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Biomedical subjects

L Jansson

Publications and source records attributed to L Jansson.

At least 181 records · Page 10Linked to original sources
PubMed1991

Partial pancreatectomy in rats causes an impairment of the glucose-induced stimulation of pancreatic islet blood flow.

Adult rats were subjected to either a sham operation (S-rats) or a 60% partial pancreatectomy (P-rats). Both P- and S-rats were normoglycemic and normoinsulinemic after surgery. Four weeks later, the animals were injected i.v. with 1 ml of either 0.9% (w/v) saline or 30% (w/v) D-glucose, and after 5 min whole pancreatic blood flow (PBF) and islet blood flow (IBF) were measured, using a microsphere technique. In the saline-injected P-rats both PBF and IBF values were higher than in S-rats (p less than 0.001 for both values). Administration of glucose had no effects on PBF in either S- or P-rats when compared to saline-injected animals. IBF was, however, markedly increased (p less than 0.01) by glucose in S-rats in comparison with saline-injected S-rats, whilst no difference in IBF was observed between glucose- and saline-injected P-rats. The fraction of PBF diverted through the islets (fIBF) was approximately 10% in S-rats and 20% in P-rats. Glucose increased fIBF in S-rats, but had no effect in P-rats. In conclusion, in S-rats a glucose-stimulated insulin release is accompanied by an increase in IBF, but this is not observed in P-rats.

Animals↗
PubMed1991

Chronic experimental autoimmune encephalomyelitis induced by the 89-101 myelin basic protein peptide in B10RIII (H-2r) mice.

Development of experimental allergic encephalomyelitis (EAE) in the SJL (H-2s) mice is associated with a T cell-dependent autoimmune response to the C-terminal part of the myelin basic protein (MBP). In this study the influence of both H-2 and non-H-2 genetic background on EAE induced with the MBP89-101 peptide is described. Analysis of different H-2q haplotype strains, B10G, B10Q, SWR and NFR/N, showed that the B10 background is relatively resistant to disease induction. Both SWR and NFR/N were susceptible to EAE showing that the H-2q haplotype is permissive for EAE development induced with MBP89-101 and that the T cell receptor (TcR) haplotype or complement C5 deficiency exert no significant influence on disease susceptibility. In a series of H-2-congenic strains on the B10 background only B10RIII (H-2r) mice were susceptible to EAE. The B10RIII mice developed a severe EAE with early onset and chronic progressive or relapsing course of disease. In addition, B10RIII mice treated with Freund's complete adjuvant and pertussis toxin alone showed an early monophasic disease. The clinical observations were confirmed by immunohistopathologic analysis of the central nervous system. In these studies, we also applied antibodies to different TcR V beta elements which showed no specific limitation of the used TcR among infiltrating T cells in the target tissue in any of the strains. It is concluded that an MBP peptide-specific disease can be induced in three different haplotypes and it is possible that shared structures between the As, Aq and Ar molecules are of importance for the trigger of encephalitogenic T cells with different TcR V elements. The presently described chronic EAE model induced in the B10RIII mice will be of value as a model for multiple sclerosis.

Adjuvants, Immunologic↗
PubMed1991

Functional and morphological differentiation of fetal porcine islet-like cell clusters after transplantation into nude mice.

By using a previously described culture technique for the midgestational fetal porcine pancreas, islet-like cell clusters with a Beta-cell frequency of approximately 5% have been produced in large numbers. These islet-like cell clusters were transplanted beneath the kidney capsule to either normoglycaemic or alloxan-treated nude mice. The grafts consistently failed to cure the alloxan-treated mice immediately after implantation, however, normoglycaemia was restored in a majority of the mice within 2 months after transplantation and in all animals after 4 and 6 months. Indeed, the insulin released from the transplanted fetal Beta cells was able to normalize the serum glucose concentration at porcine levels (4-5 mmol/l) rather than at the level maintained in mice (8-10 mmol/l). In the cured mice there was a normal secretory response to glucose in the grafts as evidenced by normal glucose profiles during intravenous glucose tolerance test and a biphasic insulin response to high glucose when perfusing the graft bearing kidney. On the other hand, in the normoglycaemic animals the second phase faded before the glucose stimulus had been withdrawn. Two months after transplantation the endocrine cells were arranged so that the endocrine non-Beta cells were randomly scattered among a majority of Beta cells. The cell replication of the Beta cells, measured by 3H-thymidine incorporation, was within the lower range of that seen in the native islets of adult mice. No major differences between the controls and the alloxan-treated animals were observed in this respect. Cultured islet-like cell clusters had high rates of glucose utilization, paralleled by low rates of glucose oxidation, compared with adult mouse islets.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan↗
PubMed1991

The nitric oxide synthase II inhibitor NG-nitro-L-arginine stimulates pancreatic islet insulin release in vitro, but not in the perfused pancreas.

