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Biomedical subjects

S Takemoto

Publications and source records attributed to S Takemoto.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of changes in the criteria for nationally shared kidney transplants for HLA-matched patients.

BACKGROUND: Nine years ago, a prospective trial began in all U.S. transplant centers to determine whether the results of renal transplantation would improve with the nationwide shipment of kidneys from cadaveric donors to HLA-matched patients. Since then, the stringency of criteria for HLA matching have been liberalized twice, from sharing only those kidneys that matched at all six HLA-A, -B, -DR antigens, to sharing phenotypically HLA-matched kidneys, and most recently to sharing zero HLA-mismatched kidneys. METHODS: Data reported to the United Network for Organ Sharing Scientific Renal Transplant Registry from October 1987 to December 1996 were analyzed to examine the transplant results of nationally shared HLA-matched kidneys and the effects of changes to the HLA matching criteria on graft survival and the distribution of HLA-matched kidneys. RESULTS: The overall 1-year graft survival rate of 5102 HLA-matched transplants was 88% compared with 81% for 58,207 recipients of kidneys with at least one HLA mismatch (P < 0.001). HLA-matched kidneys had a projected 12-year graft half-life, 50% higher than the 8-year half-life of mismatched grafts (P < 0.01). After the first change in the match criteria in August 1990, 1365 phenotypically matched kidneys with fewer than six HLA antigens identified had an 89% 1-year graft survival rate compared with 84% for 466 six antigen-matched kidneys transplanted before the change. After March 1995, 1067 zero HLA-mismatched kidneys that were not phenotypically identical nor six antigen matched, had a 1-year graft survival rate of 88%. Graft survival has not decreased as a result of these changes in the criteria for national sharing, despite an increase in the percentage of matched transplants from 2.5% during the six antigen-match era to 15.5% during the zero antigen-mismatch era. CONCLUSIONS: Changes to the United Network for Organ Sharing policy for national sharing of HLA-matched kidneys have increased the number of patients, and especially minority patients, who can benefit by receiving a well-matched graft without compromising the high graft survival rates provided by an HLA-matched kidney.

Cadaver↗
PubMed1998

Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes.

To examine the role of bone morphogenetic protein (BMP) signaling in chondrocytes during endochondral ossification, the dominant negative (DN) forms of BMP receptors were introduced into immature and mature chondrocytes isolated from lower and upper portions of chick embryo sternum, respectively. We found that control sternal chondrocyte populations expressed type IA, IB, and II BMP receptors as well as BMP-4 and -7. Expression of a DN-type II BMP receptor (termed DN-BMPR-II) in immature lower sternal (LS) chondrocytes led to a loss of differentiated functions; compared with control cells, the DN-BMPR- II-expressing LS chondrocytes proliferated more rapidly, acquired a fibroblastic morphology, showed little expression of type II collagen and aggrecan genes, and upregulated type I collagen gene expression. Expression of DN-BMPR-II in mature hypertrophic upper sternal (US) chondrocytes caused similar effects. In addition, the DN-BMPR-II-expressing US cells exhibited little alkaline phosphatase activity and type X collagen gene expression, while the control US cells produced both alkaline phosphatase and type X collagen. Both DN-BMPR-II-expressing US and LS chondrocytes failed to respond to treatment with BMP-2 . When we examined the effects of DN forms of types IA and IB BMP receptors, we found that DN-BMPR-IA had little effect, while DN-BMPR-IB had similar but weaker effects compared with those of DN-BMPR-II. We conclude that BMP signaling, particularly that mediated by the type II BMP receptor, is required for maintenance of the differentiated phenotype, control of cell proliferation, and expression of hypertrophic phenotype.

Animals↗
PubMed1997

Proliferation of adult T cell leukemia/lymphoma cells is associated with the constitutive activation of JAK/STAT proteins.

