Biomedical subjects

L Jansson

Publications and source records attributed to L Jansson.

At least 19 recordsLinked to original sources

PubMed2006

A perfusion protocol for highly efficient transduction of intact pancreatic islets of Langerhans.

AIMS/HYPOTHESIS: Successful gene transfer to pancreatic islets might be a powerful tool for dissecting the biological pathways involved in the functional impairment and destruction of beta cells in type 1 diabetes. In the long run, such an approach may also prove useful for promoting islet graft survival after transplantation in diabetic patients. However, efficient genetic modification of primary insulin-producing cells is limited by the specific compact structure of the pancreatic islet. We present here a whole-pancreas perfusion-based transduction procedure for genetic modification of intact pancreatic islets. MATERIALS AND METHODS: We used flow cytometry analysis and confocal microscopy to evaluate the efficiency of in vitro and perfusion-based transduction protocols that use adenoviral and lentiviral vectors expressing green fluorescent protein. Islet cell viability was assessed by fluorescence microscopy and beta cell function was determined via glucose-stimulated insulin secretion. RESULTS: In intact rat and human pancreatic islets, adenoviral and lentiviral vectors mediated gene transfer to about 30% of cells, but they did not reach the inner cellular mass within the islet core. Using the whole-pancreas perfusion protocol, we demonstrate that at least in rodent models the centrally located insulin-producing cells can be transduced with high efficiency, while preserving the structural integrity of the islet. Moreover, islet cell viability and function are not impaired by this procedure. CONCLUSIONS/INTERPRETATION: These results support the view that perfusion-based transduction protocols may significantly improve the yield of successfully engineered primary insulin-producing cells for diabetes research.

Adenoviridae↗

PubMed2006

Carbon monoxide and pancreatic islet blood flow in the rat: inhibition of haem oxygenase does not affect islet blood perfusion.

OBJECTIVE: To determine whether carbon monoxide, a known gaseous vasorelaxator, affects pancreatic islet blood flow in rats. MATERIAL AND METHODS: Sprague-Dawley rats were anaesthetized with thiobutabarbital and injected intravenously with the haem oxygenase inhibitor tin-protoporphyrin IX dichloride (SnPP; 4, 10 or 20 mg/kg body-weight). After 15 min, blood flow measurements were performed using a microsphere technique. RESULTS: There was a slight increase in mean arterial blood pressure with the highest dose of SnPP. No effects on total pancreatic, islet, duodenal, colonic, renal or adrenal blood flow were seen with any of the applied doses. CONCLUSIONS: The findings of this study suggest that the haem oxygenase-carbon monoxide system is likely to be of limited importance in the regulation of blood perfusion to the pancreas, the islets of Langerhans or any of the other studied organs.

Animals↗

PubMed2006

Lymphatic vessels in pancreatic islets implanted under the renal capsule of rats.

Transplantation of pancreatic islets necessitates an engraftment process, including revascularization of the graft. Studies of graft vasculature have demonstrated that islets become revascularized during the first post-transplant week through an angiogenic process. If this also involves lymphatic vessels is unknown. The aim of the present study was to functionally evaluate if lymphatic vessels, which are absent in endogenous islets, form after islet transplantation. To achieve this, inbred Wistar-Furth rats were transplanted with 250 syngeneic islets under the renal capsule. Intra-vital microscopy of the graft in combination with interstitial injection of Evans Blue was performed 1 week, 1 month or 9-12 months later. In all animals studied, there was drainage through intra-graft lymphatic capillaries emptying into larger lymphatic vessels associated with the renal capsule. The number was slightly lower 1 week post-transplantation. Most of the lymphatic capillaries were present in the graft stroma, rather than interspersed among the endocrine cells. In some animals, we were able to demonstrate dye in regional lymph nodes. We conclude that unlike endogenous islets, islet grafts develop a lymphatic drainage. Its functional importance and characteristics remain to be established. However, it can be speculated that immune reactions may be facilitated by the presence of lymphatic vessels.

Animals↗

PubMed2006

Islets transplanted intraportally into the liver are stimulated to insulin and glucagon release exclusively through the hepatic artery.

