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Biomedical subjects

P Terasaki

Publications and source records attributed to P Terasaki.

At least 19 recordsLinked to original sources
PubMed1992

OKT3 treatment of steroid-resistant rejection in pediatric liver transplant recipients.

Of a total of 187 consecutive liver grafts in 149 pediatric recipients, 59 episodes of steroid-resistant, biopsy-proven rejection (32% of grafts) were treated with OKT3 monoclonal antibody. After 59 OKT3-treated episodes, liver function at the end of treatment was normal in 40%, improved in 35%, and unchanged in 24%. Of 21 partial responses, 12 episodes eventually resolved to yield an overall complete response rate of 59%. CD3-positive T-cells greater than 5% occurred during 61% of OKT3-treated rejection episodes and was associated with impaired efficacy of OKT3 (30% complete response rate). Six grafts were re-treated with OKT3 for rejection and in all CD3-positive T-cells could not be maintained less than 5%. Of the six grafts requiring repeat OKT3, five failed-retreatment and required retransplantation. OKT3 antibodies of low titer were found prior to a second use of OKT3 in 65% of episodes. Patients treated with OKT3 after failing more than two preceding steroid courses had a significantly increased chance of graft loss (57%; p = 0.01). We conclude that this group of pediatric patients appeared less responsive to OKT3 compared to other series combining pediatric and adult recipients, possibly due to a more vigorous immune response in the child.

Antibodies↗
PubMed1991

International Cell Exchange, 1991.

1. During 1991, lymphocytes from 40 individuals of various races and 20 cultured B-cell lines were sent to 290 laboratories (listed in appendix) for typing. The results of the blind tests were analyzed and reported monthly. This is a summary of the year's 10 monthly exchanges. 2. Ten A-locus antigens showed 95% or greater agreement among laboratories, and 100% agreement was achieved for A2 and A3. Agreement of 95% or more was reached for 7 B-locus specificities. Both Bw54 and Bw73 showed marked improvement in detection during the last 3 years. 3. Six laboratories did not miss the assignment of any A- or B-locus antigens. The false-positive and false-negative assignment rates are given for the A- and B-loci. 4. The following variants were studied: B5-53 variants from various races, BN21, B7x40 (DT), and B7x27. 5. Aw66 assignment was found to be discrepant between the United States and European laboratories. 6. The A28 splits, Aw68 and Aw69, were studied, as were cells with different Aw68 splits. 7. Cell lines were typed by 150 laboratories, including 19 DNA laboratories. Six Class II antigens had 95% or higher detection levels, and 5 others had higher than 90% detection levels. 8. Both DNA and serology laboratories had difficulty in assigning the DRw6 splits, DRw13 and DRw14. The definition of the splits of DR3, DQw1, and DQw3 was clarified with the additional DNA typing results. 9. Amino acid sequencing confirmed a new variant of Bw53, as indicated by the assignments based on serology.

Amino Acid Sequence↗
PubMed1990

Utilization of anti-acinar cell monoclonal antibodies in the purification of rat and canine islets.

We have developed two immunological methods of islet purification using anti-acinar cell monoclonal antibodies (McAb). Pancreatic digestion with collagenase followed by depletion of acinar cells with McAb and complement or magnetic immunomicrospheres (MIMS) yields large numbers of intact islets. We compared the islets thus obtained with either handpicked (HP) islets, or islets separated on density gradients alone, for yield, purity, in vitro in sulin secretory capacities, and in vivo functional viability. Exposure of canine acinar tissue to the cytotoxic McAb resulted in a seven-fold enrichment in islet concentration, with preparations of 65% to 87% purity. Islet yield, however, was impaired by the procedure of McAb treatment, reducing the average yield from the control digestate of 40,000 to 60,000 islets/pancreas by 40% to 45%. Using the MIMS method in the rat model, the islet yield was 73% that obtained by the HP method (378 +/- 8 vs 519 +/- 31 per pancreas). The purity of the MIMS isolated islets was 84 +/- 1.9%, ranging from 75% to 95%. Analysis of the complement and MIMS treatments by in vitro static glucose tests and the capacity to restore normoglycemia after isografting in streptozotocin-induced diabetic rats indicates that the functional integrity of the islets was not affected by the purification process.

