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Biomedical subjects

S Takemoto

Publications and source records attributed to S Takemoto.

At least 91 records · Page 5Linked to original sources

UCLA and UNOS Registries. Overview.

The subjects of this study were transplant recipients entered in the UCLA Registry file since 1984 and in the UNOS Registry since 1987. [table: see text] 5. Based on the data above, we conclude that the near 20% loss rate in the first year can be roughly allocated as follows: death 3%, technical 3%, agonal kidney damage 6%, and histocompatibility differences 7%. 6. The quality of HLA typing was assessed by examining the frequencies of the various specificities reported for cadaver donors in 8 yearly periods from 1984 to 1991. The A and B loci specificities were remarkably constant. The DR specificities were still undergoing stabilization. 7. No urine output on the first day, which occurred in approximately 10% of the first cadaver-donor transplants, resulted in about a 20 percentage point lower graft survival rate at 1 year. 8. Anuria on the first day increased with cold ischemia time, donor age, cerebral vascular accident donors, and retransplant recipients. 9. Graft survival with anuria on the first day and: [table: see text] 10. When dialysis was required during the first week, there was an approximate 15 percentage point decrease in 1-year graft survival in 25% of the patients. 11. One rejection in the first hospitalization period resulted in 67% 1-year graft survival. More than 1 rejection led to 57% 1-year graft survival. 12. Serum creatinine at discharge was an accurate indicator of subsequent graft survival. Approximately a 7 percentage point drop in 1-year graft survival was noted with each unit of serum creatinine above 2.0 mg/dl.

Adolescent↗

HLA peptide matching.

Thirty-eight HLA-A and -B locus specificities, for which the amino acid sequence is known, were cut by computer into all possible peptides composed of two to seven amino acids. These peptides were compared among the different specificities, and those that were unique were identified. For example, there were 375 unique tripeptides when considering both the A and B locus. The 1-year kidney graft survival was determined for patients who were mismatched for each of the tripeptides. The peptides were ranked according to the associated graft survival, and the sum of the ranks was used as a mismatching score. The rank sum score produced promising results, for some degree of correlation was noted when tested against another set of patients transplanted without CyA, and a third set of those who received grafts from related donors. We conclude that matching for tripeptides of the HLA-A and -B locus is associated with graft outcome, and that this may be a more effective way of HLA matching for transplants, particularly since a higher fraction of patients fall into the high-survival category.

Amino Acid Sequence↗

A report from the UNOS Scientific Renal Transplant Registry.

The UNOS Kidney Transplant Registry is now fully operational. Aside from scientific reports from UCLA, analysis of the same data base from investigators who initiate projects through UNOS central in Richmond, as well as from HICFA and USRDS, can be anticipated. Plans are underway to simplify the reporting process. With the large number of accumulated cases, it should be possible to analyze many factors in the future. Presently, histocompatibility differences in living related vs cadaver donors and degrees of HLA mismatching among recipients of cadaveric kidneys are major factors. Immunization by transplant rejection is the second most important factor.

Graft Survival↗

Earlobe crease and atherosclerosis. An autopsy study.

The association between earlobe crease (ELC) and coronary and aortic atherosclerosis in 100 autopsied men ranging in age from 50 to 79 years, who died free of vascular diseases or related conditions, was studied in conjunction with blood pressure and serum total cholesterol (TC) levels. Earlobe crease was graded and defined as groups 1, 2, and 3 according to the depth and length in both ears. The extent of atherosclerosis in the coronary arteries and aortas was visually graded. Coronary atherosclerosis was significantly more severe in group 3 in all the decades examined than in groups 1 or 2. Aortic atherosclerosis in group 3 was significantly greater than in group 1 in all the decades examined, and was greater than in group 2 in the seventh and eighth decades. The TC level was significantly higher in group 3 than in groups 1 or 2 except in the sixth decade. Multivariate regression analyses demonstrated that the degree of ELC was dependent on the extent of coronary and aortic atherosclerosis, but was independent of age. Conversely, the extent of coronary atherosclerosis was dependent on the degree of ELC, but was independent of age. The extent of aortic atherosclerosis was, however, dependent not only on the appearance of ELC and TC, but on age. It is thus concluded that ELC provides a significant external marker for atherosclerosis and may reflect a persistent overload of atherosclerosis risk factors, such as TC.

