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Biomedical subjects

H J Hahn

Publications and source records attributed to H J Hahn.

At least 91 records · Page 5Linked to original sources
PubMed1988

[Immunocytochemical studies of the development of basal cell types of human islet organs].

The investigations are carried out in 19 human fetal pancreases. The detection of the 4 islet hormones insulin, glucagon, somatostatin and PP ist carried out in PAP-technique. The parts of these 4 types of islet cells are estimated quantitatively. In the 10th to 15th week of development insulin-producing B-cells are present. Moreover glucagon-, somatostatin- and PP-cells in the islet organ are present. In the group of 16th to 20th week of gestation insulin-, glucagon- and somatostatin-cells are increased compared to the first group. PP-cells are not altered. The increase of 3 types of islet cells is a result of fetal development.

Glucagon↗
PubMed1988

Phases in the early development of the human islet organ.

The study included morphometric examination and biochemical investigation of 41 human pancreata taken from 14th to 26th weeks of fetal development. 3 phases of development were observed. Phase I (weeks 14 to 16) is characterized by the presence of mainly islet buds. They were originated from the ducts and are vascularized during week 16. During phase II (17th to 20th weeks) the islet buds were detached from the ducts and they formed new mantled islets with the B cells in the centre. Non-B cells are situated on the periphery around the insulin producing cells. Phase III lasts from week 21 to week 26. During this phase B cells and non-B cells become more irregularly positioned within the islet, a cytology, which is similar approximating that of as also found in adult human islets. The changes of islet structure during pancreatic development are accompanied by other typical phenomena: Islet size increases during phases I and II, but decreases again during phase III. The proportion of isolated B cells outside of the islets varies during this stage of fetal development, but they generally account for about 15% of the total islet organ. This should be taken into account when assessing the islet function De Pablo et al. (1985) on a morphological basis.

Gestational Age↗
PubMed1988

Syngeneic transplantation of thyroid tissue encapsulated in a cellulose sulphate membrane.

A new, simple encapsulation method, the precipitation of a polyelectrolyte complex membrane of cellulose sulphate and poly(dimethyldiallylammoniumchloride) was investigated in syngeneic thyroid transplantation. Half a thyroid gland was placed beneath the kidney capsule either after being encapsulated or as a non-encapsulated control graft. In normo-thyroid as well as hypothyroid recipients, the grafted tissue was viable for up to 12 weeks. Furthermore, the hypothyroid state, which was characterized by a markedly diminished 125iodine incorporation into the thyroid, no body weight gain and undetectable serum thyroxin concentrations, was compensated by the grafted tissue. The encapsulated grafts showed lower iodine incorporation, T4 secretion and body weight gain when compared with non-encapsulated control grafts. This may be due to a partial restriction of TSH by the capsule membrane. It was concluded that the cellulose sulphate membrane is biocompatible and enables the functional survival of syngeneic grafted tissue.

Animals↗
PubMed1988

[Evaluation of retard drug forms with special reference to their therapeutic aspects].

The useful development and application of controlled-release dosage forms is an important possibility to improve the pharmacotherapy of many diseases. However, according to the present social conditions of reproduction the introduction of a new drug has to be directed not only to a high therapeutic benefit but also to an increased social efficiency i.e., to an improvement of cost-benefit-relation. In the present study, therefore, the effect of using controlled-release dosage forms on the development of social efficiency is discussed. Basing on a comprehensive estimation of the therapeutic efficiency (therapeutic advantages and disadvantages) of controlled-release dosage forms the criteria of cost and benefit being of importance for a complex evaluation of efficiency are described.

Delayed-Action Preparations↗
PubMed1987

Curing BB rats of freshly manifested diabetes by short-term treatment with a combination of a monoclonal anti-interleukin 2 receptor antibody and a subtherapeutic dose of cyclosporin A.

The BioBreeding (BB) rat develops spontaneously a syndrome resembling human type I diabetes mellitus. The short-term treatment of newly diagnosed diabetic BB rats with the anti-interleukin 2 receptor (IL 2R) monoclonal antibody ART-18 in combination with a subtherapeutic dose of cyclosporin A for 10 days, a treatment shown previously to eliminate specifically antigen-activated IL2R+ T lymphocytes by sparing suppressor cells, resulted in normoglycemia in 70% of the animals, the maintenance of B cell volume density and an increase in pancreatic insulin content. Moreover, the glucose tolerance of successfully treated animals was not significantly different from that of normoglycemic BB rats during the whole observation period (up to 120 days after the end of the therapy). This is the first report on successful treatment of a spontaneous autoimmune disease by a short-term and specific immunosuppressive regimen with limited side effects.

Animals↗
PubMed1987

Prolongation of rat pancreatic islet allograft survival by treatment of recipient rats with monoclonal anti-interleukin-2 receptor antibody and cyclosporin.