Animals↗
PubMed1990

HLA peptide matching.

With the aid of computers, the HLA molecule for 52 specificities was cut up into peptides of 2-7 amino acids in length. From all possible peptides identified, we produced an extensive table of peptides unique to each HLA specificity. The HLA types of donors and recipients of first cadaver donor transplants were then converted to their peptides and used for matching. When compared to conventional matching, tripeptide matching was more effective in identifying patients with extremely poor outcomes. The total effectiveness of peptide matching was rather modest, although it is anticipated that this new tool, together with refined knowledge of the most immunogenic peptides, will provide a more practical method of HLA matching for allotransplantation.

Amino Acid Sequence↗
PubMed1989

Fifteen-year overview of the International Cell Exchange.

1. Through the International Cell Exchange, 4 cells were shipped for blind typing to tissue typing laboratories on a monthly basis for the past 15 years. As many as 288 laboratories worldwide currently participate in this exercise. 2. The frequency of detection of a total of 85 HLA-A,B,C specificities by the laboratories has been determined. Each specificity has been classified as to the reliability of identification. 3. Lymphocytes from 27 donors were sent for retesting in as long as a 13-year interval. This provided an accurate picture of the advances in percent detection by the laboratories. 4. At least 5 variants were found by shipping cells to the laboratories: variants of A9, B21, B5, Bw52, and B40. 5. B cell lines were sent to investigate the HLA-DR antigens. At least 11 specificities had a concordance rate higher than 80% and 5 had a rate of more than 95%. 6. HLA-A,B antibodies sent for antibody characterization were classified by a new mass program for the likely epitope against which the sera were directed. As many as 28 different epitopes were detected by the sera sent in the serum exchange.

HLA Antigens↗
PubMed1989

Long-term survival of kidney grafts.

1. In the long-term period, the half-life effectively measured loss rate. For HLA-identical sib donors the half-life was 25 years; for parental donors, 13 years; and for cadaver donors, 8 years (now possibly 11 years). 2. HLA-A,B,DR matching exerted the greatest effect on half-life, for a half-life of 17 years was achieved for cadaver donors. This rate was not quite as high as that for A,B,DR matched siblings but was higher than the one haplotype mismatched parental donor transplants. 3. Caucasian recipients had a half-life of 8 years compared to 5 years for black recipients. 4. Excellent centers had a 10-year half-life compared to 5 years for fair centers. 5. Cold ischemia time over 24 hours, recipient age over 55, and donor age of 50-60 had a small effect on the half-life in the order of 1 to 3 years. 6. Among the short-term factors that affect the 1-year graft survival, there was a 12% difference between excellent and fair centers. An 11% difference between A,B,DR matched transplants and 6 A,B,DR mismatched grafts was noted. First-cadaver donor grafts had a 10% higher graft survival at 1-year than second grafts. Other factors together with the difference in 1-year graft survival between the extremes were as follows: sensitization 9%, race 8%, transfusion 6%, donor age 6%, diabetic 3%, recipient age 3% and cold ischemia 1%. Thus more factors affect short-term survival than long-term survival.

Cohort Studies↗
PubMed1988

Characterization of monoclonal antibodies CBL3 and TT62 with differing antigenic determinants specific for isolated human islets.

Identification, separation and purification of human islets from acinar cells following collagenase digestion of the pancreas remains a difficult problem. We have identified and characterized two monoclonal antibodies, CBL3 and TT62, with specific binding activity to human islets but not acinar cells. The antigens these monoclonal antibodies recognize are lipid in nature and thus unaffected by collagenase digestion of the human pancreas. These properties allow isolated human islets to be identified by fluorescein isothiocyanate-labeled CBL3 and TT62, making these monoclonal antibodies potentially useful reagents in islet identification and purification.

Animals↗
PubMed1987

Multivariate analysis of risk factors impacting on immediate and eventual cadaver allograft survival in cyclosporine-treated recipients.

