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Biomedical subjects

S Takemoto

Publications and source records attributed to S Takemoto.

At least 55 records · Page 3Linked to original sources

High survival rates of kidney transplants from spousal and living unrelated donors.

BACKGROUND: In the United States, increasing numbers of persons are donating kidneys to their spouses. Despite greater histoincompatibility, the survival rates of these kidneys are higher than those of cadaveric kidneys. We examined the factors influencing the high survival rates of spousal-donor kidneys. METHODS: Kidney-transplant data from the United Network for Organ Sharing Renal Transplant Registry were used to calculate graft-survival rates with Kaplan-Meier analysis. RESULTS: The three-year survival rates were 85 percent for kidneys from 368 spouses, 81 percent for kidneys from 129 living unrelated donors who were not married to the recipients, 82 percent for kidneys from 3368 parents, and 70 percent for 43,341 cadaveric kidneys. The three-year survival rate for wife-to-husband grafts was 87 percent, which was the same as for husband-to-wife grafts if the wife had never been pregnant. If the wife had previously been pregnant, the three-year graft-survival rate was 76 percent (P = 0.40). The three-year graft-survival rate among recipients of spousal grafts who did not receive transfusions preoperatively was 81 percent, as compared with 90 percent for recipients who received 1 to 10 transfusions preoperatively (P = 0.008). The superior survival rate of grafts from unrelated donors could not be attributed to better HLA matching, white race, younger donor age, or shorter cold-ischemia times, but might be explained by damage due to shock before removal in 10 percent of the cadaveric kidneys. CONCLUSIONS: Spouses are an important source of living-donor kidney grafts because, despite poor HLA matching, the graft-survival rate is similar to that of parental-donor kidneys. This high rate of survival is attributed to the fact that the kidneys were uniformly healthy.

Adolescent↗

Systemic production of foreign peptides on the particle surface of tobacco mosaic virus.

By using a new tobacco mosaic virus (TMV) vector [Hamamoto, H., et al. (1993) Bio/Technology 11, 930-932], we have constructed TMV particles which present three different kinds of epitopes, two of them from influenza virus hemagglutinin (HA), and one from human immunodeficiency virus type I (HIV-I) envelope protein, on the surface of the particles. Each of these TMV particles reacted with each anti-peptide antiserum. These results suggest that this TMV vector can be used as an antigen presentation system.

Amino Acid Sequence↗

Adult T cell leukemia following HTLV-I-associated myelopathy/tropical spastic paraparesis: case reports and implication to the natural course of ATL.

Adult T cell leukemia (ATL) is the T cell malignancy caused by human T lymphotropic virus type I (HTLV-I), and HTLV-I is also the causative agent of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although HTLV-I causes both diseases, concomitant occurrence is reported to be rare. This paper describes two cases of HAM/TSP that developed into lymphoma-type ATL after the onset of HAM/TSP. In one case, the same HTLV-I infected clone could be detected by polymerase chain reaction in peripheral blood obtained when the patient was diagnosed as HAM/TSP. This finding showed that the HTLV-I clone already existed at the stage of HAM/TSP. Since frequent detection of clonal proliferation of HTLV-I infected cells has been reported previously in patients with HAM/TSP, careful follow-up is needed for patients with HAM/TSP.

Base Sequence↗

[Inhibitory effects of menogaril to the proliferation of HTLV-I infected T-cell lines and fresh tumor cells from adult T-cell leukemia patients].

Anti-cancer effect of anthracyclines are well established. In vitro inhibitory effects of a new anthracyclin-derivative drug, menogaril (TUT-7) which is developed for oral administration, on three human T-cell leukemia virus type-I (HTLV-I) infected T-cell lines, a HTLV-I non-infected T cell line, and fresh tumor cells from four adult T-cell leukemia (ATL) cases are evaluated and compared to those of doxorubicin. The inhibitory effects of TUT-7 is almost as much as those of doxorubicin. Both TUT-7 and doxorubicin induced apoptosis to a HTLV-I infected cell line and inhibited proliferation of fresh tumor cells from ATL of chronic, acute and lymphoma type in a dose dependent manner. We have already reported that skin eruption of ATL patient improved by oral administration of TUT-7. This new anthracyclin-derivative would be useful in treating ATL patients even in out-patients clinic keeping a good quality of life.

