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Biomedical subjects

H J Hahn

Publications and source records attributed to H J Hahn.

At least 37 records · Page 2Linked to original sources

Intraportal transplantation of pancreatic islets into livers of diabetic rats. Reinnervation of islets and regulation of insulin secretion by the hepatic sympathetic nerves.

Two weeks after intraportal transplantation of 2,000 neonatal pancreatic islets, recipient rats completely recovered from streptozotocin-induced diabetes. The reversal of diabetes could be documented by the normalization of blood glucose levels, by a restored weight gain, by normal glucagon and insulin levels in blood, and by a disappearance of polyuria and polydipsia. The reversal remained stable for at least 9 months. This study determined whether intraportally transplanted pancreatic islets were reinnervated after transplantation and whether the secretion of insulin and glucagon from pancreatic islets might be modulated by the vegetative innervation of recipient livers. Predominantly catecholaminergic but also cholinergic nerve fibers were detected not only within the portal tracts around hepatic arteries, portal veins, and bile ducts, but also at the borderline of hepatocytes and beta-cells and in islet cell complexes between beta-cells. Corresponding electron micrographs showed beta-cells in close contact with axons of nonmyelinated nerve fibers. Isolated livers were single pass perfused via both the hepatic artery and the portal vein. An increase in glucose level from 5 to 14 mmol/l enhanced hepatic glucose uptake and increased insulin secretion from transplanted islets with a biphasic secretion profile but had no effect on glucagon output. Stimulation of the nerve plexus around the hepatic artery and the portal vein (7.5 Hz, 2 min), which activates primarily the sympathetic system, not only reduced glucose uptake and perfusion flow but also completely reversed the glucose-stimulated increase in insulin secretion. Nerve stimulation did not influence glucagon secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

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Cathepsin L immunoreactivity in the hypothalamus of normal, streptozotocin-diabetic and vasopressin-deficient Brattleboro rats.

The immunolocalization of cathepsin L in the hypothalamus of normal rats was compared with the distribution of the enzyme in streptozotocin-treated animals and in vasopressin-deficient rats (Brattleboro strain). In rats with a normal metabolic status the neurons of magnocellular nucl. supraopticus and paraventricularis stood out by intense immunostaining for cathepsin L. In rats suffering from an experimentally induced diabetes mellitus and in homozygous Brattleboro rats we observed a strong reduction in enzyme immunoreactivity in these nuclei. Since cathepsin L is capable of splitting certain hypothalamic neuropeptides that are changed in diabetic animals, a role of the enzyme in the metabolism of these peptides is imaginable. Decrease in immunoreactive cathepsin L in vasopressin-deficient rats points to a possible involvement of the enzyme in the control of fluid homeostasis.

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Lack of disease recurrence in diabetic BB/Pfd rats after syngeneic islet transplantation.

Restimulation of autoreactivity in two different BB rat sublines of the same origin (Ottawa, Canada) was investigated by syngeneic islet transplantation into diabetic animals. Despite identical methods and conditions recurrence of hyperglycaemia was observed in BB/OK rats (Karlsburg, Germany) but not in BB/Pfd rats (Leuven, Belgium). Pancreatic morphology at the time of transplantation revealed significant differences in islet volume density and the degree of insulitis. Additionally, marked differences in the phenotypical composition of cells infiltrating the islets were observed. A loss of autoimmune memory in BB/Pfd rats is discussed as a probable reason for the lack of disease recurrence in those animals.

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[How frequent is the diagnosis of GI metastasis in an endoscopic patient sample in general internal medicine clinics> Results of a questionnaire survey of 34 medical clinics].

With the aim of analysing the frequency of gastrointestinal (GI) metastases identified by endoscopic procedures, a survey was conducted by questionnaire, which was completed by 34 of 127 medical departments. Peritoneal carcinosis and direct tumor extension were disregarded. One GI metastasis (duodenum) was verified among 3477 upper GI tract endoscopies. Primary site was cutaneous melanoma. In another case metastatic origin is discussed (esophagus). Considering the average frequency of 102 upper GI tract endoscopies performed by the collaborating centers, one case of gastroduodenal metastasis could be expected every 17 (34) months in these institutions. 1634 examinations of the colon and rectum did not reveal any metastatic tumor growth. A longterm study is planned to provide further statistically reliable prevalence data.

Aged↗

Transplantation of allogeneic fetal pancreases combined from MHC-different donor strains does not change rejection of the graft.

A number of 17.5- to 18.5-day-old fetal pancreases were grafted under the kidney capsule of streptozotocin-diabetic rats. Eight syngeneically grafted glands were sufficient to reverse the diabetes of the recipients within 4 weeks when the recipient rats were treated with insulin for 18 days after transplantation. Eight allogeneic fetal pancreases obtained from one donor strain were rejected after transplantation and the recipients relapsed into hyperglycemia immediately after insulin withdrawal. Eight allogeneic fetal pancreases obtained from eight MHC-different donor strains were also rejected and the recipients relapsed into hyperglycemia after insulin withdrawal. Using fetal pancreases as tissue sources, the combination of the allogeneic graft from different donor strains was not sufficient to prolong the survival time of the grafted tissue.

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Granular cell tumor in differential diagnosis of tumors of the breast. The role of fine needle aspiration cytology.