Human T cell leukemia/lymphotropic virus type I (HTLV-I) induces adult T cell leukemia/lymphoma (ATLL). The mechanism of HTLV-I oncogenesis in T cells remains partly elusive. In vitro, HTLV-I induces ligand-independent transformation of human CD4+ T cells, an event that correlates with acquisition of constitutive phosphorylation of Janus kinases (JAK) and signal transducers and activators of transcription (STAT) proteins. However, it is unclear whether the in vitro model of HTLV-I transformation has relevance to viral leukemogenesis in vivo. Here we tested the status of JAK/STAT phosphorylation and DNA-binding activity of STAT proteins in cell extracts of uncultured leukemic cells from 12 patients with ATLL by either DNA-binding assays, using DNA oligonucleotides specific for STAT-1 and STAT-3, STAT-5 and STAT-6 or, more directly, by immunoprecipitation and immunoblotting with anti-phosphotyrosine antibody for JAK and STAT proteins. Leukemic cells from 8 of 12 patients studied displayed constitutive DNA-binding activity of one or more STAT proteins, and the constitutive activation of the JAK/STAT pathway was found to persist over time in the 2 patients followed longitudinally. Furthermore, an association between JAK3 and STAT-1, STAT-3, and STAT-5 activation and cell-cycle progression was demonstrated by both propidium iodide staining and bromodeoxyuridine incorporation in cells of four patients tested. These results imply that JAK/STAT activation is associated with replication of leukemic cells and that therapeutic approaches aimed at JAK/STAT inhibition may be considered to halt neoplastic growth.

Adult↗
PubMed1997

Human recombinant tissue-factor pathway inhibitor prevents the proliferation of cultured human neonatal aortic smooth muscle cells.

Tissue-factor pathway inhibitor (TFPI) inhibits the procoagulant activity of the tissue-factor/factor VIIa complex. It was recently reported that TFPI prevented restenosis following tissue injury in a rabbit atherosclerotic model. In order to clarify the mechanism behind this successful prevention of restenosis, we investigated the direct effect of human recombinant TFPI (h-rTFPI) on the proliferation of cultured human neonatal aortic smooth muscle cells (hSMC). We found that h-rTFPI exhibits inhibitory activity toward hSMC proliferation, while h-rTFPI-C which lacks the carboxyl (C)-terminal region does not. Furthermore, we found that h-rTFPI binds to hSMCs with K(d) = 526 nM but that this binding is inhibited by the addition of the synthetic C-terminal peptide, Lys254-Met276, to h-rTFPI. Thus, the interaction of h-rTFPI with hSMCs mediated via the C-terminal region is responsible for the anti-proliferative action of h-rTFPI. On the basis of these results, we presume that the anti-proliferative effect of h-rTFPI in addition to its anticoagulant function plays a significant role in preventing restenosis following tissue injury.

Amino Acid Sequence↗
PubMed1997

HTLV-I provirus in the clinical subtypes of ATL.

Adult T cell leukemia (ATL) is an aggressive neoplasm of mature helper T cell, which is etiologically linked with human T-lymphotropic virus type 1 (HTLV-I). We studied HTLV-I provirus in 61 cases of ATL with Southern blot analyses and long PCR. These methods detected defective virus in 34 cases (56%). Furthermore, it found two types of defective virus. The first type (type 1) defective virus had both LTRs, but lacked internal sequences, such as gag and pol. Type 1 defective virus was seen in 50% of all defective virus. The second form (type 2) of defective virus had only one LTR, and 5'-LTR was preferentially deleted. This type of defective virus could be more frequently detected in aggressive types of ATL (16/44 cases) than chronic type (1/17 cases). This defective virus might be associated with clinical subtype.

Adult↗
PubMed1997

Significance of the donor age effect on kidney transplants.

The shortage of cadaveric donor kidneys for transplantation has forced a re-evaluation of the limits on donor age acceptability. However, as more kidneys from older donors have been transplanted, a significantly lower graft survival has been noted among their recipients. The impact of utilizing older donor kidneys and the relative importance of donor age with respect to other factors has not been clarified. A total of 43,172 cadaver donor transplants reported to the UNOS Scientific Renal Transplant Registry between 1987 and 1995 were the subjects of this study. Cox regression analysis was utilized to assess the joint effects on graft survival of donor age and HLA mismatch, recipient sex, race, age, original disease, donor death cause, cold ischemia time, and transplant year. Increased first day anuria, dialysis requirement, and discharge serum creatinine were noted with increasing donor age. Moreover, long-term graft and patient survival diminished as donor age increased. The 5-yr graft survival of zero HLA-A,B,DR mismatched kidneys fell steadily from 81% when the donor was aged 21-30 to 39% when the donor was over age 60. The reported causes of kidney transplant failure were remarkably similar for old and young donors. The best transplant results were obtained with zero HLA-A,B,DR mismatched transplants from young donors and the worst with older donor kidneys, regardless of HLA compatibility. We calculated that up to 21% of kidney failures resulted from insufficient renal mass due to age and were incorrectly attributed to chronic rejection.