Since interleukin-2-receptor expressing cells play a role in allograft rejection, we investigated the effect of anti-interleukin-2 receptor monoclonal antibody treatment on graft survival of allografted pancreatic islets. When pancreatic islets obtained from Lewis A-rats (haplotype RT1a) were grafted under the kidney capsules of streptozotocin-diabetic Lewis rats (haplotype RT1u), the recipients relapsed into hyperglycaemia within 11 days (7 +/- 1 days). Treatment of the recipient rats with low-dose cyclosporin (1.5 mg/kg body weight) had no effect on allograft survival (9 +/- 1 days). The application of anti-interleukin-2 receptor monoclonal antibody (1 mg/kg body weight) for 10 days resulted in a prolongation of allograft survival (42.5 +/- 15.3, p less than 0.01). In 3 out of 11 animals a permanent normoglycaemia (greater than 120 days) associated with glucose intolerance was observed. When the recipients were treated for 10 days with cyclosporin and anti-interleukin-2 receptor monoclonal antibody, the allograft survival was also prolonged (45.1 +/- 14.6, p less than 0.01); again 3 out of 11 animals remained permanently normoglycaemic while exhibiting a normal glucose tolerance.

Animals↗
PubMed1987

Induction of a diabetes-like syndrome by cyclosporine in Wistar rats and its reversibility after drug withdrawal.

Cyclosporin A exerts dose- and time-related toxic effects on pancreatic B-cells. We investigated the reversibility of Cyclosporin A-induced alterations on glucose tolerance and pancreatic insulin content in Wistar rats either still normoglycaemic or animals being hyperglycaemic after different treatment periods. Both groups of animals either formerly normoglycaemic but glucose intolerant or hyperglycaemic normalized glucose intolerance, glycaemia and reenhanced pancreatic insulin content. This demonstrates that also hyperglycaemic animals are able to recover spontaneously from a diabetes-like state.

Animals↗
PubMed1987

Prevention of complement-mediated cytotoxicity against rat islets by encapsulation in a cellulose sulphate membrane.

The immuno-isolation by semipermeable membranes should prevent the immunological destruction of the transplanted tissue. The polyelectrolyte complex membrane from cellulose sulphate and poly(dimethyldiallylammoniumchloride), which does not alter the viability of the encapsulated rat islets, can prevent complement-mediated cytotoxicity. The 51Cr release from prelabelled islets, which was induced by either unspecific cytotoxicity of rabbit sera against the rat islets or by an anti-MHC rat serum in presence of complement, was prevented. The diffusion of immunoglobulins as well as of factors of the complement system was inhibited by encapsulation. The capsule membrane also prevents the beta-cell destruction in cytotoxic sera from newly diagnosed type-I diabetics measured as insulin leakage after blocking the active hormone secretion. In conclusion, the cellulose sulphate membrane seems to be useful for the transplantation of encapsulated islets.

Animals↗
PubMed1987

Tissue cultivation as a method for preservation of human foetal islet parenchyma--a correlated biochemical, immunohistochemical and morphometric investigation.

Tissue culture of human foetal pancreas slices, obtained at a gestational age between 10 and 19 weeks, as a method of preservation and to pool the material before transplantation was investigated. Before and after 2 weeks of culture the pancreatic insulin content, the insulin secretion in response to glucose and isobutylmethylxanthin (IBMX) as well as the protein biosynthesis were measured. In addition, the distribution of the insulin immunoreactive cells was examined, as well as their relative volume density. After 2 weeks' culture an increase of the basal insulin secretion was observed; this was probably due to the glucose content (10 mmol/l) in the culture medium. Neither the stimulated insulin secretion, nor the protein biosynthesis, the insulin content, and the B-cell volume were altered by the used culture conditions. It was concluded that tissue culture is a suitable method to preserve human foetal pancreas slices before transplantation.

Culture Techniques↗
PubMed1987

[In vitro studies of amniotic fluid and intrauterine growth retardation].

Until now the intrauterine growth retardation remains as an insufficiently solved problem. The 3H-thymidine incorporation into the DNA of the isolated islets of Langerhans of neonatal Lewis rats was used as a marker for cell dividing activity in vitro. There was no inhibition effect on the 3H-thymidine incorporation in the presence of amniotic fluid from pregnancies with intrauterine growth retardation compared to those of normal pregnancies.

Amniotic Fluid↗
PubMed1987

Cytotoxic activity of sera from diabetic BB rats against BB rat islet--a functional study.

[3H] leucine incorporation into islet proteins, insulin secretion, hormone content (insulin, glucagon) and DNA synthesis were measured in cultured BB rat islets in a study to compare the effect of freshly prepared BB rat serum obtained from non-diabetic and newly diagnosed diabetic BB rats on islet functions. After exposure of isolated BB rat islet to a mixture of tissue culture medium and BB rat serum (1:1) for 24 hr, islet lysis was induced by 40% of the diabetic BB rat sera whereas the remaining 60% of diabetic BB rat sera tested did not influence islet functions as evidenced by insulin net production, glucose-induced insulin release and DNA synthesis measured in a subsequent culture period in TCM 199, 10 mmol/l glucose supplemented with 10% neonatal calf serum or short-term incubations. After exposure of islets to sera with anti-islet cytotoxicity the majority of islet cells were destroyed as indicated by a drastically reduced [3H] leucine incorporation into islet proteins and by a diminution of hormone and DNA content of islets. This toxicity against islets was overcome by heat treatment (58 degrees C, 30 min) of sera. The results indicate that heat-labile components in certain diabetic sera of BB rats can lyse the majority of islet cells in BB rat islets within 24 hr. Our assay may help to dissociate humoral and cellular components which cause the injury of beta cells and the onset of diabetes in BB rats.