The effects of L-arginine and its derivatives NG-methyl-L-arginine (Meth-arg) and NG-nitro-L-arginine (Nit-arg) on the insulin release and glucose oxidation of isolated rat islets were investigated to evaluate possible influences of nitric oxide. Also, the insulin release and flow distribution within the perfused rat pancreas were studied in response to these agents. Arginine, Meth-arg, and Nit-arg stimulated insulin release in cultured islets, but had no effect on glucose oxidation. Arginine and Meth-arg, an inhibitor of the enzyme nitric oxide synthase I (NS-I) stimulated insulin release from the perfused pancreas. Nit-arg, however, which inhibits nitric oxide synthase II (NS-II) had no such effect. Neither arginine nor Nit-arg or Met-arg changed the distribution of microspheres within the perfused pancreas. We conclude that interference with NS type I or II has no effect on insulin release from cultured islets, but inhibition of NS-II abolishes the insulin response in the perfused pancreas, which may be mediated by factors released from endothelial cells. These effects are not due to any changes in the flow distribution within the pancreas. The lack of inhibitory effect by Nit-arg in cultured islets may reflect the absence of endothelial or nervous cells in the cultured islets.

Amino Acid Oxidoreductases↗
PubMed1990

Estrogen induced suppression of collagen arthritis. V: Physiological level of estrogen in DBA/1 mice is therapeutic on established arthritis, suppresses anti-type II collagen T-cell dependent immunity and stimulates polyclonal B-cell activity.

Immunization of castrated female DBA/1 mice with rat type II collagen (CII) induces severe polyarthritis with an onset 3-5 weeks after immunization and with 80-100% incidence. Estrogen treatment, inducing physiological 17 beta-estradiol (E2) levels, during a limited period before and after the immunization, or during another period before the expected onset of arthritis, delayed the arthritic onset by approximately 10 days but did not affect the incidence of severity of arthritis. Treatment with physiological doses of E2 after onset of arthritis decreased severity and duration of disease. The T-cell dependent anti-CII autoantibody response was suppressed if the E2 treatment was given immediately before and after CII immunization and was not significantly affected if E2 treatment was given after CII immunization. Neither the total anti-CII Ig levels nor the anti-CII IgG2a levels correlated with development of arthritis. We also titrated the serum levels of estrogen and recorded the vaginal smear response after injections of various doses of E2. This enabled us to work in a physiological range of estrogen levels, spanning the levels found at the end of pregnancy and those found during the normal estrous cycle. These levels were found to suppress antigen-specific T-cell functions but enhance certain B-cell activities since the delayed type hypersensitivity (DTH) reaction against CII was suppressed while the total number of splenic Ig-secreting cells increased. These findings suggest that estrogen in physiological doses is therapeutic for the development of collagen-induced arthritis and that estrogen exerts dualistic effects on the immune system by suppressing T-cell functions and stimulating certain B-cell activities. The suppressive effect on arthritis could not be explained by suppression of anti-CII autoantibody response and must therefore depend on other T-cell-mediated functions.

Analysis of Variance↗
PubMed1990

Arthritis in DBA/1 mice induced with passively transferred type II collagen immune serum. Immunohistopathology and serum levels of anti-type II collagen auto-antibodies.

Arthritis was induced in DBA/1 mice by passive transfer of syngeneic anti-type II collagen (CII) serum concentrate. After transfer of serum containing 0.2 or 0.5 mg anti-CII auto-antibodies the first clinical signs of arthritis appeared 48 h after injection. Severe clinical arthritis was detected 96 h after injection. Immunohistochemical analyses of joints 48 h after serum injection revealed synovial foci in intercarpal and metacarpophalangeal joints of macrophage-like cells, expressing C3bi-receptors and major histocompatibility complex class II molecules, and infiltration of few CD4+ lymphocytes. Later (96 h after injection), the inflamed synovia were dominated by C3bi-receptor+ polymorphonuclear cells. In contrast to conventionally induced collagen arthritis (CIA), the inflammatory infiltrates, filling joint spaces and synovial tissue, were extensively dominated by polymorphonuclear cells, whereas macrophage-like cells expressing class II molecules and a few T cells were seen only in the periphery of the developing pannus. The anti-CII serum induced arthritis may be used as a model for studies of humoral mediated mechanisms operating in conventionally induced CIA as well as in rheumatoid arthritis.