Adolescent↗
PubMed1996

Fit and match hypothesis for kidney transplantation.

The importance of HLA matching for cadaver-donor transplants is often ignored due to the small (10%) difference in graft survival rates between the best and worst matched pairs. A new "fit and match" hypothesis is proposed to improve the predictive value of matching. Graft and functional survival rates of kidney transplants were calculated for living and cadaver-donors by the standard Kaplan and Meier methods. Mean discharge serum creatinine (SCr) values were computed after excluding patients who died or lost their grafts before discharge. Donor size, recipient size, age of donor kidney, damage caused by cold ischemia time, and mode of donor death all had substantial effects on the average SCr levels at discharge. These SCr levels correlated with one- and five-year graft survival rates. Transplants that had extremely different graft survival rates, such as those from living donors and cadaver donors, were found to have similar rates when reclassified by SCr levels at discharge. By examining the combined effects of the fit and match factors, transplants with the best fit and match exhibited a 95% one-year graft survival rate, whereas those with the worst fit and match had a 75% survival rate. This 20% difference increased to 36% after five years (84% vs. 48%). We conclude that the fit and match hypothesis provides a theoretical basis for devising a more critical method of predicting cadaver kidney transplant survival rates. Furthermore, it suggests a vital need to develop methods for estimating functional donor renal mass.

Age Factors↗
PubMed1996

Delay of the denervation process in skeletal muscle by sensory ganglion graft and its clinical application.

We examined the effects of dorsal root ganglion isografts on the denervation process of skeletal muscle. A segment of sciatic nerve was removed from each of 25 inbred Wistar-Kyoto rats. Fifteen were set aside as controls. In the remaining 10 rats, isogeneic cervical dorsal root ganglia were grafted to the severed distal stump of the common peroneal nerve. Between day 72 and day 286 postoperatively, both controls and recipients were killed after twitch and tetanic tension recording of the extensor digitorum longus was performed. The wet muscle weight and the twitch and tetanic tensions of the denervated extensor digitorum longus in the graft group were significantly greater than those in the control group. The mean area of the denervated tibialis anterior muscle fibers in the graft group also was significantly larger than that in the control group. In electron and light microscopic images, nerve cells along the periphery of each dorsal root ganglion were found surviving with regenerating axons throughout the experimental period. Numerous myelinated axons were observed in the common peroneal nerve of the graft group, and there were significantly more axonal branches in the extensor digitorum longus of the graft group than in the extensor digitorum longus of the control group. Thus sensory nerve fibers from the grafted dorsal root ganglia had certain beneficial effects to slow the denervation process, presumably secreting trophic factors into the denervated muscle. Clinically, we have transferred avulsed dorsal root ganglia in cases of total brachial plexus avulsion directly into denervated skeletal muscle. This procedure, accompanied by nerve crossing procedures, will probably keep denervated skeletal muscle in a better condition until regenerating motor axons from the repair site reach their target muscle.

Animals↗
PubMed1996

DNA diagnosis of HTLV-I.

Human T-lymphotropic virus type I (HTLV-I) was the first retrovirus which was directly associated with adult T-cell leukemia (ATL). Infection with HTLV-I can also lead to various other diseases, e.g. HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-I uveitis, possibly via induction of immunodeficiency or hyperreactivity against HTLV-I-infected cells. Epidemiological data have shown that patients who developed these diseases represent a small percentage of HTLV-I-infected individuals living in restricted geographical areas. The identification of HTLV-I-infected individuals using serological and DNA-diagnostic methods is important because knowledge of HTLV-I seropositivity may help to prevent the transmission between sexual partners, as well as transmission from mother to child and blood transfusion. It also assists in establishing a diagnosis of ATL, HAM/ TSP and other HTLV-I-associated diseases.

DNA, Viral↗
PubMed1996

Reduced vasodilator response of the right coronary artery to myocardial ischemia in the hypertrophied right ventricle.

