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T Kenmochi

Publications and source records attributed to T Kenmochi.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Organ Preservation].

Organ procurement is the first step of organ preservation. We have developed "in situ machine wash out technique with CMH solution" for the purpose of rapid cooling and complete elimination of blood. The utility of this technique was confirmed by both experimentally and clinically. Two major techniques have been used for organ preservation. One is a simple cold storage. Using this method, it is easy to transport organs for transplantation. In addition, availability of UW solution is another advantage of this method. The other is a continuous hypothermic perfusion. Despite of complexity and difficulty of organ transportation, this technique has some advantages, such as viability assay and pretreatment of organs before transplantation. In our experimental studies, viability assays of canine liver and pancreas were achieved using a organ perfusion machine. We also succeeded to prolong the survival of canine pancreatic allograft by pretreatment of anti-Ia antibody during perfusion. While, cryopreservation is most suitable for cell preservation like pancreatic islets. Recently, gene technology was applied for organ preservation studies. In the future, this might become a potent tool for studies in this field.

Cryopreservation↗
PubMed1995

Fetal pancreas transplantation in miniature swine. V. The functional and immunodulatory effects of ultraviolet light on fetal pig islets.

We have used the pig as a large animal model for studies of fetal pancreas transplantation. Fetal pig pancreas (FPP) has also been proposed as a potential source of endocrine cells for the treatment of diabetes mellitus. Among the approaches to prevent rejection, the irradiation of donor islets with ultraviolet B light has been used for its immunomodulating properties. Our goal was to study in vitro the effects of UV-B irradiation of FPP on the function and immunogenicity of the tissue. FPP were collagenase-digested and cultured for 1-29 days prior to UV-B irradiation. Static incubation tests were used to measure glucose-theophylline stimulated insulin release. Data obtained at 300 J/m2 revealed no impairment of insulin release (78% to 129% of controls, P = ns). At 500 J/m2, a significant reduction of glucose-theophylline stimulated insulin release was observed with 50-60-day-old FPP (35% to 66% of controls, P < 0.05), but not with 80-day-old FPP (93% of controls, P = ns). At both doses, prolonged observation in culture did not show any alteration of the growth and proliferation of islet cell clusters. UV-irradiated (300 J/m2) adult and fetal pig islet allografts released C-peptide and survived > 200 days. The immunogenicity of irradiated tissues was determined in vitro with allogeneic mixed islet-lymphocyte cultures (MILC). Proliferative responses of allogeneic lymphocytes to UV-irradiated FPP were very significantly decreased by 52-91% at both 300 and 500 J/m2 doses. This effect was observed from 1 to 10 days following UV irradiation and was not modulated by exposure of the tissues to gamma-interferon. We conclude that UVB-irradiation of FPP at a dose of 300 J/m2 does not alter its endocrine function and growth and is effective in reducing tissue immunogenicity. This treatment may be a useful approach for fetal islet transplantation in large animal models.

Animals↗
PubMed1995

Clinical islet transplantation experience of the University of California Islet Transplant Consortium.

BACKGROUND: The University of California Islet Transplant Consortium was formed to evaluate the feasibility of performing clinical islet transplantation at different transplant centers by using a single centralized islet isolation laboratory. METHODS: From July 1992 through February 1995 seven adult islet transplantations were performed, six allografts and one autograft. Once procured, human pancreata were brought to the UCLA-VA Islet Core Laboratory for islet isolation and purification, which were then transported to different centers for transplantation. Patients 1 through 3 received their transplants in Los Angeles, patient 4 received her islet transplant in Torrance, and patients 5 through 7 received their transplants in San Francisco. RESULTS: Although none of these patients achieved insulin independence, four of seven had functioning grafts longer than 6 months as indicated by circulating C-peptide level greater than 0.7 ng/ml. Furthermore, improved glucose control as shown by a decreased insulin requirement was seen in 57% (four of seven patients) of these patients. The ability to isolate islets at a single laboratory and transport them long distances to different centers was shown in patients 4 through 7. CONCLUSIONS: Islet transplantation can be performed with improvements in blood glucose control, and islets can be isolated at a centralized location and successfully transported to different centers for transplantation.

Adult↗
PubMed1995

Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function.

Allograft rejection is the major cause for failure in clinical islet transplantation for diabetic patients. A reduction of donor islet immunogenicity is potentially a useful approach for altering recipient's immune responses. Studies in animal models have shown the immunomodulatory properties of ultraviolet (UV)-B light that are beneficial for allograft survival. However, there is a narrow window between the doses required for immunomodulation and those toxic to beta-cells. In addition, this window varies between one species to another. Our study was designed to determine, in vitro, the UV-B dose for human islets that effectively reduces immunogenicity and maintains islet viability and normal function. Islets were isolated from donor pancreas by collagenase digestion and density gradient centrifugation on Euro-Ficoll. Static incubation and perifusion tests were used to measure glucose-stimulated insulin release. Viability was also assessed by histology and function of UV-irradiated islets transplanted under the renal capsule of athymic mice. The immunogenicity of UV-treated islets was determined in vitro with mixed islet lymphocyte culture using healthy human peripheral blood lymphocytes as responders. At a dose of 300 J/m2, both functional assays detected no impairment of insulin release. At 500 J/m2, a slight decrease of stimulated insulin release was observed only in the perifusion system. At the levels of 600 and 900 J/m2, a clear alteration was observed in both basal and stimulated insulin release. Islets irradiated at 300 J/m2 and transplanted into athymic mice stained strongly for insulin and responded to high glucose challenge in in vivo perfusion performed at two weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Human islet isolation in 104 consecutive cases. Factors affecting isolation success.