Not much is known about the physiology of intraportally transplanted islets. One reason for this is that it is difficult to study such islets, since they are scattered throughout the liver. We employed a perfusion technique to characterize the functional properties of syngeneic intrahepatic 1-month-old islet grafts, and compared them to islets transplanted beneath the kidney capsule, as well as native islets. The cellular composition of the islet grafts was also examined. Glucose and arginine administered through the hepatic artery, but not through the portal vein, induced insulin release from the intraportally implanted islets. Moreover, arginine, only when administered through the hepatic artery, induced glucagon release from the same islets. The first phase of glucose-stimulated insulin release from both islets transplanted to the liver and kidney was delayed, and less prominent when compared to the pancreas. Intraportally transplanted islets contained fewer glucagon-positive cells than islets transplanted to the kidney and native islets. Our findings demonstrate that intraportally transplanted islets respond with insulin and glucagon to secretagogues, but only when stimulated through the hepatic artery. Whether intrahepatic islets may sense other substances than glucose or arginine occurring in high concentrations in the portal vein following intestinal uptake remains to be studied.

Animals↗

PubMed2005

Placental dysfunction in Suramin-treated rats--a new model for pre-eclampsia.

Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of placental dysfunction and pre-eclampsia. This study was carried out to evaluate if inhibited angiogenesis by Suramin injections in early pregnancy may cause a condition resembling pre-eclampsia in rats. Rats of two different Sprague-Dawley strains, U and H, were given intraperitoneal injections of Suramin or saline in early pregnancy. The outcome of pregnancy was evaluated on gestational day 20. Suramin injections caused increased blood pressure and decreased renal blood flow in the U rats. In both rat strains Suramin decreased the placental blood flow and caused fetal growth retardation. In both strains the placental concentration of the isoprostane 8-epi-PGF2alpha was increased, indicating oxidative stress. The serum concentration of Endothelin-1 was increased in the U rats. The U strain had a lower basal placental blood flow, and the effects of Suramin were more pronounced in this strain. We conclude, that Suramin injections to pregnant rats cause a state of placental insufficiency, which partly resembles human pre-eclampsia. The induction of this condition is at least partly mediated by oxidative stress, and is subject to varied genetic susceptibility.

Angiogenesis Inhibitors↗

PubMed2005

Neuronal nitric oxide synthase and splanchnic blood flow in anaesthetized rats.

AIMS: To evaluate to what extent the neuronal form of constitutive nitric oxide synthase (nNOS) contributes to the blood perfusion of splanchnic organs, including the islets of Langerhans. METHODS: The nNOS inhibitor 7-nitroindazole (300 mg kg(-1) i.p.) was administered to anaesthetized Sprague-Dawley rats, some of which were pre-treated with the ganglionic blocker hexamethonium (20 mg kg(-1) i.v.) The blood perfusion of the splanchnic organs, including the pancreatic islets was then measured with a microsphere technique. RESULTS: Nitroindazole decreased total pancreatic, duodenal and renal blood flow, whereas pancreatic islet, colonic and adrenal blood flows were unchanged. A slight increase in mean arterial blood pressure was seen after nitroindazole treatment. Nitroindazole did not affect blood glucose or serum insulin concentrations. In separate experiments, hexamethonium affected none of the studied blood flow values, suggesting that the effects of nNOS-inhibition were not mediated from the nervous system. CONCLUSION: Nitric oxide derived from the activity of nNOS contributes to the blood perfusion in the upper portions of the gastrointestinal tract, viz. the parts supplied by the cranial mesenteric artery, and the kidneys, whilst no effects are seen on colonic or adrenal blood flow. Pancreatic islet blood flow was unaffected by nNOS inhibition, thereby suggesting that NO derived from the other isoforms of NOS maintains the high basal islet blood perfusion.

Anesthesia, General↗

PubMed2005

Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis.

