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Biomedical subjects

J Tai

Publications and source records attributed to J Tai.

At least 55 records · Page 3Linked to original sources
PubMed1990

Successful banking of pancreatic endocrine cells for transplantation.

To determine optimal freezing and thawing conditions for rat pancreatic endocrine cells (PEC) and insulinoma cells, five different cryopreservation protocols were compared in this study. PEC and insulinoma cells were cooled at rates of between -0.3 degrees C/min and -5 degrees C/min to -70 degrees C in the presence of 10%, 15%, or 20% dimethylsulfoxide (DMSO) with a programmable temperature controller and then transferred to liquid nitrogen for storage. Frozen cells were thawed by either rapid (in 37 degrees C water bath) or slow (in air) thawing procedure. One hour after the thawing process, cellular viability was determined by trypan blue dye exclusion. The viability results for PEC and insulinoma cells were similar and showed that a slow cooling rate at -0.3 degrees C/min in combination with a rapid thawing in 37 degrees C water bath gave the best results, with up to 80% cellular viability. Cryoprotectant DMSO used at 10% concentration was the most effective among the three concentrations tested. Later, transplantation studies were performed with PEC cryopreserved with the best protocol, which is -5 degrees C/min to 4 degrees C, held for 3 minutes, -0.3 degrees C/min to -7 degrees C, held for 3 minutes, -0.3 degrees C/min to -40 degrees C, and -5 degrees C/min from -40 degrees C to -70 degrees C in 10% DMSO with a programmable temperature controller then transferred to liquid nitrogen for storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Human islet xenograft survival in diabetic rats. A functional and immunohistochemical study.

Prolonged survival of human islet xenografts under the kidney capsule of diabetic rats was achieved. Human islet xenograft survival time for the nonimmunosuppressed and single-dose antithymocyte serum-treated rats were 3.7 +/- 0.33 days (mean +/- SE, n = 6) and 4.2 +/- 0.63 (n = 4), respectively. In the recipients given 5 doses of ATS after islet transplantation, the graft survival time was significantly prolonged to 18.2 +/- 1.9 days (n = 6). An intravenous glucose tolerance test was performed on 3 recipients with a functional graft 12 days after xenotransplantation. The mean K rate was 1.44 +/- 0.43 (n = 3) compared with that of 2.1 +/- 0.14 (n = 5) found in normal control rats. Human C-peptide was present in the rat recipients following islet transplantation. In addition all 3 recipients showed significant basal human C-peptide values posttransplant and achieved levels of above 2.4 ng/ml during IVGTT. Morphologic and immunohistochemical examination of the islet grafts show that in recipients without immunosuppression or with a single dose of ATS, there was marked degree of fibrosis with little endocrine tissue left in the graft area by day 5. In contrast, the xenograft from recipients treated with 5 doses of ATS still contained well-preserved islet tissue with many insulin and glucagon containing cells on the day of graft removal when blood glucose had returned to the hyperglycemic level. Infiltration of the graft area with lymphoid cells (OX1+, OX8+, and W3/25+) was prominent, but they were not detected within the islets. Staining with monoclonal antibody clone L243 did not detect any expression of human class II antigen on the human pancreatic endocrine cells undergoing rejection by the host. This study has shown that with adequate immunosuppression human islet xenograft can normalize the blood glucose with prolonged survival time in diabetic rat recipients. The discordant xenotransplantation model used in this study would be useful for future xenotransplantation studies.

Animals↗
PubMed1989

Immunological studies in diabetic rat recipients with a pancreatic islet cell allograft in the brain.

