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S Takemoto

Publications and source records attributed to S Takemoto.

At least 73 records · Page 4Linked to original sources

Six-antigen-matched transplants. Causes of failure.

The causes of failure were studied for 1386 cadaver kidney transplants shared through the UNOS 6-antigen match program from November 1987 to February 1992. The one-year graft survival for 1004 HLA-matched first cadaver transplants was 88% compared with 90% for parent donor and 78% for 22,188 HLA-mismatched first cadaveric donors reported to the UNOS Scientific Renal Transplant Registry. The cause of graft loss was immunological in 55% of HLA-mismatched cadaver kidney failures, whereas only 39% of the HLA-matched graft failures were immunological. The fraction of immunological failures in HLA-matched first transplant recipients younger than age 17 was 57% and decreased with increasing age to 14% for recipients older than age 60. Death with a functioning graft accounted for 50% of failures in the older age group. Sensitization was associated with an increased incidence of immunological failures in matched first graft recipients from 36% in nonsensitized to 53% in broadly sensitized patients, and 55% of failures were immunological in second graft recipients compared with 39% in first transplants. Some immunological failures may have been due to tissue typing, since only 18% of failures in kidneys with well-defined HLA antigens were immunological, whereas 44% of kidneys matched with more difficult HLA antigens were lost due to immunological causes. The results indicate that phenotypically identical cadaver renal transplants have a reduced rate of immunological failures. As the accuracy of this tissue typing for the more difficult HLA antigens improves, immunological failures in this group of transplants will decline even further.

Adolescent↗

Expression of fibronectin and adhesion to fibronectin in myeloma cell lines.

Fibronectin (FN) expression in six myeloma, two mature B-cell lines, and four T-cell lines was analyzed. All myeloma cell lines expressed FN at various levels, while mature B- and T-cell lines apparently had less FN. Moreover, an extramedullary plasmacytoma-derived myeloma cell line, KHM7, was found to secrete FN into the culture medium. Fibronectin receptors, VLA4 or VLA5, were expressed at various levels on all myeloma cell lines. An adhesion assay revealed three of six myeloma cell lines bound to FN. However, there was no correlation between binding to FN and FN receptor expression, indicating a complicated FN binding pathway. The mechanism and pathological significance of FN expression and FN binding in myeloma cells are discussed.

B-Lymphocytes↗

HLA matching: identification of permissible HLA mismatches.

Previous studies of mismatches for a single HLA antigen in kidney transplants have not demonstrated that any single HLA antigen was more immunogenic than another. Here we show that certain mismatched antigens are "permissible" to recipients of certain types and not to others. In this retrospective study of 1,273 living-donor kidney transplants, a mismatch for 27 different, single A,B,DR antigens was evaluated with respect to recipients of various types. Various combinations of donor/recipient incompatibilities were then classified as "permissible" or immunogenic, depending upon the fate of the transplant. This list was then evaluated with 1,905 patients who received cadaver-donor transplants mismatched for a single A,B,DR antigen. Cadaver-donor kidney transplants judged to have received a permissible mismatch in the A, B, or DR loci had graft survival rates equivalent to zero-A,B,DR-mismatched grafts. Among 425 patients with one-A,B,DR-permissible mismatches, one-year graft survival was 89% with a 14.1-year half-life, compared with 966 one-A,B,DR-mismatched grafts with an 89% one-year survival and an 18-year half-life. Based upon these results, we recommend the initiation of one permissible A,B,DR-mismatched transplants for national sharing. This will result in potentially 60% of shared transplants having high long-term graft survival rates.

Graft Survival↗

HLA matching: maximizing the number of compatible transplants.

1. Less than 10% of the cadaver kidneys currently allocated have 0-B,DR mismatches. 2. Up to 15% of the kidneys could be regionally allocated using the UNOS algorithm to 0-B,DR-mismatched recipients with a projected 67% 5-year graft survival. 3. Twice the number (32%) of recipients can be identified with zero of 10 A,B residues mismatched with the same 67% 5-year survival. 4. Another doubling (68%) of compatible recipients can be identified with zero of 7 DR supertypic determinants (4 DQ and 3 DRB) and zero of the A,B residues mismatched with a 66% 5-year graft survival. 5. Compressing A,B, and DR antigens to supertypic determinants reduces the racial differences in HLA to the point that 90% of kidneys can be allocated to Black recipients with zero of 3 DRB and zero A,B residues mismatched.

Black People↗

Thirty-year trends in clinical kidney transplantation.

Trends in one-year graft survival rates seen in the past 30 years were examined in the UCLA and UNOS Registries. Some of the trends noted were as follows: 1. One-year graft survival rates for cadaver-donor transplants improved from 40% to 80% during this 30-year period. One-year patient survival improved from 50% to 95%. Transplants from living-related donors improved in graft survival from 80% to 90-95%. 2. Factors that diminished in importance were: recipient race, sensitization, primary disease, HLA haplotype matching in living donors, recipient and donor sex, kidney sharing, and transfusions. 3. Factors that continue to provide about a 10% variation of one-year graft survival are: cold ischemia time, HLA mismatch, recipient and donor age. 4. Posttransplantation, factors such as first-day diuresis, one-week dialysis, rejection at discharge, and discharge serum creatinine continue to be very important determinants of future outcome in 6 yearly subsets of patients. 5. Induction by ALG and OKT3 was shown in 6 subsets to have no effect on one-year graft survival. 6. Future trend studies will be needed to examine the 5-year long-term effects.

Adolescent↗

Survival of nationally shared, HLA-matched kidney transplants from cadaveric donors. The UNOS Scientific Renal Transplant Registry.

