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Biomedical subjects

K Federlin

Publications and source records attributed to K Federlin.

At least 163 records · Page 9Linked to original sources
PubMed1991

Diabetes mellitus-associated decrease in nerve growth factor levels is reversed by allogeneic pancreatic islet transplantation.

After an untreated 5-month duration of streptozotocin (STZ)-induced diabetes mellitus (DM), nerve growth factor (NGF) levels in BDE rats were decreased to 45-65% of control in the sympathetically innervated target organs iris and submandibular gland, in the superior cervical ganglion (containing NGF-dependent sympathetic perikarya projecting to the cranial targets), and in the NGF-transporting sciatic nerve. Successful allogeneic pancreatic islet transplantation (providing a physiological glucose homeostasis without immunosuppression) after 3-4 weeks of DM reversed the DM-related decrease in NGF levels 4 months after transplantation as compared with untreated diabetic rats. By contrast, NGF levels in the treated vas deferens (innervated by short postganglionic sympathetic neurons) remained increased as in the untreated diabetic rats (175% of control). Thus, DM-associated changes in endogenous NGF levels seem to be reversible by institution of metabolic control, at least at an early stage of DM when NGF-responsive neurons have not been deprived of NGF for a long time.

Animals↗
PubMed1991

The effect of pancreatic islet transplantation on experimental diabetic neuropathy.

Quantitative light and electronmicroscopical morphometric techniques were used to determine the effect of pancreatic islet transplantation on experimental diabetic neuropathy. Groups of STZ-diabetic rats were given islet transplants at 3 weeks after diabetes onset (prevention) and at 6 months after diabetes onset (reversal). Comparisons were made with onset controls, age-matched non-diabetic controls and untreated diabetic controls 6 months later (n = 8 for all groups). Euglycaemia and normal levels of glycosylated haemoglobin were achieved in both groups of diabetics after islet transplantation. Loss of body weight in diabetic animals was prevented by early islet transplantation, but was only partially reversed following delayed islet transplantation. Normal growth of myelinated fibres and axons during development was retarded in untreated diabetics, but was normal in rats given islet transplants soon after the onset of diabetes (cross-sectional perimeter and area). Diabetics transplanted with islets after a delay had myelinated fibres and axons with diminished calibre. Teased fibre preparations of nerves from diabetics which had received islet transplants showed no excess of abnormalities. This study has shown that the development of certain structural abnormalities of peripheral nerve fibres is prevented in diabetic rats which receive transplants of islets of Langerhans soon after the onset of diabetes. However, once established abnormal fibre morphology can not be completely ameliorated merely by achieving and sustaining euglycaemia through delayed islet transplantation.

Animals↗
PubMed1991

Islet transplantation in experimental diabetes of the rat. XIII. Cryopreservation reduces MHC class II but not class I antigens of rat pancreatic islets.

Pretreatment of islet allografts prior to transplantation may reduce islet immunogenicity and prolong graft acceptance. We have studied the MHC antigen reducing effect of cryopreservation onto rat pancreatic islets performing indirect immunofluorescence tests and peroxidase-anti-peroxidase staining (PAP). Three different freezing programs were used. Program A: 0.5 degrees C/min to -35 degrees C and 1 degree C/min from -35 to -100 degrees C. Program B: 2 degrees C/min to -35 degrees C and 6 degrees C/min from -35 to -100 degrees C. Program C: 0.25 degrees C/min to -40 degrees C. Cryopreservation clearly reduced the number of class II antigen positive cells per islet in all cases. Program A was most effective with 45.5% of class II antigen negative islets compared to 6.4% of class II antigen negative fresh islets as shown by indirect immunofluorescence. The class II antigen reducing effect of cryopreservation proved to be permanent and not only temporary. Reduced class II antigen expression of cryopreserved islets could not be reestablished by incubation of the islets with rat IFN. A combination of cryopreservation followed by a 10 day culture period proved to be most effective with 85.6% of class II antigen negative islets. In contrast, we could not show any effect of cryopreservation on class I antigen expression. Viability of the cryopreserved rat islets was shown in-vitro by glucose stimulated insulin secretion.

Animals↗
PubMed1991

Pretreatment of rat pancreatic islets with MHC I-A monoclonal antibody: in-vitro and in-vivo effects on islet antigenicity.