The granular cell tumor (GCT) represents a rare but important lesion in the differential diagnosis of breast tumors. Since this generally benign tumor may be misdiagnosed as malignant in clinical investigation, mammography, sonography, and even in frozen sections, a preoperative diagnosis is of utmost importance. Two cases illustrate that fine needle aspiration cytology (FNAC) may be the method of choice in achieving a correct preoperative diagnosis. The histogenesis of GCT is examined by means of immunohistochemical stainings. The results confirm that this tumor arises from the peripheral nerve tissue. Most likely the Schwann cells and not the nerve cells constitute the origin of GCT.

Adult↗

The effect of serum concentrations and sources on DNA synthesis and insulin secretion of cultured islets.

We investigated the effect of different sera, as newborn calf serum, fetal calf serum, rat serum and human serum at various concentrations on biofunctions of cultured pancreatic islets. Islets isolated from newborn LEW. 1 W rats were maintained at 37 degrees C in TCM 199 containing 10 mmol/l glucose and either 1%, 10% or 50% newborn calf serum (NCS), fetal calf serum (FCS), serum obtained from adult syngeneic rats (RS) or different batches of human serum (HS). While exposure of islets to increasing concentrations of NCS significantly inhibited the islet DNA synthesis as well as the glucose stimulated insulin secretion after 2, 4 and 8 days of culture, HS at different concentrations failed to inhibit both, the islet DNA synthesis and the secretory response to glucose at each time point investigated. The action of FCS, RS and 2 further batches of HS on islet DNA synthesis was analysed by short-term culture. The supplementation of the medium with 50% FCS and RS resulted in a marked decrease of H-thymidine incorporation into islet DNA similar to that observed with 50% NCS. In contrast, exposure of islets to different batches of HS never resulted in an inhibition of DNA synthesis. Moreover, the 50% concentration of HS 465 caused a significant stimulation of thymidine incorporation.

Animals↗

Induction of long-term survival of rat skin allografts by a novel, highly efficient anti-CD4 monoclonal antibody.

The new monoclonal antirat CD4 antibody RIB 5/2, which detects another epitope than those covered by W3/25 and MRC OX35, was tested for its immunosuppressive potency following skin allografting by using strain combinations with different genetic barriers in the MHC and genetic low- or high-responder background. High-dose and long-term therapy of the grafted rats led to a significant delay of the acute rejection (P < 0.01) in the strain combination Wistar Furth-to-BDX as well as in LEW1W-to-LEW1A. No significant prolongation of the mean allograft survival time was obtained for the high-responder rats (LEW1A-to-LEW1W). Cytofluorometric analysis revealed that RIB 5/2 exerts the immunosuppressive activity predominantly by modulation of the CD4 glycoprotein. Furthermore, the dependence of the humoral immune response against the mouse-globulins upon the administered protein quantity could be demonstrated.

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Alteration of pancreatic B-cells in Wistar rats treated with non-diabetogenic doses of cyclosporin A.

We have investigated the effect of non-immunosuppressive cyclosporin A (CS-A) doses on glucose tolerance, pancreatic insulin content, insulin content of isolated islets and insulin secretion in vitro in response to glucose. Within 12 weeks animals treated permanently with a dose of 2.5 mg CS-A/kg b.wt. developed glucose intolerance (but not hyperglycaemia) accompanied by a decrease of pancreatic insulin content due to a decrease of islet insulin content, whereas the relative B-cell volume density was not changed. Isolated islets obtained from rats treated for 4 weeks had a diminished sensitivity for glucose, whereas islets obtained from animals treated for greater than 4 weeks showed a diminished half-maximum and maximum secretion rate. Rats treated for 12 weeks with 1.25 mg CS-A/kg b.wt. developed an impaired glucose tolerance after 8 weeks accompanied by a diminished pancreatic insulin content. Despite continued treatment the pancreatic insulin content was able to increase and the glucose tolerance to normalize, indicating an adaptation of pancreatic B-cells to CS-A. The results support the theory that a potential toxic effect of cyclosporin A can be diagnosed by functional tests (e.g. insulin secretion in response to a stepwise increase of glucose) before the irreversible (e.g. morphological) alterations occur.

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Prevention and suppression of autoimmune pancreatic beta-cell destruction in BB rats by syngeneic lymphocytes obtained from long-term normoglycaemic donors.

To prove whether a cell-mediated mechanism is responsible for maintaining long-term normoglycaemia in BB/OK rats with a proved immune attack (insulitis, reduced Beta-cell volume), we transferred lymphocytes obtained from those rats into normoglycaemic diabetes-prone BB/OK rats or into diabetic BB/OK rats receiving a simultaneous syngeneic islet graft. Our results show the presence of a lymphocyte population in the long-term normoglycaemic BB/OK rats, which is able to arrest pancreatic Beta-cell destruction in diabetes-prone BB/OK rats detected by a decreased diabetes incidence following single lymphocyte transfusion. Syngeneic islets were destroyed by recurrence of the autoimmune process when transplanted into diabetic BB/OK rats. Lymphocytes obtained from long-term normoglycaemic BB/OK rats were able to protect the syngeneic BB/OK islet graft from autoimmune destruction in diabetic BB/OK rats, whereas allogeneic islet destruction was not prevented. The phenotype of the effective lymphocyte population is not yet clear, but it is negative for RT6. We conclude that the mechanism responsible for maintaining normoglycaemia in long-term normoglycaemic BB/OK rats is cell mediated, because this property can be transferred to prevent autoimmune destruction of pancreatic Beta cells.

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