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P McShane

Publications and source records attributed to P McShane.

At least 37 records · Page 2Linked to original sources
PubMed1988

Exocrine contamination impairs implantation of pancreatic islets transplanted beneath the kidney capsule.

The effect of exocrine contamination on islets implanted under the kidney capsule has been studied by histological examination of pure or exocrine-contamination human, monkey, or rat islets transplanted to the kidney capsule of the nude rat, monkey, or rat, respectively. Exocrine contamination resulted in an appearance suggestive of impaired islet implantation, due to tissue necrosis and subsequent fibrosis. The effect of exocrine contamination was examined quantitatively in a rat islet isograft model in which handpicked DA rat islets were transplanted under the kidney capsule of normal DA rats. The islets were either pure or deliberately recontaminated with exocrine tissue (50 or 90% contamination). Four hundred pure islets were placed under one kidney capsule and 400 islets (of similar size and from the same islet preparation) were contaminated and then placed under the contralateral kidney capsule. After 2 weeks the kidneys were removed and extracted for insulin content. The insulin content of kidneys bearing islets contaminated by either 50 or 90% exocrine tissue was significantly reduced when compared to the contralateral kidney bearing pure islets. These findings support the view that exocrine contamination of islets resulted in impaired islet implantation when transplanted to a confined site such as the kidney subcapsule.

Animals↗
PubMed1987

Survival of cryopreserved isolated adult human pancreatic islets of Langerhans.

Human islets of Langerhans were isolated from the pancreata of 13 adult organ donors, cultured for 24 h, cryopreserved, stored in liquid nitrogen at -196 degrees C for 6-88 days, thawed, and then cultured again. The number of islets recovered after this procedure was 80% of that present at the beginning. The viability of cultured/cryopreserved islets was then compared with that of islets from the same donor cultured for 24 hr, and was assessed by supravital staining, insulin response to glucose, and survival after implantation under the kidney capsule of nude rats. Supravital staining showed more nonviable cells in cryopreserved islets than in their cultured counterparts. Significant response to glucose was seen before and after cryopreservation in 2 of 4 sets of islets. Xenografts of 200 cultured islets (from 13 donors) were implanted in 15 nude rats under the kidney capsule, and a further 15 rats had cryopreserved islets (from the same 13 donors) similarly implanted beneath the kidney capsule. Two weeks later tissue was visible at the site of implantation in all 30 rats. Histological examination of both groups showed the tissue to have the morphology of islets, confirmed by immunohistochemical chemical localization of insulin. The insulin content of kidneys bearing 200 cultured islets was 7.88 +/- 1.6 mU (n = 13) versus 6.84 +/- 1.43 mU (n = 13) for kidneys bearing cryopreserved islets. Thus this technique for cryopreservation of isolated adult human islets enables a high recovery of endocrine tissue that survives after transplantation to nude rats, but some evidence of damage was apparent from insulin secretion studies and electron-microscopic studies.

Animals↗
PubMed1986

Successful autotransplantation of isolated islets of Langerhans in the cynomolgus monkey.

A recently described method for isolation of islets of Langerhans from the human pancreas has been adapted to the cynomolgus monkey pancreas. The mean yield of islets obtained from 13 monkey pancreata was 1319 islets per gram of pancreatic tissue (range 533-1800) and the usual purity of the preparation varied from 5 to 15 per cent islet tissue. Twelve cynomolgus monkeys underwent total pancreatectomy, preparation of islets from the excised pancreas and autotransplantation to either the spleen or the liver. Three animals received no transplant and became immediately diabetic, surviving 4-8 days. Four animals became normoglycaemic after intrasplenic islet transplantation, and survived 6 weeks, at which time splenectomy was performed with immediate onset of diabetes. Splenic vein insulin sampling confirmed the spleen as the source of insulin, and histological examination showed implanted islet tissue in all cases. Five animals became normoglycaemic after intrahepatic islet implantation. Three animals subsequently became diabetic at 4 and 5 months and two animals still have functioning grafts, the longest function being 9 months. These results suggest that in the cynomolgus monkey sufficient islets can be extracted from a single donor pancreas to reverse diabetes.

Animals↗
PubMed1986

The use of spleen transplantation and cyclosporine treatment to induce unresponsiveness to pancreatic islet transplantation in rats.