BACKGROUND: The importance of HLA histocompatibility typing to the outcome of transplantation of cadaveric kidneys has been controversial. Four years ago, a prospective trial began in all U.S. transplantation centers to determine whether the results of transplantation would improve with the nationwide shipment of kidneys from cadaveric donors to waiting patients undergoing dialysis when there was a match at the HLA-A, B, and DR loci. METHODS: A total of 1386 cadaveric kidneys were shipped from 108 organ centers to 198 transplantation centers and distributed among HLA-matched recipients, 1004 of whom were receiving a first transplant and 382 of whom were receiving a subsequent transplant. Graft survival in these recipients was compared with that in 22,188 recipients of first transplants and 3950 recipients of subsequent transplants whose HLA antigens differed from those of the donor. RESULTS: The rate of graft survival at one year in recipients of HLA-matched first transplants was 88 percent, as compared with 79 percent in the recipients of mismatched grafts (P less than 0.001). The estimated half-life of the kidney after the first year was 17.3 years for matched grafts, as compared with 7.8 years for mismatched grafts (P = 0.003). Among paired kidneys from 470 donors, one-year graft survival was 87 percent in the recipients of matched first grafts, as compared with 80 percent in the recipients of the contralateral kidneys, who did not have HLA matches with the donors. In donors and recipients matched for the more highly defined split Class I and Class II HLA antigens, the rate of graft survival after one year was as high as 90 percent. CONCLUSIONS: The collaborative renal-transplantation program for HLA matching of donors and recipients yielded an increased rate of one-year graft survival and an estimated half-life for matched grafts twice that for mismatched grafts. An increased role for HLA matching in kidney allocation is therefore indicated.

Adolescent↗

HLA matching: a comparison of conventional and molecular approaches.

1. The UNOS national sharing program has produced a 5-fold increase in the number of compatible transplants since 1987. 2. Transplants with 0 broad HLA-antigen mismatches had 87% 1-year graft survival and an 18-year half-life, essentially the same result as with conventional matching. 3. Equally impressive results were obtained with public determinant matching: 1-year graft survival ranging from 84 to 88% and a half-life of 12-15 years. 4. Increasing the number of matched determinants improved the results but reduced the number of compatible recipients identified. 5. Less than 10% of the current transplants have 0 public determinants mismatched. This fraction could be increased to 66% with local sharing and to over 90% with national sharing. 6. The results for cadaver transplants would approach those of related kidneys if compatible grafts were transplanted at the 90% rate obtainable with molecular matching.

Cadaver↗

Effect of mismatching serologically defined residues on kidney transplant survival.

Amino acids within the HLA class I and II molecules were first examined individually for correlation with antibody reactions of over 50,000 antisera. The amino acids that correlated with the serologic reactions were classified as serologically defined: approximately half of the amino acids fell within that category, and the other half were employed as controls. The cadaver donor kidney transplant survival for patients who were mismatched for each of the sera-defined amino acids were compared to mismatches of the nonserologically defined amino acids. No differences were noted in the graft survivals of patients with mismatches for the serologically defined amino acids of HLA-A, -B, and -DR loci and for the nonserologically defined amino acids. Since many of the patients also had additional amino acids of mismatch, we cannot yet conclude that the serologically defined amino acids do not significantly influence graft outcome. In other words, the test may not have been sensitive enough to detect the degree of immunogenicity that may exist. However, we can conclude that mismatches for no single amino acid are strongly immunogenic.

Amino Acid Sequence↗

National allocation of cadaveric kidneys by HLA matching. Projected effect on outcome and costs.

BACKGROUND: Although receiving a cadaveric kidney matched at the HLA-A, B, and DR loci enhances graft survival in cyclosporine-treated patients, the value of a national system of kidney allocation based on HLA matching, with the attendant increased likelihood of better matching, is still questioned. Some fear that the costs of a national system are unjustified when only a small fraction of donors would exactly match any of the 16,000 potential recipients anyway. We estimated the effect on graft survival of the use of HLA matching for all allocations of cadaveric kidneys in the United States. METHODS: The graft-survival rates in five mutually exclusive groups of transplants with increasing numbers of HLA mismatches were estimated by partitioning the data for 22,190 first-time recipients of cadaveric kidneys. Overall graft survival was projected as a weighted average with use of the percentages of transplants in the hierarchical groups in recipient waiting pools of various sizes. We compared the benefits and costs of HLA matching in a national system with those of introducing cyclosporine, which was projected to enhance graft survival by 7 percentage points at 10 years. RESULTS: Sharing kidneys nationally on the basis of hierarchical HLA matching was estimated to enhance graft survival by an additional 5 percentage points at 10 years. The anticipated five-year cost of national allocation of kidneys by HLA matching for 7000 recipients, including consideration of the costs of graft removal and dialysis after transplant rejection, would be +4F6.5 million less than the cost of using cyclosporine alone. CONCLUSIONS: The use of an HLA allocation system will not add to the cost of renal transplantation, but it will improve the long-term results to the same extent as cyclosporine. We propose the initiation of a national kidney-sharing system based on hierarchical levels of HLA matches.

Cadaver↗

HLA epitopes and graft survival.

1. The fraction of patients and graft survival was provided for amino acid residues, heptapeptides, and conformational epitopes with HLA specificities of up to 7 antigens mismatched. 2. Mismatching large numbers of serologically defined residues was detrimental to graft survival, whereas nonserologically defined residues did not have an effect. 3. The difference in graft survival for those with a few and those with many conventional A,B,DR mismatches was doubled by counting serologically defined peptide epitopes. 4. The attempt to create conformationally defined epitopes by taking adjacent variable residues did not provide a good correlation with graft outcome.

Amino Acid Sequence↗