Intracerebrally (IC) transplanted outbred Wistar and inbred Lewis (AgB1/1) strain rat islets and pancreatic endocrine cells (PEC) were able to function for a prolonged period in nonimmunosuppressed diabetic inbred ACI (AgB4/4) rats across a major histocompatibility barrier. All recipients were sensitized to various degrees to the donor antigens, as demonstrated by circulating cytotoxic antibody, irrespective of the survival of the IC graft. Nevertheless, the antidonor antibody titers in the IC islet and PEC graft recipients were lower and peaked later when compared with ACI recipients that received an intraportal islet allograft. PEC were also transplanted IC in immunized ACI recipients. In recipients hyperimmunized by repeated splenocyte injections, accelerated PEC graft rejection was observed. In recipients with weaker immunization by intraportal whole islet allograft 2 months prior to the IC allograft, the IC PEC allografts were also rejected. To assess if ACI rats with long-term-functioning IC islet/PEC allograft developed tolerance to the donor antigens, these animals were transplanted with a donor-strain skin graft. The skin grafts were all rejected in a first-set fashion similar to normal control ACI rats. Also, 7/12 and 7/9 recipients rejected their functional IC islet or PEC allograft, respectively, following transplantation of a donor-strain skin allograft, thus indicating that the transplanted PEC maintained their antigenicity even after long-term survival of over 1 year in allogeneic recipients. The data indicate that the brain does possess immunoprotective properties for the islet/PEC allograft. The protection, however, is relatively weak and is possibly due to the paucity of the effector mechanism in the brain relative to that normally present systemically.

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PubMed1988

Pancreatic islet allograft prevents basement membrane thickening in the diabetic rat retina.

Progressive basement membrane thickening is a characteristic structural abnormality in diabetic tissues including the retina. We examined the effect of pancreatic islet allotransplantation on basement membrane thickening and irregularities in retinal capillaries of the streptozotocin-diabetic rat. Diabetic animals received intraportal or intracerebral pancreatic islet allografts. Animals with functioning allografts demonstrated euglycaemia and a normal body weight gain during the 400-day post-transplantation period. The characteristic thickening of capillary basement membranes was completely prevented in animals with successful transplantation. The present findings suggest that islet allotransplantation may be a rational therapeutic approach in the treatment of diabetes mellitus and the prevention of ensuing secondary complications.

Animals↗
PubMed1988

Allotransplantation of dispersed single pancreatic endocrine cells in diabetic rats.

Dispersed pancreatic endocrine cells (PECs) were recently shown to survive indefinitely in the brain of allogeneic diabetic rat recipients across the major histocompatibility barrier without immunosuppression. Purified PECs (2-3 X 10(6) cells) prepared from Wistar rat islets were transplanted in 10 different sites in streptozocin-induced diabetic ACI rats. Blood glucose and body weight changes were monitored throughout the study. PEC isografts (n = 5) and allografts (n = 6) were nonfunctional when transplanted in intramuscular, intravenous, and intrahepatic sites. When transplanted intraportally (n = 6) and intraperitoneally (n = 6), similar grafts were functional but had a short survival period (6.6 +/- 1.5 and 15.3 +/- 16.6 days, respectively). Prolonged graft survival in some recipients was observed when kidney capsule [5, 9, 10, 240, 282, and 300 (2 rats) days], omentum pocket (7, 8, 10, 90, 105, 154, 155, and 157 days), and testis (7, 8, 12, 150, 230, and 234 days) were the transplantation sites. Permanent graft survival was achieved in 20 of 20 recipients with intracerebral transplantation and 21 of 22 recipients with intrathecal transplantation. These findings confirm that dispersed single PECs can be transplanted as a permanent functional graft and can normalize the hyperglycemia of the diabetic recipients. The duration of PEC graft survival is variable and depends on the transplantation site. Both the cerebral cortex and subarachnoid space, which are immunologically privileged sites, have provided the best allograft protection.

Animals↗
PubMed1988

Diabetic neuropathy in STZ-induced diabetic rat and effect of allogeneic islet cell transplantation. Morphometric analysis.

