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Biomedical subjects

L Jansson

Publications and source records attributed to L Jansson.

At least 127 records · Page 7Linked to original sources
PubMed1995

Effects of the biguanide metformin on splanchnic blood flow in rats: preferential and dose-dependent increase in islet blood flow.

The aim of the present study was to evaluate if metformin, a biguanide used in the treatment of noninsulin-dependent diabetes, induced any changes in splanchnic circulation. For this purpose, anesthetized rats were injected intraperitoneally with saline alone (1 ml/kg BW) or metformin (15 or 30 mg/kg BW) 30 min before blood flow measurements. No effects on blood glucose or serum insulin concentrations could be discerned after administration of metformin. Both duodenal, whole pancreatic and islet blood flow were approximately doubled by the lowest dose (15 mg/kg BW) metformin. However, the higher dose (30 mg/kg BW) did not affect duodenal or pancreatic blood flow, whereas islet blood flow was markedly increased also in this group of animals. It is concluded that the blood flow to the pancreatic islets can be specifically enhanced by metformin. To what extent this contributes to the antihyperglycemic action of the drug is presently unknown.

Animals↗
PubMed1995

Influence of corticotropin-releasing factor on pancreatic and islet blood flow in different regions of the rat pancreas.

Corticotropin-releasing factor (CRF) has previously been shown to selectively dilate the mesenteric vascular bed, without affecting other vascular beds. Pancreatic blood flow and islet blood flow were therefore measured separately with a microsphere technique in the two regions of the rat pancreas perfused by the superior mesenteric artery (SMA) or celiac artery (CA) respectively. Intravenous infusion of CRF (0.25 microgram/kg b.w./min) caused an increase in both whole pancreatic blood flow and islet blood flow in the region of the pancreas perfused by the SMA. The fraction of whole pancreatic blood flow diverted through the islets in this part of the pancreas was, however, unaffected by CRF infusion (approximately 10%). CRF did not change either pancreatic or islet blood flow in the CA-perfused part of the pancreas, and did not affect the release of insulin.

Animals↗
PubMed1995

Impairment of glucose-induced insulin secretion in human pancreatic islets transplanted to diabetic nude mice.

Hyperglycemia-induced beta-cell dysfunction may be an important component in the pathogenesis of non-insulin-dependent diabetes mellitus. However, most available data in this field were obtained from rodent islets. To investigate the relevance of this hypothesis for human beta-cells in vivo, human pancreatic islets were transplanted under the renal capsule of nude mice. Experimental groups were chosen so that grafted islets were exposed to either hyper- or normoglycemia or combinations of these for 4 or 6 wk. Grafts of normoglycemic recipients responded with an increased insulin release to a glucose stimulus during perfusion, whereas grafts of hyperglycemic recipients failed to respond to glucose. The insulin content of the grafts in the latter groups was only 10% of those observed in controls. Recipients initially hyperglycemic (4 wk), followed by 2 wk of normoglycemia regained a normal graft insulin content, but a decreased insulin response to glucose remained. No ultrastructural signs of beta-cell damage were observed, with the exception of increased glycogen deposits in animals hyperglycemic at the time of killing. It is concluded that prolonged exposure to a diabetic environment induces a long-term secretory defect in human beta-cells, which is not dependent on the size of the islet insulin stores.

Adolescent↗
PubMed1995

Diabetes in pregnancy: uterine blood flow and embryonic development in the rat.

The uterine blood flow to individual implantation sites was evaluated in early normal and diabetic rat pregnancy, and related to maternal metabolic state, length of gestation, and embryonic outcome. The aim was to search for a possible coupling between the flow rate and embryonic development. We studied pregnant rats of a malformation-prone Sprague-Dawley strain on gestational d 9, 10, 11, and 12, a time period which roughly corresponds to postconception wk 3-6 in human gestation. The blood flow in the uterus was estimated with the aid of a microsphere technique, and the embryos were evaluated with respect to morphology and uterine position. We found increased blood flow in the uterine and decidual tissue of the pregnant diabetic animals compared with normal pregnant rats on all days studied. The blood perfusion peaked on gestational d 10, both in normal and diabetic pregnancy. The implantations tended to be fewer, whereas the resorption and malformation rates were higher, in the left horn than in the right horn. The blood flow in the uterine and decidual tissues was increased in the left horn in diabetic d 10 tissue, as well as d 12 tissues, thereby suggesting that compromised embryonic development is associated with increased rather than decreased supply of nutrients to the implantation site. These findings are in concert with previous in vitro results suggesting that enhanced oxidative stress due to increased substrate availability is an important factor in diabetic teratogenesis.

