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Biomedical subjects

B J Hering

Publications and source records attributed to B J Hering.

At least 19 recordsLinked to original sources
PubMed1996

Islet cell antibodies and glutamic acid decarboxylase antibodies in patients with insulin-dependent diabetes mellitus undergoing kidney and islet-after-kidney transplantation.

The humoral immune response to islet autoantigens, here defined by the presence of islet cell antibodies (ICA) and glutamic acid decarboxylase (GAD 65) antibodies, was studied in patients with long-term insulin-dependent diabetes mellitus (IDDM) receiving immunosuppressive therapy following kidney and islet-after-kidney transplantation. In a cross-sectional study of 30 kidney-grafted, long-term IDDM patients and 30 matched, nontransplanted IDDM controls, we observed a significant (P<0.05) decrease in ICA positivity by standard immunosuppressive therapy, but not in frequency or index levels of GAD 65 antibodies. Because of this intriguing finding, we investigated, in a pilot study on seven islet-after-kidney transplant recipients, the time course of frequency and levels of ICAs and GAD 65 antibodies relative to islet graft function. Stable islet graft function was seen in the patients with low GAD 65 antibody index levels, whereas rapid islet graft failure occurred in a patient with high GAD 65 antibody index levels prior to transplantation. In addition, GAD 65 autoimmunity reoccurred in one pretransplant antibody-negative patient 2 months after graft failure was noted. In conclusion, these observations suggest that beta-cell autoimmunity directed to GAD 65 can persist despite immunosuppressive therapy and may adversely affect islet graft function, possibly indicating disease recurrence as a major threat to successful clinical islet transplantation.

Adult↗
PubMed1996

Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus.

The intraportal injection of human pancreatic islets has been indicated as a possible alternative to the pancreas transplant in insulin-dependent diabetic patients. Aim of the present work was to study the effect of intraportal injection of purified human islets on: (a) the basal hepatic glucose production; (b) the whole body glucose homeostasis and insulin action; and (c) the regulation of insulin secretion in insulin-dependent diabetes mellitus patients bearing a kidney transplant. 15 recipients of purified islets from cadaver donors (intraportal injection) were studied by means of the infusion of labeled glucose to quantify the hepatic glucose production. Islet transplanted patients were subdivided in two groups based on graft function and underwent: (a) a 120-min euglycemic insulin infusion (1 mU/kg/min) to assess insulin action; (b) a 120-min glucose infusion (+75 mg/di) to study the pattern of insulin secretion. Seven patients with chronic uveitis on the same immunosuppressive therapy as grafted patients, twelve healthy volunteers, and seven insulin-dependent diabetic patients with combined pancreas and kidney transplantation were also studied as control groups. Islet transplanted patients have: (a) a higher basal hepatic glucose production (HGP: 5.1 +/- 1.4 mg/kg/ min; P < 0.05 with respect to all other groups) if without graft function, and a normal HGP (2.4 +/- 0.2 mg/kg/min) with a functioning graft; (b) a defective tissue glucose disposal (3.9 +/- 0.5 mg/kg/min in patients without islet function and 5.3 +/- 0.4 mg/kg/min in patients with islet function) with respect to normals (P < 0.01 for both comparisons); (c) a blunted first phase insulin peak and a similar second phase secretion with respect to controls. In conclusion, in spite of the persistence of an abnormal pattern of insulin secretion, successful intraportal islet graft normalizes the basal HGP and improves total tissue glucose disposal in insulin-dependent diabetes mellitus.

Adult↗
PubMed1995

Islet isolation from the pancreas of large mammals and humans: 10 years of experience.

Despite experience, that has been obtained in the field of islet isolation in large mammals for about the past 20 years, allo- and autotransplantation of both human and porcine islets are still not routine procedures. The reasons for islet isolation and purification associated problems, which prevent a continuous isolation success and regular islet transplantation, can be categorized to variables related to 1) pancreas donor; 2) pancreas procurement; 3) isolation-techniques and 4) purification techniques. The development of porcine and human islet isolation was carried out by the authors since 1986. During this period several techniques for the isolation and purification of human and porcine islets were compared with regard to their influence on islet isolation outcome, integrity of islet morphology, islet in-vitro and in-vivo function: sequential vs continuous digestion-filtration, counterflow elutriation vs neutral density separation, conventional density gradient centrifugation vs Cobe cell separation and discontinuous vs continuous gradient purification. Furthermore, we analysed the influence of donor factors and variables related to organ procurement on islet isolation success. From this experience we concluded that successful porcine islet isolation is possible if islets of adult donors are isolated utilizing the continuous digestion-filtration following distension with UW-solution prior to a neutral density gradient purification on a Cobe. Human islets can be successfully isolated by digestion-filtration and purified utilizing a continuous Ficoll-sodium-diatrizoate gradient on a Cobe when intact pancreata are harvested after a secondary pancreatic warm ischemia time < 20 min from adult donors > 30 years.

Adult↗
PubMed1995

Body mass index of pancreatic donors: a decisive factor for human islet isolation.