The effect of pancreatic islet cell allotransplantation on the development of diabetic neuropathy in streptozocin-induced diabetic ACI rats was examined morphometrically with light- and electron-microscopic procedures. Peripheral nerve function was evaluated by nerve conduction velocity and evoked muscle potential amplitude measurements. Diabetes was induced at 4 mo of age, and diabetic animals were transplanted by intracerebral and intraportal grafts 2 wk later. Diabetic animals with accepted grafts returned to euglycemia and showed a normal body-weight gain over the subsequent 14-mo observation period. Transplanted animals with accepted grafts and those in whom graft rejection was induced were compared with age-matched nontransplanted diabetic rats and nondiabetic control rats at 18 mo of age. Successful allotransplantation completely prevented axonal atrophy and the characteristic nodal and paranodal structural abnormalities in diabetic nerve, as well as the typical slowing of nerve conduction velocity. Our data suggest that islet cell allotransplantation is an effective therapeutic approach to the prevention of diabetic neuropathy.

Animals↗
PubMed1987

Antibodies against amino acids 1-15 of tumor necrosis factor block its binding to cell-surface receptor.

Human tumor necrosis factor (hTNF) mediates a variety of biologic activities, which are dependent on the attachment of hTNF to cell-surface receptors. To identify regions of the hTNF protein involved in binding hTNF to its receptor, we prepared five synthetic peptides [hTNF-(1-15), hTNF-(1-31), hTNF-(65-79), hTNF-(98-111), and hTNF-(124-141)] and two hydroxylamine cleavage fragments [hTNF-(1-39) and hTNF-(40-157)] of hTNF. The hTNF-synthetic peptides and hTNF fragments were tested in hTNF receptor binding assays and in two biologic assays: cytolysis of tumor cells and suppression of lipoprotein lipase in adipocytes. Neither the synthetic peptides nor hTNF fragments were active agonists or antagonists in these assays. The synthetic peptides were also conjugated to thyroglobulin, and peptide-specific antisera were raised. All five peptide-thyroglobulin conjugates induced antibody responses to the immunizing peptide and to hTNF. Each antiserum was tested for antagonist activity in hTNF binding assays. Only antisera raised against hTNF-(1-15) or hTNF-(1-31) and antisera against whole hTNF blocked binding. IgGs purified from these three antisera also block hTNF-induced cytolysis and lipoprotein lipase suppression. We conclude that antibodies that recognize the N-terminus of hTNF block the attachment of hTNF to its cellular receptor and inhibit the biologic effects of hTNF.

Antigen-Antibody Reactions↗
PubMed1987

Prevention of diabetic retinal capillary pericyte degeneration and loss by pancreatic islet allograft.

Degeneration and loss of retinal capillary pericytes are characteristic features of diabetic retinopathy. The effect of pancreatic islet cell allotransplantation across a major histocompatibility barrier on diabetic pericyte changes was examined in streptozotocin induced diabetic rats 14 months post-transplantation. Morphological studies of the retinal microvasculature were carried out using qualitative and quantitative morphological techniques. We describe significant prevention of pericyte degeneration and loss after successful allotransplantation suggesting that pancreatic islet allograft is a promising therapeutical approach in the prevention of diabetic retinopathy.

Animals↗
PubMed1985

Effect of endocrine pancreas allotransplantation on diabetic nerve dysfunction.

The effect of pancreatic endocrine tissue allotransplantation on the development of peripheral nerve dysfunction in streptozotocin induced diabetic rat recipients across major histocompatibility barrier was evaluated. Motor nerve conduction velocity (MNCV) and evoked muscle potential amplitudes (EMPA) were used to assess nerve function. Of the 49 transplanted diabetic animals, 40 had permanent functional allograft of either intraportal pancreatic whole islets (PWI) or intracerebral pancreatic endocrine cells (PEC). Normal MNCV and EMPA values (47.65 +/- 2.03; 5.22 +/- 0.43) were found among the recipients of intracerebral transplantation of PEC. The MNCV and EMPA were 43.30 +/- 2.59 and 4.49 +/- 0.53 respectively, in recipient rats with successful intraportal whole islet transplant. The nine animals with rejected whole islet allografts yielded MNCV and EMPA values (38.90 +/- 2.73; 3.87 +/- 0.59) comparable to the diabetic control rats.

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