Animals↗
PubMed1986

Reversibility of the acute toxic effect of cyclosporin A on pancreatic B cells of Wistar rats.

This study investigated if and to what extent the acute toxic effect of Cyclosporin A on pancreatic Wistar rat B cells is reversible. After 2 weeks of treatment rats developed marked glucose intolerance accompanied by reduced pancreatic insulin content due to a loss of B cells, diminished islet DNA synthesis and decreased B-cell insulin content. Cyclosporin A had accumulated in the pancreas. Three weeks after withdrawal of Cyclosporin A, pancreatic tissue concentrations of Cyclosporin A were still 100 times larger than in serum. Glucose tolerance, however, had already improved, associated with an increase of B-cell insulin content and apparent islet replication, and the insulin response of isolated islets was reduced. Five weeks after the withdrawal of Cyclosporin A, glucose tolerance was normal, but pancreatic insulin content and relative B-cell volume were still diminished in comparison to vehicle-treated controls. Eight weeks after withdrawal, the morphometric parameters had also been normalized. The results suggest that the loss of pancreatic B cells is caused by a toxic destruction, possibly combined with an apparent decrease of replicatory activity. The acute toxic effects of Cyclosporin A in pancreatic B cells are stepwise reversible.

1-Methyl-3-isobutylxanthine↗
PubMed1986

The action of cyclosporin A on the endocrine pancreas in vitro--functional and morphological studies.

We investigated the effect of Cyclosporin A (100 ng/ml - 12000 ng/ml) on functional parameters of the endocrine pancreas in vitro. The insulin secretion of isolated islets in response to a variety of secretory stimulators is characterized by minimal alteration occasionally observed in the presence of very high Cyclosporin A concentrations. Cyclosporin A did not alter the glucose-induced biphasic insulin secretion, nor the arginine-stimulated glucagon secretion of the perfused rat pancreas. Exposure of isolated islets to 2000 ng Cyclosporin A/ml for 3 weeks resulted in a minimal decrease of insulin content and a marked reduction of glucagon content, which were not accompanied by drastic alterations of insulin secretion. Scanning electron micrographs of these Cyclosporin A-treated islets did not differ from cultured control islets. The results let us assume that Cyclosporin A exerts no toxic effects on the endocrine pancreas in vitro, when exposed to concentrations greater than or equal to 2000 ng/ml.

Animals↗
PubMed1986

The long-term culture of encapsulated pancreatic islets.

A new encapsulation technique, the formation of a polyelectrolyte complex membrane from sodium cellulose sulphate and a polycationic solution (polydimethyldiallylammoniumchloride) can be used for culturing pancreatic islets. After 5 weeks of culture, such encapsulated islets were morphologically well preserved, and parameters of cell viability and functionality such as DNA content and DNA synthesis, insulin content and stimulated insulin release were not different between the encapsulated and non-encapsulated control islets. A lower insulin secretion into the medium of the encapsulated islets during the first 3 weeks of culture can probably be explained by the capsule diameter (4-5 mm) and should be improved using microcapsules with a diameter of less than 1 mm.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Toxic effects of cyclosporine on the endocrine pancreas of Wistar rats.

The widely used immunosuppressive drug cyclosporine exerts toxic effects on various parenchymal organs including the liver and kidney. This study was performed with the aim of testing whether cyclosporine also affects the endocrine pancreas. Daily cyclosporine doses of 50 mg/kg body weight over 3 weeks in rats enhanced the serum bilirubin and creatinine concentrations, led to light-microscopic destruction in the liver and kidneys, and resulted in the development of an impaired glucose tolerance--and, later on, of hyperglycemia. The pancreatic insulin content decreased to 33% of values observed in vehicle-treated controls, which can be ascribed to a 50% decrease of beta-cell volume and a slightly smaller reduction of islet insulin content. The reduction of the cyclosporine dose to 15 mg/kg body weight daily, which also reduced the popliteal lymph node weight gain after allogeneic stimulation, was not accompanied by serochemical or morphological alterations of livers or kidneys in the rats when treated for 3 weeks. However, the animals had already developed an impaired glucose tolerance, accompanied by a decrease in pancreatic insulin content (to 50% that of controls), a decrease of islet insulin content (to 70%) and a reduced pancreatic beta cell volume (to 72%). The findings let us conclude that pancreatic beta cells are sensitive to toxic effects of cyclosporine in vivo. We suggest that the measurement of glucose tolerance, as a sensitive parameter of a toxic cyclosporine action, should be included in the monitoring of grafted patients under cyclosporine treatment.

Animals↗