BACKGROUND: Intermittent allergic rhinitis (IAR) results from interactions between a large number of pro- and anti-inflammatory mediators. Little is known about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous analysis of the whole transcriptome in a sample. OBJECTIVE: To identify anti-inflammatory transcripts in nasal fluid cells from patients with IAR during season and from healthy controls. METHODS: Nasal lavage fluids were obtained from 15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy controls. RNA was extracted from the nasal fluid cells and pooled into one patient- and one control pool. These were analysed with DNA microarrays containing more than 44,927 genes and variants. RESULTS: Seventeen thousand three hundred and fifty three genes were expressed in the controls and 17 928 in the patients. One thousand five hundred and seventy nine of the genes had higher expression in patients than in controls, and 1570 had lower expression in patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory and two were anti-inflammatory. These genes regulated key steps of inflammation, ranging from influx of leukocytes to immunoglobulin production. By comparison, out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were anti-inflammatory. The anti-inflammatory gene that decreased most in expression in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The nasal fluid concentrations of uteroglobin protein were significantly lower in patients than in controls, 5.43+/-1.53 and 12.93+/-2.53 ng/mL, respectively (P<0.05). CONCLUSION: IAR is associated with decreased expression of uteroglobin and other anti-inflammatory genes.

Adolescent↗

PubMed2004

Assessment of environmental tobacco smoke exposure: urinary cotinine concentrations in children are strongly associated with the house dust concentrations of nicotine at home.

In the present study the possibility of using nicotine in house dust as an index of environmental tobacco smoke (ETS) exposure was evaluated in an environmental investigation of 23 children with asthma. A standardized procedure for house dust sampling of nicotine with a filter holder connected to a vacuum cleaner, for a defined time and area was developed (F-nicotine). Also, house dust sampling was carried out from the vacuum cleaner bags of the homes (VC-nicotine). There was a larger variation in VC-nicotine (13-655, median 66 microg/g) compared with F-nicotine (15-393 median 156 microg/g). There were statistically significant associations between an inquiry data based ETS exposure index on the one hand, and urinary cotinine concentrations in children (U-cotinine), F-nicotine and VC-nicotine of their homes, on the other. The strong correlation between U-cotinine and F-nicotine (rs = 0.93; P < 0.0001) indicates that the new standardized house dust sampling method should be useful in ETS exposure assessment. However, further validation by a larger sample size with repeated measurements in the same homes is needed.

Adolescent↗

PubMed2004

Polymerized alpha-antitrypsin is present on lung vascular endothelium. New insights into the biological significance of alpha-antitrypsin polymerization.

AIMS: The damage to lung tissue in chronic obstructive pulmonary disease (COPD) may involve the progressive loss of pulmonary vascular endothelial cells. Endothelial binding of alpha1-antitrypsin (alpha1-AT) derived from plasma has been identified, and alpha1-AT deficiency is a known genetic risk factor associated with alpha1-AT polymerization and COPD development. Therefore, in the present study we aimed to investigate if alpha1-AT is present on the lung vascular endothelium, and if it is in a polymeric form. METHODS AND RESULTS: Postmortem paraffin-embedded tissue specimens from 15 COPD (chronic bronchitis and emphysema) cases with and without Z alpha1-AT (Glu342Lys) deficiency and from 10 cases without signs of COPD were studied. Immunohistochemistry was performed using the streptavidin-biotin method with a monoclonal ATZ11 antibody specific for polymeric alpha1-AT, and polyclonal antibodies against human alpha1-AT and neutrophil elastase. Vascular endothelium showed intense staining for alpha1-AT with the ATZ11 antibody in all cases; however, intensity of staining in patients with alpha1-AT deficiency was greater. No endothelial staining was observed with the anti-elastase antibody. CONCLUSIONS: This is the first demonstration that alpha1-AT bound to the vascular endothelium of lungs is in a polymeric form, which also suggests a possible previously unknown role for polymeric alpha1-AT in vivo.

Endothelium, Vascular↗

PubMed2004

Pancreatic islet blood flow during pregnancy in the rat: an increased islet mass is associated with decreased islet blood flow.