The reduced reactive hyperemic response of the right coronary artery (RCA) to brief coronary occlusion was assessed in dogs with pressure-induced right ventricular hypertrophy (RVH). Right coronary reactive hyperemia was observed in normal dogs and in dogs with pressure-induced RVH. RVH was induced by chronic pulmonary artery banding in eight 3- to 6-month-old dogs, and reactive hyperemia responses to coronary occlusion lasting for 5, 10, 15, 20, 30, 45, and 60 sec were compared to those in normal dogs. In dogs with RVH, the peak reactive flow rate and excess blood flow debt repayment after the release of 5- to 60 sec RCA occlusion were markedly attenuated. The calculated minimum coronary resistance was higher in RVH dogs than in normal dogs (p < 0.02). The occlusion time that produced one-half of the maximum %PRHc, T1/2, was significantly (p < 0.01) shorter in RVH dogs than in normal dogs, where %PRHc = (peak reactive flow rate baseline flow rate)/(baseline flow rate). T1/2 in RVH dogs varied inversely with right ventricular systolic pressure. Therefore, blood flow in the RCA in RVH is characterized by an attenuated flow response to acute myocardial ischemia, suggesting inadequate development of the coronary vasculature supplying the hypertrophied ventricle.

Animals↗
PubMed1996

Primary adult T cell leukemia of bone: two patients with primary bone lesion showing monoclonal integration of HTLV-I proviral DNA.

Adult T cell leukemia (ATL), a neoplasm of mature helper T lymphocytes is etiologically associated with human T lymphotropic virus type-I (HTLV-I). ATL cells infiltrate various organs, the lung, skin, central nervous system, gastrointestinal tract, and bone, causing various clinical manifestations. Two unusual cases of ATL, in which lytic bone lesion was the primary site of ATL, are described. One patient had multiple lytic lesions in bones without any involvement of other organs, and the other patient had a bone lesion in the right radius, which disappeared after chemotherapy. In both cases, monoclonal integration of HTLV-I provirus was demonstrated in the genomic DNA from each bone lesion. Although their clinical courses and pathological findings were different, ATL in both patients began as a bone lesion, showing that primary lymphoma of bone can be manifested in ATL cases.

Adult↗
PubMed1996

Twenty-year follow-up on the effect of HLA matching on kidney transplant survival and prediction of future twenty-year survival.

The difficulty in achieving long-term survival is demonstrated by the fact that an improvement of 30 percentage points in 1-year cadaver donor survival resulted in only a 10-percentage point improvement over 20 years. In early transplants from 1965 to 1974, the 20-year survival rate of HLA identical siblings was 46%, of parental donors 27%, and of cadaver donors 12%. More recent grafts, performed since 1987, had a projected survival of 57% for identical donors, 30% for parental donors, and 18% for cadaver donors. With respect to HLA matching for cadaver donor kidney transplants, a 0 AB-antigen mismatch produced higher graft survival than did mismatched transplants during the 20-year period from 1965 to 1984. After the introduction of HLA Class II typing in 1980 and general improvements in typing for transplants performed after 1987, the 0 ABDR-mismatched grafts have a projected 20-year survival of 40%. The projected survival rates for transplants with one or more mismatches fall progressively to 13% for transplants that have 6 ABDR mismatches. Thus, the success due to HLA matching has improved ever since the introduction of cyclosporine because of the concurrent improvements in tissue typing for Class I and Class II specificities.

ABO Blood-Group System↗
PubMed1996

HLA compatibility can be predicted by matching only three residues with outward oriented sidechains.

A new method of residue matching based on three polymorphic upward-oriented amino acid residues on the alpha-helices of the HLA molecule is described. The projected 10-year graft outcome for 1232 transplants with none of these residues mismatched was 47%, essentially the same as for 0 BDR-mismatched kidneys. The projected impact of allocation to recipients in a local pool based on the three residues was a 5% improvement in overall graft survival at 10 years.

Amino Acid Sequence↗
PubMed1996

Risk rate and long-term kidney transplant survival.

The findings from the UNOS Scientific Renal Transplant Registry are summarized in the following table. We've also provided our opinions on ways to influence the risk factors in the Discussion section. [table: see text]

Adolescent↗