One way of achieving permanent survival of allografted islets in the rat has been to first transplant a kidney of the same strain as the islets and induce acceptance of the kidney using cyclosporin A treatment. Rats bearing long-surviving renal allografts will then accept islets of the same strain without further immunosuppression. Such an approach may be effective for combined renal and islet grafting, but transplantation of the kidney as well as islets may not always be desirable, and the question arises as to whether another organ could be used to achieve the same effect. Auxiliary spleen transplants were performed from LEW to DA rats, followed by cyclosporine 10 mg/kg for 14 days. Twelve rats with long-surviving grafts were then made diabetic with streptozotocin and given LEW islets placed under the kidney capsule, 6 rats being given a further course of cyclosporine 10 mg/kg for 7 days after islet transplantation. Rats that did not reject their islets then underwent removal of the spleen transplant, and if this did not result in rejection islet function was proven by removal of the kidney bearing the islets. The results show that spleen allograft rejection can be prevented by cyclosporine treatment and that 50% of animals with long-surviving spleen allografts will accept subsequent islet allografts from rats of the same donor strain. The acceptance of islet allografts can be increased to 100% by a further short course of cyclosporine treatment. It is concluded that spleen allografts can be used to produce unresponsiveness to islets in rats.

Animals↗
PubMed1986

The effect of hyperglycemia on isolated rodent islets transplanted to the kidney capsule site.

The effect of hyperglycemia on transplanted rat pancreatic islets was studied using a new technique for transplanting a defined number of islets in a blood clot. Normal or streptozotocin-diabetic DA rats were given 400 DA islets under the left kidney capsule (a number shown to be insufficient to reverse diabetes). After 2 weeks the diabetic rats were given a further 1000 islets under the right kidney capsule to reverse diabetes. Kidneys from both groups were examined at 2 weeks after the initial islet implant and at 3 months for both gross and histological appearance and for insulin content. After 2 weeks left kidneys from nondiabetic rats showed abundant islet tissue, with an insulin content of 116 (+/- 14 SEM) milliunits, compared to 1 +/- 0.5 milliunits in the right kidney. Kidneys from diabetic rats showed no islets recognizable grossly. Histological examination showed vacuolated tissue scarcely recognizable as islet tissue, and the insulin content of the left kidney was reduced to 18 +/- 5 milliunits. However, 3 months after reversal of diabetes by transplantation of 1000 islets to the right kidney, histologically "normal" islet tissue was again visible on the left kidney, and the insulin content was 160 +/- 36 milliunits. Islets left in normal animals for 3 months contained 195 +/- 50 milliunits. These experiments show that islets implanted beneath the kidney capsule in diabetic rats are not destroyed by two weeks hyperglycemia. This suggests that protection of islets after implantation by insulin treatment is unnecessary, even in the presence of a persistently raised blood sugar.

Animals↗
PubMed1985

The efficacy of internal iliac artery ligation in obstetric hemorrhage.

During 1966 to 1982, 18 patients with severe obstetric hemorrhage underwent hypogastric artery ligation at our institution. Eight of 14 patients or 57 per cent (excluding three pregnancies which were terminated and a planned cesarean hysterectomy) had failed hypogastric artery ligations necessitating hysterectomy. Placenta accreta accounted for six patients of whom three required a hysterectomy. Uterine laceration was the second largest cause of hemorrhage in five patients, all of whom required a hysterectomy after hypogastric artery ligation failed. Hypogastric artery ligation does have a specific role in the management of obstetric hemorrhage, but it is not without substantial risk of failure. The obstetrician should carefully weigh whether or not the patient can undergo a more conservative procedure at the expense of a delay in the definitive treatment of hemorrhage. The instances presented herein should aid the clinician in deciding what is appropriate management for acute obstetric hemorrhage.

Acute Disease↗
PubMed1984

Isolated pancreatic islet allografts in rats rendered immunologically unresponsive to renal allografts. The effect of the site of transplantation.