Adolescent↗

Antihypertensive effect of tryptic hydrolysate of milk casein in spontaneously hypertensive rats.

1. Repeated oral administrations of tryptic hydrolysate of bovine milk casein (CEI) showed antihypertensive effect in spontaneously hypertensive rats. 2. Single oral administration of CEI antagonized the pressor response to angiotensin I. 3. Bovine milk casein hydrolysate inhibited the angiotensin I-converting enzyme (ACE) activity. Three peptides with ACE-inhibiting activity were isolated from CEI. 4. It is suggested that ACE-inhibiting peptides in the tryptic hydrolysate milk casein are absorbed from the intestinal tract and produce an antihypertensive effect.

Administration, Oral↗

Report on 604 six-antigen-matched transplants.

1. Two-year 6-antigen-matched graft survival was 82% for first grafts and 72% for second grafts compared to 72% and 60% for the controls. 2. Six-antigen-matched transplants had longer mean ischemia times and recipients had higher levels of antibodies but the effect of these factors was insignificant compared to their effect on the controls. 3. One reason for transplant loss among the 6-antigen-matched recipients was inadequate transplant size. When kidneys from young or old donors were transplanted into heavy recipients, graft survival was 74% compared to 88% for median-age donors. 4. Six-antigen-matched transplants with common phenotypes (greater than 4 cases) had 2-year graft survival of 87% compared to 76% for those which occurred only once. 5. Difficulties in tissue typing certain antigens was shown to have an effect. Six-antigen-matched transplants with antigens defined by at least 80% of the tissue typing laboratories had 89% 1-year graft survival compared to 73% for those with antigens which were more difficult to define. 6. There were fewer homozygous donors and more regraft transplants than expected.

Age Factors↗

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↗

Overview and epitope matching.

1. Kidney graft survival rates have stabilized over the past 4 years, suggesting that gains achieved with CsA have plateaued. The overall 1-year graft survival is 77% for first cadaver donor transplants, 90% for parental donors, and 93% for HLA-identical sibling donors. Patient survival for all categories is now over 95%. 2. The UNOS 6-antigen match program has resulted in outstanding graft survivals. Of 88 kidneys which were transplanted into first graft recipients, the 6-antigen match kidney had a 1-year graft survival of 91% compared to 74% for the contralateral kidney transplanted locally (p less than 0.008). 3. In highly sensitized patients with more than 80% PRA the shipped 6-antigen matched kidney had a 91% 1-year graft survival rate compared to 72% survival in comparable control patients from the registry (p less than 0.005). In patients with less than 80% PRA, 6-antigen matched kidneys had 90% 1-year graft survival compared to 80% in controls (p less than 0.00001). 4. The spread of 1-year graft survival rates at 68 centers that performed more than 100 transplants was 63-94%. The cumulative graft survival of 6-antigen matches performed at 129 different centers was 90%. Thus, the strong center effect was neutralized by the use of matched transplants. 5. In contrast to the 1% of patients who would receive O-B,DR mismatched transplants on a random basis, if kidneys were shared in the national pool, 74% could receive such a transplant. We therefore propose that a keep one-share one policy be adopted for all kidneys harvested in the United States. If no 0-B,DR mismatched patient is available, both kidneys will be kept by the harvesting center. Since 63% of kidneys are currently being shared with other centers for various reasons, the 75% sharing suggested by the new system should not impose a hardship on transplant centers. The UNOS payback agreement will be replaced by this agreement by which shipping will be done only to achieve excellent matches. 6. In order to achieve a better method of excluding the worst mismatches, an attempt was made to develop a new method of mismatching using amino acid sequences of the HLA specificities. Donor and recipient types can be converted to amino acid sequences and the mismatching done on the basis of amino acids of mismatch at each residue or position. For each residue, specific combinations of amino acid substitutions were examined individually to determine their effect on graft survival. From these studies, a list of "immunogenic" amino acids was prepared, and graft survival was then computed for increasing numbers of amino acids of mismatch.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

The UNOS Scientific Renal Transplant Registry.