Animals↗
PubMed1995

A defective stimulus-secretion coupling rather than glucotoxicity mediates the impaired insulin secretion in the mildly diabetic F1 hybrids of GK-Wistar rats.

Adult F1 hybrids of male GK and female Wistar control rats exhibit mild, spontaneous non-insulin-dependent diabetes mellitus characterized by impaired glucose-induced insulin secretion. Using isolated pancreatic islets of hybrid rats, we first studied whether impaired glucose-induced insulin response is present not only in adult but also in neonatal rats. Furthermore, we investigated whether the impaired glucose-induced insulin response can be restored by long-term normalization of glycemia. Both 1-week- and 2- to 3-month-old hybrid rats had similar body weights but increased fed blood glucose levels (P < 0.05) compared with age-matched control rats. At 5.5 mmol/l glucose, insulin release was two- to threefold lower in isolated islets of hybrid than in control rats of both age groups (P < 0.05). At 16.7 mmol/l glucose, insulin secretion from hybrid islets was approximately 25% of that from control islets of both 1-week- and 2- to 3-month-old rats. For the second objective, batches of 250 islets from hybrid or control rats were transplanted under the kidney capsule of athymic, normoglycemic nude mice and maintained there for 4 weeks. Perfusion of kidneys demonstrated that glucose-induced (16.7 mmol/l) insulin secretion was impaired markedly in hybrid grafts compared with that in control grafts (0.66 +/- 0.23 vs. 1.8 +/- 0.38 pmol/20 min; P < 0.01), whereas stimulation by 20 mmol/l arginine resulted in similar insulin responses in both groups. The volumes of the grafted islets were similar in kidneys bearing either control or hybrid islets.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Ultrastructural evidence for blood microvessels devoid of an endothelial cell lining in transplanted pancreatic islets.

The aim of the present study was to investigate, at the ultrastructural level, the process of revascularization of freshly isolated islets or cultured islets after transplantation under the kidney capsule of syngeneic mice. Native islets in adult pancreases from mice, pigs, and humans contained only capillaries with fenestrated endothelium. However, the endothelial cell lining was disrupted in both freshly isolated and cultured mouse islets. Shortly after transplantation (6 weeks) approximately 80% of graft microvessels contained no endothelial cell lining. Similar data on microvessel morphology were found when fetal porcine islet-like cell clusters were implanted into athymic nude mice. Re-endothelialization was a slow process, with 25% of the microvessels still lacking endothelium 6 months after transplantation of cultured mouse islets or islet-like cell cluster. However, when freshly isolated mouse islets are used only 25% of microvessels within the islet graft lacked endothelium 6 weeks after implantation. We suggest that capillaries damaged during islet isolation may provide a preformed channel, serving as a scaffold for newly formed islet graft blood vessels. The presence of non-endothelialized microvessels, with an associated lack of barrier function, might make transplanted islets more prone to thrombosis or an attack by the immune system. This provides a tentative explanation for the increased vulnerability of islet grafts when compared with whole pancreas transplants.

Animals↗
PubMed1994

Mental illness in the biological and adoptive relatives of schizophrenic adoptees. Replication of the Copenhagen Study in the rest of Denmark.

