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Biomedical subjects

F T Rapaport

Publications and source records attributed to F T Rapaport.

At least 127 records · Page 7Linked to original sources

Immunological monitoring in patients with end-stage renal disease.

Parameters of cell-mediated immune function were determined in 76 patients with end-stage renal disease. Lymphocyte subpopulations (OKT3, OKT4, OKT8, OKIa1, OKM1, OKT9, OKT10), natural killer (NK)-cell activity (percentage 51Cr release from K562 targets), and delayed cutaneous hypersensitivity were measured and correlated with other variables. The results indicate that (1) uremic patients have a significant diminution in the OKT4-lymphocyte subpopulation and OKT4/OKT8 (helper/suppressor) ratio compared to normal controls; (2 blood transfusions do not induce significant alterations in the helper/suppressor-cell ratio; (3) uremic patients have a significant increase in OKM1 cells compared to normal controls; (4) the majority of uremic patients in this series developed delayed cutaneous hypersensitivity responses to recall antigens and could be de novo sensitized to 2,4-dinitrochlorobenzene (DNCB); (5) skin-test reactivity could not be correlated with total circulating T cells or levels of any lymphocyte subpopulations; and (6) NK-cell activity in uremic patients is not significantly different from that in normal controls. These results highlight the varying levels and function of different lymphocyte subsets in patients with end-stage renal disease when they are treated with chronic maintenance hemodialysis.

Adult↗

Facilitation of skin allograft survival by blood leucocyte extracts. A possible mechanism for the beneficial effects of blood transfusion in human transplantation.

Fresh and frozen-stored mitochondrial, microsomal, and endoplasmic reticulum extracts of blood leucocytes act as potent alloantigens in human recipients. Similar results were obtained with freshly prepared extracts consisting of mixtures of all cytoplasmic fractions; storage of such mixtures at--20 C, followed by 1-2 hr thawing at 37 C abrogated their capacity to induce allograft sensitivity in 45 of 47 recipients. Donor-specific skin allografts and grafts from other sources exhibited significant attenuations in the tempo and intensity of rejection, ranging from first-set rejection to chronic rejection and/or to prolongations in allograft survival. In contrast with the 66.2% rejection rate of first-set skin grafts at 10 days in 71 normal subjects, only 29% of skin grafts from the leucocyte donor applied to 24 recipients of 0.1 to 9 Transplantation Antigen (T.A.) units of pooled cytoplasmic mixtures were rejected by that time. Only 17.4% similar grafts in 23 recipients of 25 to 515 T.A. units were rejected at 10 days. Seventeen skin grafts placed on recipients of 45 to 140 T.A. units of the same cytoplasmic preparation exhibited a slow rejection characterized by progressive shrinkage and eventual disappearance, with no evidence of hemorrhagic necrosis (chronic skin graft rejection). These results support the possibility that the attenuations in allograft reactivity observed in patients with end-stage renal disease after blood transfusions may be related to the leucocyte components of such transfusions. The capacity of blood transfusions to decrease reactivity to renal allografts in uremic patients maintained on hemodialysis stands in contrast with the ability of such transfusions to sensitize normal human recipients to donor-specific skin allografts. The differential effect may be related to the immunosuppressed state(s) documented in the uremic population, and/or the use of immunosuppressive drug therapy in such patients at the time of transplantation and thereafter.

Adult↗

Enhanced resistance to the effects of hypothermic ischemia in the preserved canine kidney.

Addition of trifluoperazine (TFP), a powerful calmodulin inhibitor to Collins' flush solution has exerted a significant protective effect on the cold-preserved kidney, with successful autotransplantation of 80% of preserved kidneys (4 of 5) after 72 hr of storage. In contrast, use of Collins' solution alone resulted in successful autotransplantation of only 33% (2 of 6) of kidneys after a similar period of preservation. In an attempt to analyze the significance of this result, the microcirculation of preserved kidneys was studied with injections of technetium-labeled microspheres into the kidneys, followed by study with a noninvasive radionuclide scintiphotography (RNS) technique that does not interfere with subsequent transplantation of the kidney. Such studies demonstrate that prolonged cold preservation after flush-cooling with Collins' solution is associated with a progressive deterioration of the integrity of the microcirculation, resulting in poor flow to the renal cortex. In contrast, when TFP is added to the Collins' solution, there are uniform increases in renal cortical flow in kidneys stored for 48 and 72 hr, with preservation of the integrity of the renal microcirculation. Biological testing shows a clear-cut correlation between these observations and the capacity of the tested kidneys to sustain life after retransplantation. Further experiments suggest that the decreases observed in cortical flow in kidneys preserved in the cold for 72 hr are a consequence of cellular swelling, and not of a vasospastic response. The data support the conclusion that TFP exerts its protective effect on the basis of its membrane stabilizing capacity as a calmodulin inhibitor, and not through direct vasodilatation.

Animals↗

Genetics of natural resistance to thermal injury.

The possible influence of genetic factors in conditioning the host's natural resistance to the lethal effects of severe thermal injury has been studied in 908 rats of comparable age and weight, originating from two outbred, eight inbred, and two congenic strains of animals of defined genetic background. Each animal was exposed to a standard, full-thickness, 40% body surface area skin burn by controlled contact with a heated metal plate. The 21-day postburn mortality was 100% in 217 Fisher (F-344) and 97 ACI male and female rats. The mortality was reduced to 49-63% in an intermediate group of 84 Lewis, 98 Wistar, 48 Sprague-Dawley, 96 Wistar-Furth (WF), and 48 Osborne-Mendel (OM) male rats; 48 female OM rats had a mortality of 86% at 21 days after injury. The same injury produced a mortality in 4% in 90 Buffalo (BUF) and 22% in 41 Brown-Norwegian (BN) males, while females of the same strains exhibited a 21-day mortality of 23% and 54%, respectively. Further studies of the effects of similar injury in two congenic strains of rats derived from some of the inbred lines of animals listed above yielded a 21-day mortality of 50% in 18 BN.1B(BUF) and 20% in 15 BN.1U(WF) male rats, and 65% and 36%, respectively, in females of the same lines. These data point to the importance of genetic factors as a key determinant of host resistance or susceptibility to the effects of severe thermal injury. The segregation of responses to thermal injury in inbred rats into susceptible, intermediate, and resistant groups on the basis of strain origin indicates that such natural resistance may be a quantitative trait. One of the genetic components affecting host resistance is sex-linked. The existence of genetically controlled variations in natural resistance to trauma may be an important determinant of survival and may be a source of guidelines for the triage and clinical care of injured patients. It may also be an important selective factor in evolution.

Animals↗