1. After 2 years of data collection and compiling, the UNOS Scientific Renal Transplant Registry was analyzed for the first time. One-year graft survival rates were 89% for first parent donor transplants (257), 76% for first cadaver (7,049), 65% for second cadaver (1,072), and 57% for multiple retransplant recipients (221). 2. The side-by-side comparison of the UNOS and UCLA registries revealed a remarkable similarity between results from the 2 databases. The concordance between the registries makes us confident in the validity of the UNOS data and also suggests that centers submitting data to the voluntary UCLA Registry are representative of the national experience. 3. Eighty-nine recipients of 6-antigen matched first cadaver transplants were identified in the UNOS Registry with 88% graft survival at 1 year. This result is comparable to that obtained from surveys that identified 224 recipients with 90% graft survival at 1 year. These results underscore the importance of sharing cadaver kidneys to achieve perfectly matched transplants. 4. Blood transfusions improved graft survival by 5% at 1 year. More than one-quarter of the first cadaver transplant recipients were nontransfused. 5. The first follow-up report after discharge of the transplant recipient was requested at 6 months by UNOS. This delay in reporting transplant outcome resulted in a serious lag between the time a transplant was performed and its availability for analysis. The UCLA Registry collects a report at 3 months and had more recent transplants available for analysis.

Databases, Bibliographic↗

A report on 341 six-antigen matched transplants.

1. One-year graft survival for patients receiving 6-antigen matched transplants was 90% compared to 78% for control nonshipped, nonmatched kidneys. 2. Graft survival with more than 30 hours of cold ischemia time was 90% for 6-antigen matched transplants compared to 80% for control transplants with short cold ischemia times of less than 30 hours. 3. Among 188 paired kidneys in which 1 kidney was shipped and transplanted into a 6-antigen matched patient, the 1-year graft survival was 87% compared to 75% for the contralateral, nonshipped kidney. 4. Almost 40% of 6-antigen matched transplants were performed in sensitized patients. As many as 13% of the 6-antigen matched kidneys were grafted into highly sensitized patients. The 1-year graft survival of 32 patients with antibodies reactive to more than 80% of the random panel was 92% compared to 72% for transplants in similarly sensitized controls.

Adolescent↗

A comparison of kidney transplant survival in white and black recipients.

This study was an analysis of graft survival in patients transplanted during the 1984 to 1988 cyclosporine era. 1. The 1-year first cadaver donor graft survival rate was 77 in whites and 70 in blacks. This difference increased by the third year to 65 in whites and 49 in blacks. 2. The corresponding second graft survival was 67 for whites and 60 for blacks in the first year and 53 for whites and 39 for blacks in the third year. 3. The same graft survival was noted in whites for patients older than 15. For blacks, the 3-year survival for older patients (over 45 years of age) was higher (50%) than for those 15 to 30 years old (43%). 4. The yearly trend for whites has been that older patients have had graft survival equivalent to young patients. However, among blacks, survival in young patients did not improve with the introduction of cyclosporine, and survival of older blacks was the same as for older whites. 5. The difference in graft survival between whites and blacks was greater for young males than females. 6. In both races, immunologic failures occurred more often in young patients than in older ones. 7. Patients with various original diseases consistently showed superior survival in whites as compared to blacks. Only in SLE patients did blacks have higher survival rates. 8. The half-life of transplants in blacks was lower than in whites in the 1974 to 1979 period as well as from 1980 to 1988. The half-life was about 8 years in whites and about 4 years in blacks. 9. Parental donor and HLA-identical sibling donor grafts in blacks had about the same graft survival as corresponding grafts in whites. Thus, when the HLA chromosome had been matched, the race effect disappeared. 10. We postulate that noncompliance may have been the major factor resulting in lower graft survival in young black males. A suggested ideal solution to the problem is recruitment of more black cadaver donors in order to achieve excellent matches.