BACKGROUND: Our previous investigation of the prevalence of mental illness among the biological and adoptive relatives of schizophrenic adoptees in Copenhagen, Denmark, showed a significant concentration of chronic schizophrenia (5.6%) and what Bleuler called "latent schizophrenia" (14.8%) in the biological relatives of chronic schizophrenic adoptees, indicating the operation of heritable factors in the liability for schizophrenic illness. METHODS: We now report the results of a replication of that study in the rest of Denmark (the "Provincial Sample"). RESULTS: In this sample, the corresponding prevalences were 4.7% and 8.2%. In the combined "National Sample" of adoptees with chronic schizophrenia, that disorder was found exclusively in their biological relatives and its prevalence overall was 10 times greater than that in the biological relatives of controls. CONCLUSIONS: This study and its confirmation of previous results in the Copenhagen Study speak for a syndrome that can be reliably recognized in which genetic factors play a significant etiologic role. These findings provide important and necessary support for the assumption often made in family studies: observed familial clustering in schizophrenia is an expression of shared genetic factors.

Adolescent↗
PubMed1994

The Y chromosome-linked "autoimmune accelerating" yaa gene suppresses collagen-induced arthritis.

The Y-linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease. We have investigated the role of the yaa gene in the development of the type II collagen (CII)-induced arthritis (CIA), which is used as a model for rheumatoid arthritis. In contrast to the accelerating effects on development of lupus autoimmunity we can show that the presence of BXSB Y chromosome carrying the yaa gene block development of CIA in F1 crosses with three normally CIA-susceptible strains, DBA/1, C3H.Q and B10.Q. Backcross experiments showed an additional modulatory effect from other BXSB genes or possibly from DBA/1 X chromosome. To evaluate the effect mediated by the yaa gene alone, the BXSB Y chromosome was bred into the DBA/1 gene background. The DBA/1 congenic DBA/1.yaa male mice were less susceptible to arthritis development than their DBA/1 counterparts. (B10.QxDBA/1.yaa)F1 acquired resistance to arthritis development similar to that of DBA/1.yaa, indicating a role for the yaa gene alone. The serum levels of autoantibodies to CII were significantly suppressed in all strains carrying yaa. In DBA/1.yaa mice a reduced number of T cells were found to produce interferon-gamma after in vitro stimulation with CII. Thus, although autoreactive B cells are important in both diseases they play different roles in murine lupus and in CIA.

Animals↗
PubMed1994

Expression of a transgenic class II Ab gene confers susceptibility to collagen-induced arthritis.

The major histocompatibility complex (MHC) class II region is assumed to influence autoimmune diseases such as rheumatoid arthritis. In the mouse, the H-2q haplotype is associated with susceptibility to collagen-induced arthritis, while the H-2p haplotype is not. The class II A molecules of these haplotypes differ by only four amino acids in the first domain of the beta chain. To test if this difference accounts for the MHC influence on susceptibility to collagen-induced arthritis, H-2p mice were made transgenic with an Abp gene altered to resemble the Abq gene. The transgenic A beta chain hybridized with the A alpha p chain and was shown to be physiologically expressed by testing antigen-presentation capacity to Aq-restricted T cell hybridomas and with FACS analyses. These transgenic mice developed an autoimmune response to type II collagen and also collagen-induced arthritis. The data unequivocally suggest the Ab gene as a major genetic susceptibility locus for autoimmune collagen-induced arthritis.

Animals↗
PubMed1994

Chronicity of arthritis induced with homologous type II collagen (CII) in rats is associated with anti-CII B-cell activation.

