging postponement, arrest, prevention, and reversal are commonplace but still under-appreciated natural and experimental phenomena. Aging is apparently completely preventable for prolonged periods in many whole animals by nutritional cues that are not confined to calorie restriction. Aging can be substantially postponed by interfering with active life-shortening processes that are triggered by sexual maturation and reproduction in most species, perhaps including humans, but, contrary to the idea that active life shortening is necessitated by a tradeoff against reproduction, aging can also be dramatically postponed by sexual maturation and reproduction (“negative reproductive costs”) in many species, including mammals. Many fundamental age-related changes are actually reversible in adults or adult systems by the application of simple physiological interventions (“segmental aging reversal”). These reversible elemental aspects of aging include, for example, reduced transcription, reduced translation, altered gene expression, reduced DNA repair, reduced mitochondrial function, reduced regenerative capacity, replicative senescence, lipofuscin accumulation, reduced immune function, thymic involution, loss of reproductive cycling in females, age-related organ atrophy, and hair graying and balding. In addition, many aging phenotypes appear to be interlinked, such that correction of one or a few central aging pathways leads to the correction of multiple downstream pathways without the need for specific intervention in any of these dependent pathways. Collectively, such observations reveal aging on multiple levels and in diverse phyla to be driven by biological mechanisms that are considerably more accessible than is classically expected. This body of observations implies that the future of human aging can be substantially different than its past and supports recent excitement over the possibilities of human intervention.
Wire-length resonant coils, which are based on equating a wavelength of RF with the wire length u... more Wire-length resonant coils, which are based on equating a wavelength of RF with the wire length used in winding a coil, were previously developed for use in hyperthermia treatment for cancer therapy. Design modifications, coupled with a series of experiments, established their potential use for rapidly and uniformly rewarming canines following hypothermic cardiac surgery. The authors detail a new design which incorporates a single-end coaxial input and RF shielding, allowing it to be used outside of a screen room environment. Data from early experiments to investigate this system's usefulness in rewarming cryogenically preserved donor organs are presented and discussed.>
Magnetic resonance imaging was used to detect signs of regeneration of the thymus after approxima... more Magnetic resonance imaging was used to detect signs of regeneration of the thymus after approximately one month of human growth hormone administration. A 46-year-old human volunteer was placed on a regimen of recombinant human growth hormone and pharmaceutical grade dehydroepiandrosterone for one month. Mediastinal magnetic resonance images were collected at baseline and after the study period. Thymic cross sections were analyzed for total area and for the total gray area, which was taken to represent functional mass. Baseline and post-treatment blood samples were taken to follow changes in IGF-1 levels and related metabolites. The setting was an informal, non-institutional trial supervised by a physician will full informed consent of the volunteer. Visual inspection and image analysis demonstrated limited but distinct enlargement of the thymus after treatment, and an increase in the percent of thymic cross section represented by gray-appearing (functional) mass. Estimated total thymic functional volume was within the normal range at baseline, but after treatment was more than three standard deviations above the expected mean for a subject of this age, thus meeting a proposed definition of thymic hyperplasia for individuals. IGF-1 levels were confined to the upper range of normal for young adults. The present observations apparently provide the first demonstration of growth hormone induced partial reversal of established thymic involution in a normal human subject, and are consistent with previous measurements of restored immune function after the administration of human growth hormone to elderly individuals.
Cryopreservation of solid organs might be possible using a mixture of cell-permeable agents, cryo... more Cryopreservation of solid organs might be possible using a mixture of cell-permeable agents, cryoprotectants (CPA), which are designed to completely preclude ice crystal formation during cooling to cryogenic temperatures. The effects of a specific prototype solution (VS4) were evaluated by normothermic blood perfusion in vitro. Rabbit kidneys were divided into three groups: untreated controls (n=7), Euro-Collins (EC)-perfused controls (n=6) and VS4 (49%, w/v) CPA-perfused kidneys (n=7). After a 2-h blood perfusion, five of the seven CPA-perfused kidneys developed polyuria (0.21 ml×min–1×g–1) relative to untreated controls (0.07 ml×min–1×g–1) or EC-perfused kidneys (0.06 ml×min–1×g–1), owing to the lower reabsorption of water (34.3%), Na+ (34.2%) and glucose (35.6%). Furthermore, two kidneys were non-functional with virtually no urine production. Reduced tubular function was associated with reduced oxygen consumption (3.6 versus 2.3 versus 2.0 μmole×min–1×g–1 for controls, EC- and CPA-perfused kidneys, respectively) and increased weight gain (17% versus 20% versus 30%, respectively) after blood perfusion. Therefore, the current results provide insight into both the physiological effects of VS4 and the limits of reversibility of renal pathophysiological states. Our results also indicate that in vitro monitoring of oxygen consumption and weight gain of perfused organs could be used as predictors of renal function.