Black People↗

Donor age and recipient age.

Donor age. 1. Kidneys from older donors led to markedly lower graft survival than kidneys from younger donors. The 1-year first cadaver donor graft survival rates were 80% for recipients receiving kidneys from 16-year-old donors, 70% from 50-year olds and 57% from 65-year-old donors. This means that 1-year graft survival decreased 10% by donor age 50 and 23% by donor age 65. 2. The trend toward lower graft survival with older donors was most noticeable after 1985, suggesting that CsA treatment was primarily responsible for the effect. 3. Twelve percent of kidneys from donors over age 50 never functioned while the nonfunction rate of 17- to 30-year-old donor kidneys was only 2%. Forty-six percent of kidneys from younger donors functioned within 3 days, whereas 26% functioned in 3 days if they came from donors who were older than 50. 4. The tendency to use older donors has gradually increased in the past 10 years. Donors over 50 years of age comprised 5% of the donors in 1978 and rose to 10% by 1987. 5. Transfusions, HLA-B,DR mismatches, and causes of failure were not related to donor age. 6. In transplants performed in the last 10 years, donor age did not play a significant role in either patient or graft survival. Whether or not this will hold true for more recent CsA-treated transplants remains to be seen. Recipient age. 1. The most significant effect of recipient age for patients transplanted since 1983 was on patient survival: it dropped from 100% for 6- to 7-year-old recipients to 86% for 68- to 71-year olds. 2. There is an increased tendency to transplant patients older than 50. The number rose from 14% in 1978 to 25% in 1987. 3. A very strong association was noted between advancing recipient age and corresponding decrease in immunologic failures and increase in nonimmunologic failures. Immunologic responsiveness to allografts decreased with age, though failures from nonimmunologic causes increased with age. 4. Patients with no transfusions had increasingly higher graft survival with age: 63% 1-year graft survival for patients up to 20 years old and 73% for those over 50 which was consistent with the above findings. Transfusions led to 1-year graft survival of about 76% in all groups. Thus, transfusions had less effect in older recipients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Clinical transplants 1988. Overview.

1. The 3-month actual graft survival of 6-antigen matched transplants in the UNOS program was 96% compared to 85% in control kidneys which were not shipped (p = 0.004). Actuarial graft survival at 1 year was 89% for the 6-antigen matched kidneys and 78% for the controls (p = 0.02). 2. Several individual centers reported 1-year graft survival rates of 85-95% (in the first half of this volume). Various immunosuppressive protocols and attention to patient care resulted in high 10-year survival of 53% in 1 instance (Leuven). 3. The 1-year graft survival peaked at about 77% for transplants performed in 1985, 1986, and 1987. 4. Among transplants performed since 1984, HLA matching of cadaver donor transplants showed a 13% difference at 1 year between the best and worst A,B,DR matches, which expanded in 3 years to an 18% difference. 5. The center effect, which produces about a 13% difference in 1-year graft survival for cadaver donors, decreased to 0 in HLA-identical transplants. Thus, when the donor and recipient were histocompatible, all centers were able to achieve superior results. The results of the 6-antigen Match Study appear to validate this conclusion. 6. Preformed antibody is associated with a 9% decrease in graft survival for greater than 50% PRA in first grafts and 4% in second grafts. For peak antibodies, the difference was 7% for first grafts and 11% for second grafts. 7. Platelet flow cytometry in 23 patients with a positive flow cytometry crossmatch to T cells furnished a further refinement in grouping the patients. All 11 patients with a negative platelet crossmatch had functioning grafts at 1 month whereas only 5 of 12 patients with a positive platelet crossmatch had a functional graft at 1 month (p = 0.003). 8. The duration of first graft effect on the second graft has diminished considerably as immunosuppression improved. Patients whose first graft survived more than a year and who had a high 1-year graft survival of the second graft lost their second graft at an accelerated rate after the first year. At the end of 4 years, their survival was the same as that of the responder patients who had rejected their first grafts within 3 months. 9. False positive crossmatches, especially in "highly" sensitized patients were identified by the use of DTT. Transplants into 69 patients who were positive by the standard test but negative after DTT had a 94% 1-month function rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Cadaver↗