Increased blood perfusion of pancreatic islets is seen during various conditions of increased demand for insulin secretion. Pregnancy confers an increased need for insulin secretion, met by increased islet mass and volume as well as a decreased threshold for glucose-induced insulin secretion. In the present study, whole pancreatic and islet blood flow were studied with a microsphere technique in Wistar rats on days 15, 18 and 20 of pregnancy and days 2 and 7 post-partum. There were no changes in total pancreatic blood flow during pregnancy and the first post-partum week. Total blood perfusion through islet tissue expressed as flow per weight of whole pancreas was higher at day 15 of pregnancy. When islet blood flow was expressed per gram of islet tissue there was a decrease at day 18 of pregnancy. This decrease of islet blood flow was concomitant to a short-lived increase of the islet mass at the end of pregnancy. We conclude that upregulation of insulin output during late pregnancy does not specifically include increased net blood perfusion through the islets. One possible reason for this might be lack of synchronization between the proliferation of endocrine cells and angiogenesis, resulting in a relative decrease in islet vascular density in the islets.

Animals↗

PubMed2003

Hypoglycaemia induces decreased islet blood perfusion mediated by the central nervous system in normal and Type 2 diabetic GK rats.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the effects of induced hypoglycaemia on pancreatic-islet blood flow in normal rats and in the GK rat, an animal model of Type 2 diabetes which normally has an increased islet blood perfusion. METHODS: A 50% reduction in blood glucose concentrations was achieved by intravenous administration of a rapidly acting insulin (15 IU/kg body weight). Blood flows were measured by a non-radioactive microsphere technique. RESULTS: A pronounced decrease in islet blood flow was observed in all animals, but preferentially in the Type 2 diabetic GK rats. When a similar dose of insulin was given to whole-pancreas transplanted rats only islet blood flow in the native pancreas was decreased, whereas that of the transplanted, i.e. denervated, pancreas was unchanged. Administration of 2-deoxy-D-glucose, which induces intracellular glucopenia especially in neurons, also decreased islet blood flow despite a systemic hyperglycaemia. CONCLUSION/INTERPRETATION: Hypoglycaemia leads to a preferential decrease in pancreatic-islet blood perfusion. The effect is probably mediated by the central nervous system, since 2-deoxy D-glucose-induced neuronal glucopenia caused a similar decrease in blood flow. The effects of islet blood flow are not likely to be mediated by nervous stimulation of the adrenal glands, with an associated release of catecholamines, because the transplanted pancreas was not affected by hypoglycaemia. The decreased islet blood perfusion could possibly diminish the output of insulin from the islets, thereby preventing a further decrease in blood glucose concentrations.

Animals↗

PubMed2003

Anomalies of subjective experience in schizophrenia and psychotic bipolar illness.

OBJECTIVE: Contemporary psychopathology, as a result of behaviourally dominated epistemological stance, downplays anomalies of the patient's subjectivity. This neglect has probably deleterious consequences for research in the causes and the boundaries of the schizophrenia spectrum conditions. The purpose of this study is to explore frequency of qualitative, not-yet-psychotic, anomalies of subjective experience in patients with residual schizophrenia and psychotic bipolar illness in remission. METHOD: The patients were examined with the Danish version of the Bonn Scale for the Assessment of Basic Symptoms (BSABS). Anomalies of experience were condensed into rational scales with good internal consistencies. RESULTS: Diagnosis of schizophrenia was associated with elevated scores on the scales measuring perplexity (loss of immediate meaning), disorders of perception, disorders of self-awareness, and marginally so, disorders of cognition. CONCLUSION: These findings, in conjunction with those from other, methodologically similar studies, suggest that certain anomalies of subjective experience aggregate significantly in schizophrenia. These experiential anomalies appear to be relevant for early differential diagnosis and therefore potentially useful in the preonset detection of the schizophrenia spectrum illness.

Adult↗

PubMed2002

Graft vascular function after transplantation of pancreatic islets.