DA rats develop chronic arthritis after immunization with native rat type II collagen (CII) emulsified in incomplete Freund's adjuvant (IFA) (= collagen-induced arthritis, CIA). The same rat strain develops an acute, self-limited form of arthritis after injection with IFA alone (= oil-adjuvant-induced arthritis, OIA). The induction of a chronic course of arthritis, as well as an anti-CII antibody response, was dependent on the dose of CII; 30 micrograms induced a self-limited disease course and no B-cell response, while 150 micrograms induced a chronic disease course and a strong B-cell response. Immunization with denatured rat CII induced only acute arthritis, similar to OIA. To investigate why IFA or denatured CII/IFA induced only acute disease while native CII/IFA induced chronic disease, we analysed the immune responses to CII. Both native and denatured CII induced a weak but significant autoreactive T-cell response while only native CII induced a strong B-cell response to CII. IFA did not produce a significant immune response to CII. Interestingly, rats that had developed acute arthritis after immunization with denatured CII/IFA were vaccinated against CIA, but not rats that had developed arthritis induced with IFA only. Rats vaccinated against CIA after pretreatment with denatured CII/IFA had an anti-CII antibody response that was almost eliminated. In addition, pretreatment of rats with denatured or native rat CII in olive oil, which does not induce arthritis, vaccinated against a subsequent induction of arthritis with native rat CII. Again, the vaccination suppressed the anti-CII B-cell response. We suggest that activated B-cells, reactive with conformational epitopes on CII, are of importance for the chronic development of CIA.

Animals↗
PubMed1994

Acute effects of different immunosuppressive drugs on pancreatic, islet, renal, and arterial hepatic blood flow in anesthetized rats.

The effects of four different immunosuppressive drugs on organ blood flow were investigated. Sprague-Dawley rats were injected intravenously with 0.2 ml of either 15-deoxyspergualin (DSG; 5 mg/kg body weight), RS 61443 (80 mg/kg body weight), FK 506 (0.5 mg/kg body weight), cyclosporin A (9.5 mg/kg body weight), or the vehicles used. At 15 or 60 min after injection of the drugs, the blood perfusion of the whole pancreas, the pancreatic islets, and the kidneys, as well as the arterial blood flow to the liver, were measured in anesthetized animals using a microsphere technique. Fifteen minutes after administration, both FK 506 and DSG decreased the fraction of whole pancreatic blood flow diverted through the islets. FK 506 and cyclosporin A reduced renal blood flow, but only 60 min after injection of the drug. None of the drugs influenced hepatic blood flow. RS 61443 did not affect the blood flow of the organ systems investigated. These differences in the effects of the drugs tested on blood flow might have some important implications on their efficacy and side effects. Thus, in view of its lack of influence on organ blood flow, RS 61443 seems to be preferable, at least when compared with cyclosporin A and FK 506 in the context of organ transplantation.

Anesthesia↗
PubMed1994

Vasoactive intestinal polypeptide increases whole pancreatic blood flow but does not affect islet blood flow in the rat.

To evaluate the effects of vasoactive intestinal peptide (VIP) on whole pancreatic blood flow and islet blood flow in the rat, anaesthetized adult rats were injected intravenously for 90 s with VIP (500 ng/kg body weight). Immediately after the injection, the whole pancreatic and islet blood flows were measured with a microsphere technique. VIP markedly increased the former but did not affect the latter. Thus, the fraction of the whole pancreatic blood flow diverted through the islets was decreased. In separate experiments, the effects of VIP on the blood glucose and serum insulin concentrations of anaesthetized animals were investigated. VIP caused an acute increase (after 2 min) in the latter, but did not affect the former. It is concluded that VIP exerts its blood flow stimulatory properties only on the exocrine pancreas, and that it may increase the serum insulin concentrations without an associated change in islet blood perfusion.

Animals↗
PubMed1994

Estrogen induces a potent suppression of experimental autoimmune encephalomyelitis and collagen-induced arthritis in mice.

We have earlier described a chronic relapsing experimental autoimmune encephalomyelitis (EAE) in B10.RIII mice induced with a peptide of myelin basic protein (MBP), mimicking the course of multiple sclerosis in man. We now show that estrogens ameliorate chronic EAE. Castration of female mice led to an earlier disease onset (day 9 +/- 2 postimmunization (p.i.) in castrated mice vs. day 16 +/- 4 p.i. in normal mice). Long-term treatment with high levels of 17 beta-estradiol (E2) given as Silastic implants led to a dramatically delayed onset of disease in both castrated and normal female mice (mean onset day was day 39 +/- 14 and day 50 +/- 3, respectively). Treatment of castrated females by injections of E2, at a concentration which induces the serum levels seen at late stage pregnancy, delayed the onset approximately 1 week (mean onset 21 +/- 8). In contrast, treatment with estriol (E3), which was also given at doses corresponding to those levels seen during pregnancy, delayed the disease onset for a longer time (mean onset day 31 +/- 5). Five times higher doses of E2, compared with those seen during pregnancy, were required to obtain similar effects as the low E3 dose. The same mouse strain (B10.RIII) is also susceptible to induction of collagen-induced arthritis (CIA). We show here that also CIA is suppressed by the same treatments with E2 and E3, suggesting that similar estrogen-mediated mechanisms may operate to suppress these T-cell-dependent autoimmune disease models.

