Immune responses to dialyzer contents by dialysis patients.

Serum antibodies to the contents of cuprophan hollow-fiber dialyzers were demonstrated by immunodiffusion in 36 of 68 hemodialysis patients. The antibodies were not absorbed by ethylene oxide or washed cuprophan hollow fibers. No cross-reactivity with Escherichia coli lipopolysaccharide and pneumococcal polysaccharides was noted.

Immunological consequence of renal transplantation and immunosuppression. I. Alterations in human natural killer-cell activity.

The role and activity of natural killer (NK) cells following renal transplantation remain unknown. To monitor NK activity, a 51Cr release of K-562 targets in prednisone- and azathioprine-treated patients receiving renal allografts was utilized. In 18 patients in whom NK activity was measured prior to and after transplantation, a significant diminution in NK activity within 3 weeks following transplantation was demonstrated compared to pretransplant values (34.

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.

Scintigraphic evaluation of the viability of cold-preserved kidneys before transplantation.

Renal microcirculation studies utilizing microspheres can provide a highly reliable index of the viability of preserved kidneys. We describe a noninvasive method that permits subsequent transplantation of each tested kidney. Fresh canine kidneys were removed and perfused with either Collins' solution or Collins' solution with 5 mg/l of trifluoperazine (TFP), and preserved at 4 degrees to 6 degrees C in their respective perfusates for 5, 24, 48, or 72 hr.

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.

The role of calmodulin in the regulation of human lymphocyte activation.

Calmodulin (Cam) was isolated from normal and from transformed human lymphocytes by affinity chromatography on CAPP-Sepharose 4B, followed by chromatofocusing. In the presence of Ca2+, lymphocyte Cam migrated as a single protein on 2-DE, and was located on the same position as Cam extracted from dog brain and rat testis; its MW was 17,500, with a pI of 3.9.

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.

Appearance of cytoskeletal components on the surface of leukemia cells and of lymphocytes transformed by mitogens and Epstein-Barr virus.

Lactoperoxidase iodination and two-dimensional electrophoresis of the labeled proteins have demonstrated well-characterized cytoskeletal proteins (actin and tubulins) on the surface of human lymphocytes undergoing blastogenic transformation and of certain malignant human cells. Such proteins could not be detected on the surface of normal resting human lymphocytes. The most prominent cytoskeletal protein identified on the surface membrane of mitogen-transformed T and B lymphocytes was actin.

The major histocompatibility complex (HLA) as a genetic marker in human craniofacial anomalies.

Study of the incidence and segregation of the serologically detectable A and B products of the HLA complex in 140 family units in which one or more offspring was afflicted with a developmental craniofacial anomaly has uncovered no evidence of an association between HLA-A or B antigens or haplotypes and the malformations under study. Further analysis of HLA-D products in the same family units by the mixed leukocyte culture (MLC) technique has, however, uncovered a relatively high incidence of non-reactivity between the cells of one (or both) parent(s) and cells of some offspring in 41 of the 140 families included in this study. The parent couples involved in this finding were unrelated and generally did not share any HLA-SD haplotypes.

Induction of unresponsiveness to major transplantable organs in adult mammals: a recapitulation of ontogeny by irradiation and bone marrow replacement.

Transplantation of renal allografts obtained from prospectively selected genotypically DLA-identical donors into supralethally irradiated dogs reconstituted with their own stored bone marrow has produced a state of unresponsiveness to these kidneys in the recipients. Eleven of 18 kidneys transplanted at 12 hours after marrow replacement currently survive with normal function and maintain life in the recipients for 757, 800, 825, 978, 1062, 1092, 1136, 1282, 1373, 1380, and 1381 days, respectively. Similar results occurred in eight of 13 allografts transplanted at 28 hours after marrow replacement, which currently survive for 349, 363, 377, 407,436,470, 485, and 513 days, respectively, and in eight of 13 kidneys grafted at 36 hours after marrow replacement, which are surviving for 197, 247, 298, 324, 337, 396, 443, and 472 days, respectively.