Apoptosis↗

The treatment of aneurysmal bone cyst.

Forty-four patients with aneurysmal bone cysts were treated with curettage with or without bone grafting, and in 26 (59%) recurrence developed. Of 11 patients treated with radiation, in only 1 (9%) the disease was not controlled. In 1 patient, radiation-induced sarcoma developed. Since the introduction of cryosurgery 27 years ago, 51 patients have been treated with cryosurgery. The patients had an average age of 13 years (range, 2-32 years). Thirty-four primary aneurysmal bone cysts and 17 secondary aneurysmal bone cysts occurred in association with 7 giant-cell tumors, 5 chondroblastomas, 2 fibromyxomas, 2 nonossifying fibromas, and 1 unicameral bone cyst. The tumors were classified as inactive in 9 patients, active in 31, and aggressive in 11. Treatment consisted of local intralesional excision followed by application of liquid nitrogen. The defect was either allowed to heal spontaneously (n = 26) or was reconstructed using an intramedullary rod (n = 2), bone grafts (n = 5), fibular strut grafts (n = 14), or polymethylmethacrylate with Steinmann pins (n = 4). At median followup of 85 months (range, 24-311 months), the overall cure rate was 82%. This was increased to 96% after a second, or repeat, cryosurgery. The disease in all patients eventually was controlled by cryosurgery. The mean functional rating was 90% (range, 63%-100%). Intralesional excision with adjunctive cryosurgery is an effective method for the treatment of aneurysmal bone cyst.

Adolescent↗

Sensitization and crossmatch.

A transfusion effect was observable in the half-lives of recent transplants. The half-life of non-transfused, nulliparous patients transplanted between 1992-1994 was 7.9 years compared to 9.1 years for transfused and 9.6 for retransplanted recipients. Patients whose PRA was measured by AHG were more likely to be broadly sensitized, had a significantly less frequent need for dialysis in the first week posttransplant, and had improved graft outcome regardless of their sensitization level. The decrease in the PNF rate from 10% in 1985 to 3% in 1994 can be attributed to improved crossmatch techniques. Patients with NIH- Flow+ or Wash- AHG+ crossmatches had significantly higher PNF rates. Broadly sensitized recipients (>50% PRA) treated with OKT3 or ALG induction therapy had half the incidence of hospital rejection and a 4-year survival rate of 62% compared to 55% for untreated recipients. Sensitized recipients of zero HLA-A,B,DR- and zero residue-mismatched kidneys had 4-year survival rates of 72% and 65%, respectively, compared with 53% for recipients of residue-mismatched grafts. National sharing has provided HLA-matched kidneys for broadly sensitized recipients. Nineteen percent of broadly sensitized recipients received a zero conventional or HLA residue-mismatched kidney. Regraft recipients matched for HLA residues had the same 4-year graft outcome (68%) as zero HLA-A,B,DR-mismatched recipients, regardless of sensitization level. Both conventional HLA matching and HLA-residue matching reduced the chance that a failed graft would result in broad sensitization. HLA matching was suggested to prevent broad sensitization of pediatric recipients. Half-life for broadly sensitized patients under 18 years of age was 4.9 years and their 4-year graft survival was only 45%.

Adolescent↗

Advances in kidney transplantation: 1985-1995.

Graphs and tables published 10 years ago in our Clinical Kidney Transplants 1985 book are compared to current analyses. Impressive progress is apparent over the past decade. During this period, the effects of factors such as transfusion and the duration of first grafts on second grafts have disappeared, while the effects of factors such as cold ischemia time, regrafts and original disease have diminished in magnitude. Other factors, including HLA matching, donor age and race, continue to exhibit significant influence. It should be emphasized that most of these comparisons apply to one-year graft survival. Thus, our attention must now turn to factors which influence 10-year graft survival. Though 10 years is considered long-term survival to transplant physicians, for patients, it is but a brief period of life.

Adolescent↗

A novel diagnostic method of adult T-cell leukemia: monoclonal integration of human T-cell lymphotropic virus type I provirus DNA detected by inverse polymerase chain reaction.