One of the major steps toward successful islet transplantation for the treatment of type diabetes is to obtain islets of sufficient number and viability. Using a standardized method of isolating islets, the goal of this study was to analyze the factors influencing the outcome of islet isolation. A total of 104 cadaveric human pancreata were processed for islets by the same team. Data from the islet-processing charts were reviewed retrospectively. The two endpoints were the recovery of islets, viable after 2 days of culture (group V = viable, group NV = nonviable) and the islet yield. Viable islets were recovered in 61% of cases (n = 63). Minimal blood glucose recorded during hospitalization was very significantly lower in group V (124 +/- 5 vs. 148 +/- 9, P = 0.01). Lack of significant medical history in the donor was associated with better viability as compared with various donor predispositions (chi-2 4.21, P = 0.04). Cold ischemia time (8.1 +/- 0.5 hr in group V vs. 9.8 +/- 0.9 hr in group NV, P = 0.07) and collagenase lot (5 lots tested, chi-2 13.1, P = 0.01) also affected the recovery of viable islets. Hospital time was shorter in group V (65.3 +/- 6.8 vs. 80.9 +/- 17.9 hr, P = 0.35). Multivariate logistic regression analyses of viable islet recovery identified minimal blood glucose (P = 0.03) and collagenase lot (P = 0.06) as the most significant risk factors. However, the best multivariate predictive model--which includes blood glucose, collagenase lot, donor age and surgical procurement team--correctly predicted 66.2% of cases only. Multivariate analysis of final islet yield designed hospitalization length, cardiorespiratory arrest, surgical procurement team, and collagenase lot as the best predictors. These data obtained in a large series of pancreata emphasized several donor and technical factors that should target the attention of islet transplant researchers in order to improve islet yield and viability.

Adolescent↗
PubMed1994

Swine as an allotransplantation model.

Because of their anatomical and physiological similarities to humans, pigs are well suited for solving technical problems associated with clinical transplantation. The availability of genetically defined strains of miniature swine is unique with this species, and has permitted the investigation, in a large animal model, of immunological and genetic aspects of allograft rejection, clinical manifestations associated with bone marrow transplantation, and the feasibility of various approaches for induction of transplantation tolerance. Immunological assays and various reagents are also available in order to pursue these studies.

Animals↗
PubMed1992

Prediction of viability of ischemically damaged canine pancreatic grafts by tissue flow rate with machine perfusion.

We studied the viability of canine pancreatic grafts using a short-time perfusion technique with an organ perfusion machine, "ORPH3000C". The following parameters were examined during perfusion of warm ischemically damaged grafts: Amylase, lipase, and insulin levels in the perfusate after 1-hr perfusion showed no significant correlation with warm ischemic time (WIT), and these indices could not be used to assess graft viability. Tissue flow rate (TFR) at the end of perfusion was significantly decreased with prolonged WIT. TFR correlated with the percent decrease in tissue SOD activity, thus TFR was a reliable predictor of reperfusion injury. Histological studies showed no findings attributable to warm ischemic injury before 1-hr perfusion. After 1-hr perfusion, the grafts were allotransplanted and the relation between TFR and endocrine function of the transplanted grafts was examined. TFR correlated with K value calculated from IV-GTT performed on day 5 postoperatively, suggesting that TFR is a predictable index of isolated pancreatic graft viability. Using TFR levels, this method allowed us to select only grafts with good function prior to transplantation. This technique appears to be of use for pancreatic transplantation from cadaver donors after cardiac arrest.

Animals↗
PubMed1992

[Experimental study on platelet activating factor and systemic circulatory failure caused by ischemic liver].

Ischemic hepatic failure is often accompanied by systemic circulatory failure. In hepatic graft failure, this circulatory derangement is reported to be cured by retransplantation. This suggests that ischemic liver might release some substance which causes circulatory depression. In the present study, the role of platelet activating factor (PAF) in systemic circulatory failure after liver ischemia was investigated. Partial hepatic ischemia was induced in ten dogs by clamping the afferent vessels to almost 70% of the liver for 60 minutes, and non-ischemic lobes were resected after declamping. Five were pretreated with 3 mg/kg of PAF antagonist (CV6209) i.v. (PAF antagonist group), and the others were pretreated with saline (control group). The mean arterial pressure markedly decreased after declamping in control group (89 +/- 25mmHg 25 min after declamping), but it did not fall in PAF antagonist group (155 +/- 221mmHg). Three died from either shock or hepatic failure within a week in control group, but none died in PAF antagonist group. In conclusion, ischemic liver was suggested to release PAF and depress systemic circulation. And a PAF antagonist was expected to be an effective drug for the circulatory derangement caused by ischemic liver.

Animals↗