Long-surviving Lewis (RT-1(1)) renal allografts (LS-LEW) were induced in 20 DA (RT-1a) rats by 14-day treatment with cyclosporine . All were made diabetic 100 days after transplantation using streptozotocin; 7 LS-LEW were untreated and all remained diabetic; 5 LS-LEW were given Lewis islets beneath the kidney capsule without further immunosuppression. Prolonged graft survival (greater than 100 days) was seen in 4 rats. Lewis islets were given into the portal vein in 5 LS-LEW. Prolonged graft survival was seen in 4 rats. Third-party BN islets were given beneath the kidney capsule in 3 LS-LEW; these islets were rejected in less than 9 days. In contrast Lewis islets transplanted into untreated diabetic DA rats beneath the renal capsule or into the portal vein survived for a mean of 8.3 days and 4 days, respectively. In a separate experiment long-surviving Lewis renal allografts were induced in 7 PVG rats (LS-PVG) by cyclosporine treatment. These animals were made diabetic 100 days after transplantation and then were given Lewis islets under the renal capsule of the transplant kidney. Prolonged islet graft survival was seen in 6 rats, and 5 diabetic PVG rats given Lewis islets beneath the renal capsule rejected the islets within 8 days. Thus, once a recipient rat has accepted a renal allograft under the influence of cyclosporine treatment, it will accept permanently an islet allograft of the same strain as the kidney. This effect applies to both strain combinations tested, is not influenced by the site of islet implantation, and is specific for islets of the same strain as the renal allograft.

Animals↗
PubMed1984

A method for isolation of islets of Langerhans from the human pancreas.

A method has been developed for the isolation of islets of Langerhans from the human pancreas. The average number of islets isolated was 1011 islets per gram of pancreas (SD 475, range 752-2111), and the purity of the preparation as defined by histologic examination and specific staining for insulin varied from 10% to 40%. Islet structure was well preserved and the islets were shown to be viable by supravital staining, demonstration of insulin response to glucose, and by transplantation of isolated islets beneath the renal capsule of nude mice. The essential features of this technique for isolation of human islets include injection of a high concentration of collagenase (6 mg/ml) into the pancreatic duct under pressure, followed by a short incubation (23 min) at 39 degrees C. The gland is then dispersed by a process of teasing and shaking, and the islets are separated by a two-stage process of filtration on a nylon mesh to remove the larger islets and centrifugation on a preformed Ficoll density gradient to separate the small islets.

Animals↗
PubMed1984

Observations on rat collagenase-separated islets and long-term composite islet allografts.

Collagenase digest preparations of isolated rat islets and long-surviving allogeneic rat islets implanted beneath the kidney capsule of a composite kidney and islet allograft have been studied immunocytochemically and by electron microscopy. The four main endocrine cell types were identified in the collagenase preparations with minimal evidence of cell damage. In contrast, there were only granulated B cells in the composite grafts and amongst the granules of these cells there was pleomorphism. The granule appearances may support previous suggestions that paracrine control of insulin secretion is lacking in these composite grafts.

Animals↗
PubMed1983

The long-term allografted rat islet. A histologic and immunohistologic study.

Long-term survival of islet allografts was achieved with an experimental model in the rat by the transplantation of islet/kidney composite grafts. Morphologic studies of these grafts incorporating immunocytochemistry have been made. Ther was minimal evidence of rejection of the transplanted islet tissue, which was composed almost entirely of insulin-containing cells. There were a few glucagon-containing cells, but pancreatic polypeptide-labeled and somatostatin-labeled cells were rarely seen. The endocrine cells were in different proportions and had no discernible relationship to one another, in contrast to those in nontransplanted islets. For successful clinical transplantation, it may be necessary to maintain normal relationships between endocrine cells.

Animals↗
PubMed1983

The use of the dye neutral red as a specific, non-toxic, intra-vital stain of islets of Langerhans.

The development of improved methods of islet isolation from the pancreas is hampered by difficulty in identification of islets. A method described by Bensley in 1911 uses neutral red to stain the islets selectively. In the present study the method has been simplified and selective staining of islets in the rat, dog and pig demonstrated by use of light and electron microscopy. Staining of islets with neutral red does not appear to affect their viability as judged by insulin secretion and transplantation in rats.

Animals↗
PubMed1982

Glucose and insulin changes following a renoportal shunt in streptozotocin diabetic rats with pancreatic islet isografts under the kidney capsule.

The effect on glucose metabolism of altering the site of the venous drainage of an isograft of isolated adult islets implanted beneath the renal capsule, from the systemic circulation to the portal circulation was determined in streptozotocin-induced diabetic rats. Reversal of diabetes was accomplished by the transplantation of 1000-1200 isolated islets beneath the left kidney capsule. The rate of fall of the glucose concentration (as expressed by the K value) was found to be significantly decreased in transplanted animals (1.7 +/- 0.5%/min; mean +/- SD) compared with normal animals (2.4 +/- 0.5%/min). Draining the left renal vein into the portal circulation restored the K value to that of normal animals (2.5 +/- 0.4%). However the fasting glucose concentration was significantly higher and the basal insulin levels lower in both normal and transplanted rats with a renoportal shunt.

Animals↗