Animals↗
PubMed1990

Altered blood flow regulation in autotransplanted pancreatic islets of rats.

Adult rats were partially depancreatized, and approximately 500 islets were isolated from each excised pancreas, maintained in tissue culture for 7 days, and subsequently transplanted back to the same animals beneath the renal capsule. Four weeks after transplantation the animals were anesthetized and given an intravenous injection of 1 ml of either saline, 30% (wt/vol) D-glucose, 30% (wt/vol) D-galactose, DL-propranolol (15 mg/kg body wt) dissolved in saline, or terbutaline (1 mg/kg body wt) dissolved in saline. Five minutes later blood perfusion of the islet grafts and the pancreatic remnant were measured with a microsphere technique. Islet blood flow was also measured in animals with pancreas intact and no islet grafts after administration of saline, glucose, or galactose. These animals demonstrated a significant and preferential increase in islet blood flow after glucose administration, whereas galactose caused a selective decrease in islet blood perfusion. Both whole pancreatic blood flow and islet blood flow in the pancreatic remnant were decreased by terbutaline administration, whereas the other substances had no effect. Blood flow to the transplanted islets was decreased by glucose and galactose, whereas propranolol and terbutaline had no effect compared with the saline-injected animals. These results suggest that blood flow regulation differs between transplanted pancreatic islets, islets in the normal pancreas, and islets in the pancreatic remnant after partial pancreatectomy. Whether this reflects lack of innervation or an altered reactivity of the newly formed blood vessels in islet grafts is presently unknown.

Animals↗
PubMed1990

Hyperglycemia-induced B cell toxicity. The fate of pancreatic islets transplanted into diabetic mice is dependent on their genetic background.

The role of pancreatic B cell dysfunction in the phase preceding clinical onset of insulin-dependent and non-insulin-dependent diabetes mellitus has been much debated. In this investigation, the impact of a prolonged diabetic environment on pancreatic islet B cells transplanted syngeneically under the kidney capsule of C57BL/6 (B6) and C57BL/Ks (BKs) mice was studied. Alloxan-diabetic mice bearing a subcapsular islet graft insufficient to normalize the blood glucose level were rendered normoglycemic by a second intrasplenic islet graft after various period of hyperglycemia to examine the reversibility of hyperglycemia-induced B cell dysfunction. Using a perfusion technique of the graft-bearing, it was found that both strains of mice exhibited a diminished glucose-induced insulin secretion after 6 wk of hyperglycemia, when compared with normoglycemic mice carrying islet grafts. When normoglycemia was restituted by the splenic graft after 4 or 12 wk, there was a normalization of glucose-stimulated insulin secretion in the renal islet grafts in B6 mice, whereas insulin secretion from the grafted BKs islets remained impaired. Morphometric measurements of the islet grafts demonstrated a 50% reduction in the graft volume in diabetic BKs mice after 12 wk, compared with normoglycemic animals, whereas no such decrease was observed in B6 mice. Islet grafts removed from hyperglycemic mice of both strains exhibited diminished insulin mRNA contents, and in the BKs mice there was also a reduced glucose oxidation rate in the islet grafts in vitro. This metabolic dysfunction can only partly be explained by a reduced graft size. The present findings emphasize the genetic constitution as a decisive factor for the survival and function during a period of sustained stress on a limited B cell mass.

Animals↗
PubMed1990

In vivo elimination of T cells expressing specific T-cell receptor V beta chains in mice susceptible to collagen-induced arthritis.

Type II collagen-induced arthritis (CIA) is believed to be dependent on T cells expressing a limited number of V beta chains. Two different methods were used to selectively eliminate T cells expressing a certain T-cell receptor (TcR) V beta chain in mouse strains susceptible to CIA. In vivo treatment with monoclonal anti-V beta 6 or anti-V beta 8.1,2 antibodies did not alter CIA, despite a reduction of the major part of the V beta 6+ or V beta 8.1,2+ lymph node cells (LNC), as measured by flow cytometric (FACS) analyses. The reduction was not due to complete elimination of V beta 6+ or V beta 8.1,2+ cells, since part of the V beta 6 and V beta 8.1,2 expressing cells returned later, even in mice that had been thymectomized first to prevent maturation of new T cells. In contrast, treatment with antibodies against CD4 efficiently abrogated development of CIA. In the (CBA x DBA/1J)F1 and the (BALB/c x DBA/1J)F1 mice, where M1s1a was combined with expression of I-E, the V beta 6+ LNC were deleted. In spite of the deletion, both F1 strains were highly susceptible to CIA.

Animals↗