[A histochemical study of acid glycosaminoglycans on normal and pathological cartilage, ligaments and several other connective tissues].

Histochemical estimation of acid glycosaminoglycan was critically re-evaluated, using the meniscus, intervertebral disc, ossified yellow ligament, ganglion, Dupuytren's fascia and several other tissues. Each tissue was stained with toluidine blue, alcian blue, high iron diamine, low iron diamine, aldehyde fuchsin and dialyzed iron-ferrocyanide. Digestion techniques for GAG were used in these staining methods, and the effects of protease inhibitors (PI) on digestion were also examined. In this study, the optimal temperature for digestion with Streptomyces hyaluronidase was between 37 degrees C and 43 degrees C, which varied according to the tissue examined. The addition of PI seemed necessary because the enzymatic treatment without PI resulted in an excessive decrease of staining. Protease-free chondroitinase ABC, which did not excessively decrease staining results, was found to be more useful than chondroitinase ABC without PI.

Cartilage↗

Crossmatching with B and T cells and flow cytometry.

1. Hyperacute rejections occurred in 0.6% of 19,415 first cadaver donor grafts and 1.9% of 4,326 regrafts. When grouped into those without preformed cytotoxins, 0.5% first grafts and 1.3% of regrafts had hyperacute rejection. Among patients with cytotoxins 1.3% of first grafts and 2.6% of regrafts had hyperacute rejections. 2. A total of 923 first cadaver donor transplants and 238 multiple transplants were crossmatched by 6 variations of microcytotoxicity tests: standard, long 4-hour incubation, B lymphocytes at 4 degrees C and 37 degrees C and T lymphocytes at 4 degrees C and 37 degrees C. All crossmatching was done in one laboratory. 3. For first cadaver donor transplants, 178 patients with long positive crossmatches and 56 patients with T warm positive crossmatches had a significantly lower survival rate than crossmatch negative patients. Those with short positive (weak), B warm, B cold, and T cold positive crossmatches had the same graft survival as crossmatch negative patients. 4. In regrafted patients from cadaver donors those with a short and T warm positive crossmatches had lower graft survival than crossmatch negative patients. 5. Preformed T warm cytotoxins were associated with lower graft survival in first grafts and B warm cytotoxins were associated with lower graft survival in regrafts. 6. Eight patients with T warm positive crossmatches were successfully transplanted (function at 3 months) after they were shown to have IgM antibodies removable by 2-ME treatment. 7. A total of 136 patients were tested by FCXM at the time of transplant on a retrospective basis. Although all patients were crossmatch negative by the T warm tests, 24 were FCXM positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Antilymphocyte Serum↗

Disaggregation-induced changes of developmentally regulated proteins in Dictyostelium discoideum.

By means of two-dimensional gel electrophoresis, we analyzed proteins present in a slug-shaped tissue mass of D. discoideum and examined the changes in their amounts after disaggregation of the slugs. Of approximately one hundred polypeptides, six were found to decrease in amount after disaggregation. The decreases of four polypeptides were inhibited by the presence of 1 mM cAMP or 250 micrograms/ml cycloheximide. The decreases of the two other proteins were not suppressed by cAMP or cycloheximide. The patterns of proteins present in vegetative and aggregative cells were also examined. None of the six proteins which showed a decrease after slug disaggregation was found in vegetative or preaggregative cells. These results indicate that both synthesis and degradation of these proteins are controlled by cell-cell contact.

Cell Aggregation↗