Animals↗
PubMed1994

The long-acting somatostatin analogue octreotide decreases pancreatic islet blood flow in rats.

The effects of intravenously administered octreotide (5 or 10 micrograms/kg body weight) on pyloric, duodenal, colonic, pancreatic, and islet blood flow were investigated with a microsphere technique in anesthetized rats. The lower dose of octreotide reduced only pyloric blood flow, while the higher dose caused a reduction also in duodenal and colonic blood flow. Whole pancreatic blood flow was not affected by either of the doses of octreotide, but the blood flow through the islets was decreased by the higher dose. Also, the fraction of whole pancreatic blood flow through the islets was decreased by the higher dose. It is concluded that octreotide mainly affects intestinal blood flow, but not whole pancreatic blood flow in rats. However, octreotide causes a redistribution of the blood flow within the pancreas, which leads to a diminished islet blood perfusion, in conjunction with a decrease in serum insulin concentration.

Animals↗
PubMed1994

Proximal restorations and periodontal status.

The purpose of the present investigation was to evaluate the influence of overhanging marginal restorations on periodontal status and whether any such influence is modified by the patient's oral hygiene level and degree of radiographic attachment loss. The investigation was conducted as a retrospective study on a consecutive referral population. Periodontal pockets at proximal sites with marginal overhangs were significantly deeper (0.42 mm) compared to sites with metal restorations without overhangs. This difference was larger (0.62 mm) for sites with radiographic attachment loss < or = 6 mm, while no significant difference was found for sites with radiographic attachment loss > 6 mm. In patients with a mean radiographic attachment loss < or = 5 mm, an overhanging restoration margin was associated with a significantly increased loss of radiographic attachment (0.66 mm). It was concluded that the influence of a marginal overhang on pocket depth and radiographic attachment decreases with increasing loss of periodontal attachment in periodontitis-prone patients. The effect on pocket depth of a marginal overhang may act synergistically, potentiating the effect of poor oral hygiene.

Adult↗
PubMed1994

Characterization of mixed syngeneic-allogeneic and syngeneic-xenogeneic islet-graft rejections in mice. Evidence of functional impairment of the remaining syngeneic islets in xenograft rejections.

Allogeneic mouse islets or xenogeneic rat islets, or fetal porcine islets were implanted under the renal capsule of C57BL/6 mice either alone or carefully mixed with syngeneic islets. With this experimental model the syngeneic islets, although not rejected themselves, are exposed to cytokines and inflammatory mediators released during either allograft or xenograft rejection. No differences in insulin content could be observed between mixed islet grafts and pure syngeneic islet grafts 6 wk after transplantation. Neither was there any morphological evidence of a non-specific destruction of syngeneic islets. These findings suggest that the mechanisms of both allograft and xenograft rejections are highly specific. The hormone release from the mixed syngeneic-allogeneic grafts was similar to that from pure syngeneic islet grafts. In contrast, a pronounced impairment of both the first and second phases of insulin release was observed 2 wk after implantation in mixed syngeneic-xenogeneic islet grafts. When perfusing the mixed islet graft after completed rejection of the concordant xenogeneic rat islets (6 wk after implantation), the insulin release from the remaining syngeneic mouse islets was identical to that of control grafts. However, syngeneic mouse islets exposed to the rejection mechanism of the discordant xenogenic pig islet-like cell clusters did not attain a complete functional recovery.

Animals↗