Adult T-cell leukemia (ATL) is neoplasm of the mature helper T lymphocytes and human T-cell lymphotropic virus type-I (HTLV-I) has been shown to be causative virus of ATL. Because HTLV-I integrates its provirus randomly into host chromosomal DNA, monoclonal integration of HTLV-I provirus indicates the clonal proliferation of HTLV-I-infected cells. Therefore, demonstration of clonality of HTLV-I proviral DNA is essential to diagnosis of ATL. Southern blot analysis was used for this purpose. We developed the novel method using inverse polymerase chain reaction (IPCR) to detect the clonality of HTLV-I proviral DNA. This method identified the clonality in all ATL cases. Diagnosis could be made within 3 days using this method. It enabled us to detect specifically the presence of minimal numbers of ATL cells with high sensitivity. It also identified the monoclonal or oligoclonal proliferations of HTLV-I-infected cells in HTLV-I carriers and the intermediate state, in which no clonality could be shown by conventional Southern blot analyses. This finding indicated that even HTLV-I carriers had monoclonal proliferation of HTLV-I-infected cells without any symptoms. This novel method is shown to be useful for the diagnosis of ATL and provides information on the natural course of HTLV-I infection.

Base Sequence↗

Equitable allocation of HLA-compatible kidneys for local pools and for minorities.

BACKGROUND: The methods used to allocate cadaveric kidneys in the United States have been criticized as being unfair to minorities because of an over-emphasis on HLA matching. We evaluated a new HLA-matching method that might alleviate this problem. METHODS: We used data from the United Network for Organ Sharing (UNOS) Kidney Transplant Registry to evaluate and project the outcome of cadaveric kidney transplantation. An HLA-matching method based on compatibility at 10 key amino acid residues of HLA-A and B molecules and a limited number of HLA-DR types was evaluated with use of the HLA types of the patients currently on the national waiting list and waiting lists in Los Angeles and Birmingham, Alabama. RESULTS: With national kidney sharing, the projected 10-year rate of graft survival for transplants in which there were no HLA-A, B, or DR mismatches was 66 percent, as compared with 39 percent for transplants with more than two HLA-A, B, or DR mismatches. With local sharing, 43 percent of patients could be fully matched, and they had a projected 10-year graft-survival rate of 50 percent. When one HLA-DR mismatch was allowed, the projected 10-year graft survival was 46 percent, and 67 percent of patients waiting locally could receive such grafts. Even in Alabama, where 68 percent of the patients on the waiting list are black, 48 percent of waiting patients could obtain a matched kidney. CONCLUSIONS: Inserting two new HLA-matching categories into the UNOS point system for cadaveric kidney allocation would increase the number of patients for whom matches could be found in local pools.

Black People↗

HLA matching for improved cadaver kidney allocation.

Because long-term results of kidney transplantation are still unsatisfactory, efforts are needed to improve them, particularly through the allocation of well-matched kidneys to recipients. In the past 7 years, the United Network of Organ Sharing 6-antigen match program has established that superior results can be obtained with the national sharing of available no HLA-A, -B, or -DR antigen mismatched kidneys. In addition to strengthening this program, the 1 HLA-A, -B, or -DR antigen-permissible mismatched kidneys should also be shared nationally. Approximately half of the recipients would receive nationally matched kidneys and the remaining recipients would be allotted kidneys locally, with distribution based on fewer risk factors (eg, residues) and on waiting points. This residue matching method was shown to result in more equitable kidney distribution to minorities.

Cadaver↗

Establishment of a monoclonal antibody to plasma cells: a comparison with CD38 and PCA-1.

A new monoclonal antibody which recognizes plasma cells was developed by utilizing two myeloma cell lines, KMS12PE (12PE) and KMS12BM (12BM), established from the pleural effusion and bone marrow, respectively, of the same patient. Since 12BM expresses CD20, CD38, and PCA-1 antigens, while 12PE has lost CD20, 12PE is considered to be phenotypically more mature than 12BM. The 12PE cells were used to immunize a BALB/c mouse and a MoAb was produced which was more reactive to 12PE than to 12BM. Thus, a clone, D2, was obtained. On Western blotting, D2 detected a single band of 54 kD under both reduced and non-reduced conditions. This antigen was not detected by Western blotting in peripheral blood lymphocytes that had been stimulated with pokeweed mitogen (PWM) for 7 days or in those not so stimulated. On flow cytometry, D2 detected a myeloma cell line, RPMI 8226. Another myeloma cell line, U266, was negative for D2 antigen. Staining various cell lines by D2 and other antiplasma cell antibodies, PCA-1 and CD38, showed that D2 is distinct from PCA-1 and CD38. The fresh myeloma cells of 14 myeloma patients were stained by D2 and for other plasma cell antigens. D2 strongly stained three samples obtained from patients with clinically aggressive myeloma, while CD38 stained all cases except one. PCA-1 was positive in nine samples and negative in five. PCA-1 expression was observed in plasma cells obtained from pleural effusion and peripheral blood, while PCA-1-negative cases were not found in such samples, suggesting that PCA-1 expression was related to extramedullary invasion. The morphology of the myeloma cells, classified according to Greipp's criteria, showed that there was no correlation between plasma cell antigen expression and plasma cell morphology. Analysis of D2 antigen expression should provide more information about the heterogeneity of myeloma cells.