Endogenous pancreatic islets have a dense glomerular-like angioarchitecture, which ensures an optimal delivery of oxygen and nutrients to the islet cells, provides signals from other cells in the body and disposes secreted hormones. Transplantation of isolated islets means that their vascular connection is interrupted. The islet grafts therefore depend upon endothelial cells and microvessels originating in the implantation organ for derivation of a new vascular system. A re-establishment of islet blood-flow occurs within 7-14 days after transplantation, mainly through vascular sprouting. The newly formed blood vessels acquire the morphological characteristics of those in endogenous islets. In intraportally transplanted islets to the liver, the islets become revascularized almost exclusively from tributaries to the hepatic artery. Exocrine contamination of the transplanted islets could hamper the revascularization process, whereas neither cryopreservation nor immunosuppressive drugs like cyclosporin, prednisolon and RS-61443 have any essential effects on the angiogenesis. Investigators have noticed improvements in islet graft survival and function by means of basic fibroblast growth factor (bFGF), acidic FGF and endothelial cell growth factor exposure of the grafts. The functional properties of transplanted islets are largely unknown, but evidence from experimental islet transplantation suggests that both the blood perfusion and the tissue oxygen tension of the grafted islets are chronically decreased, indicating an insufficient vascular system. In order to achieve optimal condition for survival and function of transplanted beta cells, it is important to ascertain whether impairments in vascular function are present also after clinical islet transplantations as well.

Animals↗

PubMed2002

Unaltered oxygen tension in rat pancreatic islets despite dissociation of insulin release and islet blood flow.

The present study investigated the importance of a tightly regulated islet blood flow for an optimal oxygenation of the islet tissue during different demands for insulin release. Glucose and/or a non-specific nitric oxide synthase inhibitor (L-NNA) were infused intravenously in non-pretreated or vagotomized rats and the animals were subjected to measurements of islet blood flow, oxygen tension and serum insulin concentrations. Islet blood flow was measured using a non-radioactive microsphere technique, tissue oxygen tension was recorded with Clark microelectrodes and insulin concentrations were determined by enzyme-linked immunosorbent assay technique. Administration of L-NNA (0.3 mg kg(-1) min(-1)) for 10 min halved basal islet blood flow, but did not affect serum insulin concentrations. Glucose administration (10 mg kg(-1) min(-1)) induced a marked increase in islet blood flow, which could be prevented by vagotomy or L-NNA. The serum insulin concentrations increased in all glucose-infused animals. The islet tissue oxygen tension remained similar in all animals despite these interventions. Reasons other than oxygenation of the islet tissue must explain the normally existing tight regulation of islet blood flow.

Animals↗

PubMed2002

Socioeconomic environmental factors and hospitalization for acute bronchiolitis during infancy.

UNLABELLED: Bronchiolitis is a major cause of hospitalization during infancy. The aim of this study was to evaluate the influence of socioeconomic factors on the hospitalization of infants with bronchiolitis. All infants below 1 y of age living in the city of Malmö, Sweden, and hospitalized at the University Hospital. Malmö, owing to bronchiolitis during the years 1998 and 1999 were identified. The bronchiolitis hospitalization rates (BHRs) were determined for the infants living in each of the 10 different administrative residential areas of Malmö and correlated with socioeconomic factors (percentage of immigrants, per capita income, unemployment rate and households receiving social benefit) in the respective residential areas. The severity of the disease on admission and during hospital care was assessed by comparing oxygen saturation, days with supplemental oxygen and length of stay. BHR varied more than fourfold between the 10 residential areas. BHR varied significantly with per capita income and the percentage of immigrants. Infants living in the area with the highest social burden were hospitalized almost twice as often as those from the rest of the city, but the severity of disease was similar. CONCLUSION: The association between socioeconomic factors and hospitalization indicates that these factors may have a significant influence on the hospitalization rate in bronchiolitis during infancy.

Acute Disease↗

PubMed2001

The H2-Ab gene influences the severity of experimental allergic encephalomyelitis induced by proteolipoprotein peptide 103-116.