A multivariate analysis dissected the impact of donor procurement variables, immunologic risk factors, and alternate cyclosporine and prednisone induction immunosuppressive regimens on the early and eventual function of 303 consecutive cadaveric renal allografts. Primarily warm, but to a slight extent cold, ischemia time had an adverse impact on allograft function, as did the requirement for vasopressor or diuretic therapy. The occurrence of initial graft non-function adversely affected the probability of three-month graft survival, but did not alter either the longevity of organs, which subsequently recovered function, or patient mortality rate. The major immunologic risk factor was a second or multiple transplant, which was associated with an increased incidence of early graft failure, and impaired renal function in successful transplants. Correlations with HLA-B and DR matching were reflected in the quality of renal function, but not in graft survival rates. Cyclosporine (CsA) administration by continuous intravenous infusion, in order to avert initial elevated mean three-day, serum radioimmunoassay drug levels reduced the incidence of initial graft non-function. High levels were also associated with impaired early and eventual renal function. Rapid posttransplant taper of corticosteroids to 30 mg prednisone by day six was associated with a greater incidence of rejection episodes and early graft failure than a taper that achieved 30 mg prednisone at 60 days. Both the serum creatinine value and the degree of hypertension observed at one month afforded good prognostic indices of eventual graft survival. Therefore, renal allografts in CsA-treated patients were sensitive not only to adverse donor and immunologic risk factors, but also to excessive CsA drug levels in the early postoperative period. These findings suggest an induction immunosuppressive strategy utilizing slightly higher initial doses of steroids for CsA-sparing during the first three days, followed by increased, but judicious, administration of CsA to achieve steroid-sparing by virtue of effective rejection prophylaxis.

Cyclosporins↗
PubMed1985

Effect of donor-specific transfusions on renal transplantation in children.

Most family members who are evaluated as kidney donors for children have high reactivity in a mixed lymphocyte culture test and are thus excluded from donation. Fifty children, most of whom had highly reactive mixed lymphocyte cultures with their donors, were challenged with three blood transfusions from their donors before transplantation and were tested for the development of lymphocytotoxic antibodies. Ten children (20%) became sensitized and had a positive T-cell or B-cell crossmatch. Sensitization occurred less frequently in children treated with azathioprine during donor-specific transfusions (11%) than in those not treated (26%), but the difference was not significant. Thirty-seven children received renal transplants from their blood donors after the donor-specific transfusions. There were no deaths, and only two patients had kidney failure. Actuarial kidney survival was 93% after 6 years. The use of donor-specific transfusion has increased the number of related-donor transplants performed and the results have been highly successful.

Actuarial Analysis↗
PubMed1985

Bone marrow from cadaver donors for transplantation.

To determine the feasibility of obtaining bone marrow cells from cadaver donors for transplantation, marrow cells were prepared from 17 cadaver donors. After surgical removal of the iliac crest, as many as 2 X 10(9) cells were isolated. Cadaver marrow had a lower percentage of T cells (mean of 10%) than did marrow from living donors. The T cells were lysed by a monoclonal antibody and human complement to a point at which no sheep red blood cell-rosetting cells were detected. Low levels of T colonies, however, grew out from the monoclonal antibody-treated cells. Although cell loss inevitably occurs from purification, antibody treatment, freezing, and thawing, sufficient numbers can be recovered for transplantation. The yield of stem cells was 84% for CFU-C, 39% for CFU-E, 81% for BFU-E, and 48% for CFU-GEMM. We suggest that T cell-depleted marrow cells from cadaver donors could be used for transplantation. Improved immunosuppressive therapy may be required, however, to prevent graft rejection of allogeneic marrow that may have minor histocompatibility differences.

Adolescent↗
PubMed1979

Autotransplantation after in vitro immunotherapy of lymphoblastic leukemia.

We have used in vitro immunotherapy before autologous bone marrow transplantation for three patients with acute lymphoblastic leukemia (ALL). Bone marrow was removed during remission, and mononuclear cells were separated by density-step centrifugation on Ficoll-Hypaque. The cells from each patient were treated with a heteroantiserum and complement to eliminate leukemic cells and were cryopreserved. Following chemotherapy and total body irradiation, the treated marrows were thawed and infused. All the patients showed positive evidence of returning marrow function before death. One patient who survived 4 months showed no evidence of leukemia at post mortem, and marrow sections demonstrated active hematopoiesis of all cell lines.

Bone Marrow Transplantation↗