Despite improvements in islet isolation techniques, islet transplantation remains unpredictable as a method for reliably rendering human type I diabetic recipients normoglycemic. Advances in immunosuppression to prevent primary nonfunction, to promote engraftment and to prevent rejection should improve success rates. However, factors influencing the isolation process remain incompletely defined. During our experience, the donor's nutritional status as well as other donor characteristics were noted to be associated with islet isolation success. Thus, in this study, we tried to clarify whether the body mass index of the human pancreatic donor affects islet isolation yield and viability. In lean donors we found significantly lower islet yields in comparison with normal and obese donors and a significantly lower islet viability compared to obese donors. Obese donor islets had a significantly higher insulin secretory capacity than lean and normal donor islets. In summary, islet yield and viability were improved selecting pancreata from obese donors associated with a BMI > 24 for islet preparation. We hypothesize that, on the one hand, the increased distribution of fat in pancreata of obese donors possibly can facilitate the release of islets during the collagenase digestion, and, on the other hand, pancreata of obese donors contain more islets than pancreata of lean donors. These data underline the decisive influence of the pancreas donor's body mass index on successful human islet isolation. The body mass index should be noted as a potential predictor of success of islet preparations.

Body Mass Index↗
PubMed1995

Different toxic effects of hydrogen peroxide, nitric oxide, and superoxide on human, pig, and rat islets of Langerhans.

Susceptibility of islet cells to damage by hydrogen peroxide, superoxide, and nitric oxide was determined on islets isolated from humans, pigs, and rats. Islets were incubated for 20 hr at 37 degrees C with different concentrations of hydrogen peroxide, hypoxanthine/xanthine oxidase, or nitroprusside sodium, respectively. Islet cell damage was then measured as trypan blue-uptake. Rat islets showed a higher sensitivity than human or pig islets to damage by reactive oxygen species or nitric oxide. These results indicate that pig islets may be a more suitable model than rat islets to study inflammatory islet cell damage in diabetes and clinical islet transplantation.

Animals↗
PubMed1995

Islet cell transplantation in diabetes mellitus--from bench to bedside.

Replacement of the patient's islets of Langerhans either by pancreas transplantation or by isolated islet transplantation is the only treatment of type I diabetes mellitus to achieve an insulin-independent, constant normoglycemic state. The expense for this benefit is the need for immunosuppressive treatment of the recipient with all its potential risks. Thus, indications for pancreas or islet transplantations at present exist almost exclusively in patients with end-stage renal disease who are waiting on dialysis for a kidney graft or in diabetics with an established kidney graft obliged to be immunosuppressed. Islet transplants possess significantly potential advantages over whole-gland transplants: it is a simple procedure with only small risk, if any; it offers the potential advantages of pre-transplant reduction of immunogenicity thus possibly obviating the need for continuous life-long recipient immunosuppression and it offers the future feasibility of transplanting heterologous (pig) islets. The effectiveness of this concept was demonstrated in animal experiments and may be successfully transferred into the clinical situation. In this case, the indications for islet transplantation may be extended to non-uremic type I diabetics including diabetic children. This group of patients is the ultimate target group for this most direct and appealing concept of treating type I diabetes. As of 1994, more than 200 adult islet allografts were reported to the International Islet Transplant Registry (ITR) at the Justus-Liebig-University, Giessen, Germany. A detailed analysis of 75 well-documented cases grafted between 1990 and 1993 revealed a one-year survival rate of the patients and islets of 95% and 28% (in terms of significant basal C-peptide secretion), respectively, and insulin independence was achieved in 11% of the cases after simultaneous islet-kidney (SIK) or islet-after-kidney (IAK) transplants. At present, there is no clinical data available and the follow-up studies of the posttransplant period are too short to draw any conclusions concerning the effects of islet transplants on diabetic secondary complications. Moreover, islet transplantation is still a clinical investigational procedure. Obviously, a number of fundamental steps will have to be taken before the appealing concept of transplanting adult pancreatic islets can attain clinical importance in the treatment of type I diabetic subjects. Islet cell transplantation has come the long way from animal experiments to successful clinical application, but, more research at the bench has to be performed before islet cell transplants will be successfully performed in non-uremic, non-kidney transplanted type I diabetic patients.

Animals↗
PubMed1995

The effects of glucagon-like peptide-I (GLP-I) on hormone secretion from isolated human pancreatic islets.

Glucagon-like peptide-I (GLP-I) is a potent incretin hormone that is now considered as a new therapeutic tool in the treatment of diabetes mellitus. In this study we characterized the effects of GLP-I on peptide hormone release from isolated human pancreatic islets. GLP-I stimulated insulin release in the presence of 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 166%; 10 mM glucose + 10 nM GLP-I, 222%) but had only a weak insulinotropic effect (128%) at 2.8 mM glucose. Glucagon release was inhibited by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 72%) and by 10 nM GLP-I at 2.8 mM glucose (67%). Somatostatin secretion was increased by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 166%). GLP-I stimulated somatostatin release in the presence of 2.8 mM glucose (172%). Pancreatic polypeptide (PP) secretion was enhanced by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 236%). GLP-I induced PP release only in the presence of 2.8 mM glucose (184%).

Culture Techniques↗
PubMed1995

[Combined liver-islet transplantation after epigastric exenteration in carcinoma of Vater's ampulla].

A 44 year old female underwent an upper abdominal exenteration because of an adenocarcinoma of the pancreas with liver metastases (T1 N1 M1). Reconstruction was performed by orthotopic liver transplantation and intraportal islet transplantation. Due to initial non function of the first liver graft, a second liver transplantation was performed. Thereafter, the patient received 375,000 islet equivalents of the primary liver donor in addition to 295,400 islet equivalents of another donor. Six months postoperatively, the patient is off insulin except irregular injections of 4-6 units of insulin to protect her from hyperglycemia after lunch. CT scans of the liver do not show any signs of tumor recurrence. Upper abdominal exenteration with consecutive islet transplantation offers a good method of reconstruction after radical surgery in the upper abdomen. The oncological aspects of the procedure have to be further investigated.

Adenocarcinoma↗