Immunization of H2(p) and H2(q) congenic C3H mouse strains with the PLP 103-116 peptide elicited two distinct experimental allergic encephalomyelitis (EAE) disease courses. C3H.Q (H2(q)) mice developed an acute-phase disease with classical ascending paralytic signs whereas C3H.NB (H2(p)) developed a highly variable disease course with symptoms originating from CNS above the spinal chord. C3H.Q lacks functional H2-E molecules and share H2-Aalpha with C3H.NB. To examine if the differences found at positions 85, 86, 88, and 89 in the Abeta-chains account for disease susceptibility, H2(q) mice were made transgenic with the Ab(p) gene. The Ab(p)-transgenic mice on the C3H.Q background developed a more severe disease course, demonstrating the importance of class II. However, the onset was not affected and the disease showed a classical ascending paralysis similar to the C3H.Q suggesting that the observed brain symptoms were related to nonclass II genes. Inhibition studies performed on affinity purified MHC class II molecules indicated that the PLP 103-116 peptide bound to A(p) with slightly higher affinity than to A(q). Both A(q) and A(p) formed long-lived stable complexes (t(1/2)>24 h) with the PLP 103-116 peptide, but a higher amount of the peptide was loaded on to A(p) compared with A(q). An F2 gene segregation experiment, in which the low PLP 103-116 binding A(r) molecule and the high binding A(p) molecule could be compared for the influence on the disease susceptibility, indicated a role for both peptide binding affinity and non-MHC genes. Based on our results, we conclude that the H2-Ab gene controls severity of EAE but not necessarily the onset or type of disease course and that affinity of the disease-promoting peptide for the class II molecule is a critical pathogenic factor.

Animals↗

PubMed2001

Microcirculation of human pancreatic islets transplanted under the renal capsule of nude mice.

BACKGROUND: The aim was to measure the capillary blood pressure in transplanted human islets. METHODS: Human islets were isolated at the Central Unit of the beta-cell Transplant in Brussels, Belgium. After transport to our laboratory, the islets were implanted under the renal capsule of normoglycemic nude mice. Two weeks later the capillary and venous blood pressures in the islet graft and adjacent renal parenchyma were measured with a micropuncture technique. RESULTS: Capillary blood pressure was approximately 5-8 mmHg in both graft and renal capillaries: twice as high as in native islets. Venous blood pressures were similar (4-5 mmHg) in the veins draining the graft and in the renal interlobular veins. All veins leading from the graft emptied into the renal parenchyma, that is, into interlobular veins. CONCLUSIONS: The capillary hypertension seen in transplanted human islets is probably necessary to secure adequate drainage through the renal veins. Whether this contributes to the poor results of long-term islet graft survival is unknown.

Adolescent↗

PubMed2001

Reinnervation of syngeneic pancreatico-duodenal grafts in rats.

BACKGROUND: Knowledge on the reinnervation of transplanted organs is scarce, and the aim of the study was therefore to evaluate to what degree syngeneic pancreas grafts were reinnervated in rats. METHODS: Syngeneic pancreatico-duodenal transplantations were performed in normoglycemic Wistar-Furth rats. Native and transplanted pancreas and duodenum were removed 4 or 40 weeks after implantation, and processed for indirect immunofluorescence using antibodies directed against vasoactive intestinal peptide, substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), or the general neuronal marker protein gene product 9.5. RESULTS: Four weeks after transplantation a moderate to rich number of protein gene product 9.5-positive nerve fibers were found homogeneously distributed through the pancreas, probably representing the intrapancreatic nervous system, because the grafted pancreas lacked both a sympathetic (TH/NPY) and sensory (SP/CGRP) innervation 4 weeks after implantation. In a few of the animals there was a marked increase in SP-immunoreactive nerves (lacking CGRP), most conspicuous in the duodenal portion, both 4 and 40 weeks after transplantation probably secondary to a chronic pancreatitis. The fibers seemed to emanate from intrapancreatic ganglia and possibly also from enteric neurons in adjacent parts of the duodenum. A few scattered vasoactive intestinal peptide-containing nerve fibers probably also emanating from local ganglia could be seen throughout the grafted pancreas both 4 and 40 weeks after transplantation. At 40 weeks after transplantation sympathetic (TH- and NPY-positive) nerve fibers were regularly seen, whereas CGRP-positive nerve fibers were still virtually lacking in the pancreas. To trace the origin of the ingrowing nerve fibers, the tracer True Blue was injected into the grafted pancreas of some rats 38 weeks after transplantation, i.e., 2 weeks before killing. True Blue-labeled nerve cell bodies were numerous in the celiac ganglion (presumably sympathetic nerves) and few in dorsal root ganglia (sensory nerves). CONCLUSIONS: The data suggest that the transplanted rat pancreas becomes reinnervated by mainly sympathetic nerve fibers.

Animals↗