Anti-Serum to Cultured Human Lymphoblasts

Najarían, John S.; Simmons, Richard L.; Gewürz, Henry; Moberg, A; Merkel, Frederick K.; Moore, George E.

doi:10.1097/00000658-196910000-00013

Cited by 55 publications

(5 citation statements)

References 13 publications

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“… 39 Najarian and Starzl effectively treated kidney rejection in humans with horse antihuman globulin. 40 , 41 Kaden (1992-1998) reported less ATN-DGF after induction using rATG-Fresenius. 42 The efficacy of induction with a single 9 mg/kg bolus of rATG-Fresenius versus two 20-mg doses of basiliximab was supported by Kyllonen in work reported in 2007, and SD rATG induction before weaning recipients to CNI monotherapy was reported by Starzl and Shapiro.…”

Section: Discussionmentioning

confidence: 99%

A Randomized 2×2 Factorial Trial, Part 1

et al. 2015

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Section: Discussionmentioning

confidence: 99%

A Randomized 2×2 Factorial Trial, Part 1

et al. 2015

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“…Bovine serum albumin (a test for the vehicle of ALS/ALG) was without influence on survival. Cultured human lymphoblast (Najarian et al, 1969) serum (RPMI) was without effect a t the dose used (4 mg/kg IV qd). Increasing the dose t o four t o five times above this in four other animals was without effect on first-and second-set skin grafts.…”

Section: Methodsmentioning

confidence: 99%

Biological testing of antilymphocyte sera and globulin in the baboon

Murphy

Brede

Schoonees

et al. 1971

Journal of Surgical Oncology

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A variety of antilymphocyte sera (ALS) and globulins (ALG) as well as other adjuvant compounds (procytoxide, PCO) were evaluated in 40 adult chacma baboons housed at the Roswell Park Surgical Primate Center. Animals were characterized in terms of human erythrocyte and leukocyte compatibility and then entered into the test evaluation program. Paired animals exchanged first-and second-set skin grafts and subsequently renal allografts with and without therapy. Appropriate interval periods elapsed between each allograft test period. Baboon-goat ALS and human thymus ALG were all significantly effective in prolongation of first-and second-set skin grafts as well as renal allografts. PCO slightly prolonged survival of sensitized renal allograft recipients. Serological (immunochemical) studies, level of peripheral lymphocytes, and prior in vitro tests all failed to correlate with the observed effectiveness of the ALS and ALG preparations noted in the present series of baboons. The baboon thus appears to be a vital as well as valid in viva model for testing and evaluation of ALS and ALG preparations.

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“…Polyclonal ALG was never used in more than about 15% of kidney transplant cases reported to registries up to the early 1980s, in part because it was in no sense a standardized drug such as azathioprine or prednisone. Although the use by Najarian and Simmons [176] of known numbers of cultured human lymphoblasts for accurately timed horse immunization improved the predictability of the ALG potency, batch-to-batch variations in potency remained problematic. "Antibody therapy" came of age with monoclonal antibodies, whose production was made feasible by the hybridoma technology of Kohler and Milstein [177].…”

Section: Improved Immunosuppressionmentioning

confidence: 99%

History of Clinical Transplantation

Starzl

2000

World j. surg.

153

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The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations in surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipients had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts.

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Anti-Serum to Cultured Human Lymphoblasts

Cited by 55 publications

References 13 publications

A Randomized 2×2 Factorial Trial, Part 1

A Randomized 2×2 Factorial Trial, Part 1

Biological testing of antilymphocyte sera and globulin in the baboon

History of Clinical Transplantation

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