Pancreatic islet allografts are rejected very rapidly due to their high immunogenicity. Several attempts have been made to reduce the immunogenicity prior to transplantation. We treated islets with MHC Ia (class II) antigen monoclonal antibody and complement in order to lyse Ia antigen bearing cells within the islets. This treatment caused a distinct reduction of Ia antigen positive cells, which was demonstrated by indirect immunofluorescence tests. A total depletion of the Ia antigens, however, could not be achieved. As a second in-vitro test to evaluate the effect of the antibody treatment a mixed lymphocyte islet culture (MLIC) was performed. The partial Ia antigen reduction provoked a significantly reduced but not completely suppressed allogenic T-cell response. Antibody treatment did neither impair the morphological integrity nor the function of the islets as could be demonstrated by syngenic transplantation of islets pretreated by antibodies in the same way. After allotransplantation of antibody-pretreated islets across a major histocompatibility barrier into non immunosuppressed rats, however, there was no significant prolongation of the graft survival. Thus, a partial reduction of the number of the Ia antigen positive cells within the islets is not sufficient for the prevention of allograft rejection.

Animals↗
PubMed1991

Further morphological and biochemical observations on early low dose streptozocin diabetes in mice.

Conflicting published data regarding the role of macrophages and other cell types during the early stages of diabetes mellitus led us to further study this problem. To this end we diabetized mice, using low doses of streptozocin (STZ), 40 mg/kg body wt/day/5 days, and processed their pancreatic tissue for immunocytochemistry and ultrastructural observations; immunohistochemistry was performed on days 5 and 18 after the first STZ injection, and islets were observed ultrastructurally on days 5, 9, 10, and 18. Animals were tested for fasting serum glucose, and isolated islets were assayed for insulin secretion capacity. Immunohistology demonstrated that expression of major histocompatability complex class 2 antigens is strongly induced by multiple, low dose STZ treatments prior to impaired insulin release, and that different types of cells within the islet are capable of expressing Ia molecules. Ultrastructurally we found (a) a small number of macrophages (most probably resident monocytes/macrophages) containing B-cell debris, that were located close to either damaged or intact B cells; (b) a large number of recruited macrophages in a vascular or perivascular position; and (c) macrophages recognizable in the exocrine portion, close to the islets, occasionally containing exocrine cell debris. This led us to believe that recruited macrophages play an important role in the early islet-infiltrating stage.

Animals↗
PubMed1991

Detection of circulating Fc epsilon R2/CD23+ monocytes in patients with rheumatic diseases.

Recently, in vitro studies have demonstrated that expression of Fc epsilon R2/CD23 on normal monocytes can be specifically induced by IL-4. In order to investigate the interaction of IL-4 and monocytes in rheumatic diseases, flow cytometry studies were performed. Elevated numbers of circulating Fc epsilon R2/CD23+ monocytes were detected in patients with progressive systemic sclerosis (PSS) as compared with controls. In addition, supernatants derived from phytohaemagglutinin-stimulated peripheral blood mononuclear cells of PSS patients contained high activity to induce Fc epsilon R2/CD23 on CD14+ monocytes. An increased frequency of Fc epsilon R2/CD23+ monocytes was also observed in rheumatoid arthritis, and sequential studies in patients with systemic lupus erythematosus showed a close relationship between Fc epsilon R2/CD23+ monocytes and disease activity. It is suggested that IL-4 has an important role in the pathogenesis of PSS by activating monocytes, and might also contribute to monocyte activation in other rheumatic diseases.

Adult↗
PubMed1991

Light- and electron-microscopic studies on isolated bovine islets of Langerhans.

While several recent studies have focussed on the critical assessment of yield, purity and function of isolated islets, fine-structural investigations of isolated islets have been the subject of only a few studies. After intraductal injection of collagenase solution, the distended bovine pancreata were processed in a continuous digestion-filtration device, after which the purification of the islet suspension was accomplished by density gradient centrifugation. Purified islets were then prepared for light- and transmission electron-microscopic analysis. In semithin sections, no evidence of either connective tissue or exocrine tissue surrounding isolated islets was found. Endocrine cells exhibiting cytoplasmic granules were packed in clusters varying in size. In ultrathin sections, A-cells containing numerous secretory granules were distinctive; their cytoplasm contained conspicuous formations of rough endoplasmatic reticulum and juxtanuclear Golgi complexes. In the B-cells, the Golgi complexes were also prominent; these elements, however, were poor in endoplasmic reticulum and displayed characteristic B-cell granules surrounded by a halo. A few ultrastructurally heterogeneous cells were scattered among the identified cellular elements.