ADP-ribosyl Cyclase↗

Refinement of permissible HLA mismatches.

Cadaver-donor transplants performed before 1987 that had survived for more than 7 years despite having all 6-A,B,DR antigens mismatched were used to develop a list of permissible mismatches. When these permissible mismatches were applied to an entirely different set of cadaver-donor grafts performed after 1987, patients with permissible mismatches had a higher graft survival than those with an equivalent number of immunogenic mismatches. In addition, a new list of permissible mismatches was produced from living-donor transplants which survived for more than one year despite having mismatches. When this list made from living-donor transplants was checked against cadaver-donor transplants, patients with one-permissible-A,B,DR mismatch had a projected 10-year graft survival equivalent to that of zero-A,B,DR mismatched transplants. Patients with one immunogenic mismatch had a significantly lower graft survival. Patients with only permissible mismatches had a higher graft survival than those with immunogenic mismatches and equivalent to patients with one immunogenic mismatch. It was projected that the percentage of patients who can benefit from a zero-A,B,DR mismatched transplant by national sharing can be doubled if one permissible-mismatched grafts are also shared. Even in local pools, the use of permissible-mismatched grafts can be projected to improve 10-year graft survival rates from the current 41% to 52%.

Adult↗

Establishment of a CD45-positive immature plasma cell line from an aggressive multiple myeloma with high serum lactate dehydrogenase.

A myeloma cell line (KHM-11) was established from the pleural effusion of a patient with IgA-kappa type aggressive myeloma with high serum lactate dehydrogenase who was extremely resistant to vincristin, adriamycin and dexamethasone combination therapy (VAD). The morphology of fresh tumor cells and KHM-11 was plasmablast according to Greipp's criteria. In addition to the expression of regular plasma cell antigens, CD38 and PCA-1, CD45 was found on both fresh cells and KHM-11. Other T- or B-cells antigens, such as CD2, 4, 8, 19, and 20 were negative. Cytoplasmic immunoglobulin kappa light chain in KHM-11 was found by flowcytometry. Southern blot analysis revealed that fresh sample and KHM-11 shared the same immunoglobulin gene rearrangement. IL-6 was found in the culture supernatant of KHM-11, and this supernatant stimulated the growth of this cell line, indicating an IL-6 autocrine mechanism. These findings indicate that KHM-11 is a CD45-positive immature plasma cell line. As far as we know, there is no report of CD45-positive myeloma cell line. KHM-11 should be a useful tool for understanding not only the pathogenesis of aggressive multiple myeloma with high LDH but also for understanding the mechanism which underlies the terminal differentiation of B-cells.

Antigens, Surface↗

A new tobacco mosaic virus vector and its use for the systemic production of angiotensin-I-converting enzyme inhibitor in transgenic tobacco and tomato.

We have developed a new tobacco mosaic virus (TMV) RNA vector and have used it initially to systemically produce an angiotensin-I-converting enzyme inhibitor peptide (ACEI) in tobacco and tomato plants. This vector incorporates a six base 3' context sequence, which permits readthrough of the stop codon for the TMV 130K protein gene, inserted between the stop codon for the coat protein (CP) gene and ACEI gene. In contrast to previous TMV RNA vectors, the new vector produced both an intact CP and a fused protein consisting of CP and ACEI (CP-ACEI). As a result, the vector could form virus particles and spread systemically from inoculated to non-inoculated leaves. In tomato plants, production of ACEI in fruit was also achieved.

Amino Acid Sequence↗