Donor Schwann cells, perineurial cells, and vasculature are known to survive in grafts of periphe... more Donor Schwann cells, perineurial cells, and vasculature are known to survive in grafts of peripheral nerve. In the present study, we attempted to cryopreserve nerve to determine whether these cellular components of nerve would survive after transplantation and support host axonal regeneration through the graft. Four-centimeter lengths of peroneal nerves were removed from inbred adult American Cancer Institute (ACI) rats and placed into vials that contained a cryoprotective mixture of dimethyl sulfoxide and formamide (DF) at room temperature. Each vial with nerves in DF was cooled at a rate of 1–1.5°C/minute down to –40°C at which point the vials were plunged into liquid nitrogen at –196°C. After 5 weeks of storage, the nerves were thawed and DF removed. Some of the cryopreserved-thawed ACI nerves were transplanted as isografts into the legs of ACI rats. Other ACI nerves were used as allografts and inserted into immunologically normal Fischer (FR) rats that were untreated or were immunosuppressed with the drug Cyclosporin A (Cy-A). At surgery, only one end of the nerve graft was joined to the cut proximal end of the peroneal nerve of the host. The cellular elements of ACI grafts were present at 5 weeks in grafts removed from ACI rats and FR rats treated with Cy-A. Non-immunosuppressed FR rats rejected ACI nerves as did FR rats in whom Cy-A was stopped after 5 weeks of treatment. All surviving ACI grafts underwent Wallerian degeneration and consisted of columns of Schwann cells, which in their proximal portion were associated with regenerating host axons. The donor perineurial sheath and vasculature were also present in surviving grafts. ACI isografts only were examined 20 weeks postoperatively. All normal tissue components survived in these older grafts and contained regenerated and myelinated host axons throughout their 4 cm lengths. These results demonstrated that the cellular elements of nerve can be cryopreserved, and after transplantation, survive and function. Because nerves survived after prolonged cryopreservation, it seems feasible to establish a nerve bank from which grafts can be withdrawn to repair gaps in injured nerves. However, cryopreserved nerves used as allografts remain immunogenic and require immunosuppression for their survival. Published in 1993 by Wiley-Liss, Inc.
In contemplating the future of aging, it is helpful to recognize that aging postponement, arrest,... more In contemplating the future of aging, it is helpful to recognize that aging postponement, arrest, prevention, and reversal are commonplace but still under-appreciated natural and experimental phenomena. Aging is apparently completely preventable for prolonged periods in many whole animals by nutritional cues that are not confined to calorie restriction. Aging can be substantially postponed by interfering with active life-shortening processes that are triggered by sexual maturation and reproduction in most species, perhaps including humans, but, contrary to the idea that active life shortening is necessitated by a tradeoff against reproduction, aging can also be dramatically postponed by sexual maturation and reproduction (“negative reproductive costs”) in many species, including mammals. Many fundamental age-related changes are actually reversible in adults or adult systems by the application of simple physiological interventions (“segmental aging reversal”). These reversible elemental aspects of aging include, for example, reduced transcription, reduced translation, altered gene expression, reduced DNA repair, reduced mitochondrial function, reduced regenerative capacity, replicative senescence, lipofuscin accumulation, reduced immune function, thymic involution, loss of reproductive cycling in females, age-related organ atrophy, and hair graying and balding. In addition, many aging phenotypes appear to be interlinked, such that correction of one or a few central aging pathways leads to the correction of multiple downstream pathways without the need for specific intervention in any of these dependent pathways. Collectively, such observations reveal aging on multiple levels and in diverse phyla to be driven by biological mechanisms that are considerably more accessible than is classically expected. This body of observations implies that the future of human aging can be substantially different than its past and supports recent excitement over the possibilities of human intervention.
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Papers by Gregory Fahy