Animals↗
PubMed1991

[Does insulitis have importance in the pathogenesis of type-1 diabetes in man?].

Insulitis is a lymphocytic infiltration of islets of Langerhans occurring together with a selective loss of beta cells. Infiltrating cells spread from peripheral islet vessels to the centre of a given islet. In humans, insulitis is believed to be associated with autoimmune phenomena, e.g. autoantibodies to beta cells. Insulitis is seen in IDDM of man with young age of onset and short duration of disease. In animal models, insulitis is not necessarily associated with autoimmunity. From animal studies it is known that insulitis does not always end up with manifestation of diabetes in a given animal. Experimental data provide evidence for a dysregulated immune system recognizing beta-cell-specific antigens and producing beta-cell-cytotoxic lymphocytes. On the other hand, the surface of the beta cell changes induced by viral infection or environmental toxins and thereby becomes the target of an immune attack.

Animals↗
PubMed1991

[Autoantigens in type-I diabetes].

The juvenile form of diabetes, type-I diabetes mellitus, is, to our knowledge of today, an autoimmune disease with the hallmark of selective destruction of the insulin-producing beta cells in the endocrine pancreas. The slow, progressive process is in strong contrast with the sudden onset of clinical disease. The identification of target antigens has implications for both, better diagnostic at an earlier time as well as for new forms of therapy such as induction of tolerance or T-cell vaccination. Next to the direct products of the beta cell, insulin and proinsulin, two antigens of 38 resp. 64 kD molecular weight, have been identified. Other possible antigens include carboxypeptidase H and a heat-shock protein of 65 kD. The identity of the antigen recognized by islet-cell antibodies, the most frequently used marker for type-I diabetes mellitus, remains a subject of discussion.

Autoantibodies↗
PubMed1991

[Islet transplantation in the treatment of diabetes mellitus: the challenges to the transplant of rejection and recurrent autoimmunity].

The success of islet transplantation for therapy of spontaneous diabetes mellitus depends on two immune responses of the recipient. The rejection of foreign tissue plays a major role in islet transplantation and can successfully be prevented by different immunomodulation in animals. In spontaneous diabetes the islet transplant can also be destroyed by the recurrent autoimmune insulitis. We describe, in which experiments recurrence occurred. We also demonstrate the influence of the donor-host combination on the immune attack and the possibilities to prevent the destruction of transplanted islets in animals. An outlook on the clinical situation is given.

Autoimmunity↗
PubMed1991

[T-helper cell subsets in patients with inflammatory rheumatic diseases undergoing immunosuppressive therapy].

To determine the influence of immunosuppressive therapy on T-helper-cell subsets in patients with systemic lupus erythematosus and rheumatoid arthritis flow cytometric analysis was performed. Longitudinal studies showed reduced numbers of CD45R+CD4+ lymphocytes in patients treated with cyclophosphamide or azathioprine. Patients receiving steroids had low frequencies of CD29+CD4+ cells. The data suggest that cytotoxic drugs and steroids affect T-helper cells at different activation stages.

Antineoplastic Agents↗
PubMed1991

Serum osteocalcin levels in rheumatoid arthritis: a marker for accelerated bone turnover in late onset rheumatoid arthritis.

Levels of serum osteocalcin (OC) are increased in diseases with high bone turnover. We determined OC levels in (1) 15 patients with definite rheumatoid arthritis (RA) in early stages according to Steinbrocker's functional class FC I-II, (2) 40 patients at advanced stages (FC III-IV) and (3) 17 patients with late RA (onset at age of 65 or more). Sixty-two healthy volunteers, divided into 3 subgroups corresponding to the patients, and 19 patients with primary fibromyalgia syndrome (FMS) served as controls. All patients were included in a short term as well as a longitudinal study over one year. Mean OC levels were significantly elevated in patients with late onset RA compared with healthy controls (p = 0.037), while the OC values in early RA FC I-II and advanced RA FC III-IV did not differ significantly from the corresponding control group and the patients with FMS. The late RA group showed a positive correlation between OC and the erythrocyte sedimentation rate (ESR) (r = 0.641, p = 0.007) with a significant decrease of OC (p less than 0.01) as well as ESR (p = 0.047) over one year. We conclude increased OC levels correlate with disease activity in older patients with active RA, suggesting impaired bone turnover. This finding supports the picture of heterogeneity in RA with more late onset patients displaying "high bone turnover."

Adult↗