Biomedical subjects

J Larsson

Publications and source records attributed to J Larsson.

At least 55 records · Page 3Linked to original sources

PubMed2000

The intracellular mechanism of insulin resistance in pancreatic cancer patients.

The diabetes that frequently occurs in pancreatic cancer patients is characterized by profound peripheral insulin resistance. The intracellular mechanism of this insulin resistance was investigated in skeletal muscle biopsies from pancreatic cancer patients with or without diabetes and control subjects. Insulin receptor (IR) binding, tyrosine kinase activity, IR messenger RNA (mRNA), IR substrate-1 content, GLUT-4, and GLUT-4 mRNA content were all normal in pancreatic cancer patients. In contrast, multiple defects in glycogen synthesis were found in pancreatic cancer patients, especially in those with diabetes. Glycogen synthase I activity, total activity, and mRNA levels were significantly decreased in pancreatic cancer patients compared with controls. The fractional velocity of glycogen synthase was decreased only in the diabetic pancreatic cancer group. Glycogen phosphorylase a and b activities were increased in diabetic pancreatic cancer patients, but glycogen phosphorylase mRNA levels were not significantly different. The insulin resistance associated with pancreatic cancer is associated with a post-IR defect, which impairs skeletal muscle glycogen synthesis and glycogen storage.

Blotting, Western↗

PubMed2000

Gastrointestinal growth factors and pancreatic islet hormones during postoperative IGF-I supplementation in man.

Insulin-like growth factor-I (IGF-I) has been demonstrated to exert a nitrogen sparing effect, both experimentally and in patients after abdominal surgery. IGF-I is a major mediator for the anabolic effects of growth hormone (GH). Whether elevated circulating IGF-I levels are the sole mediator of the anabolic effects following GH has not been clarified. IGF-I influences glucose metabolism, both through its own specific receptor and by activating the insulin receptor, and has also been proposed to influence pancreatic islet secretion directly. In the present study, the postoperative effects of IGF-I on plasma levels of other gastrointestinal and pancreatic islet hormones and growth factors were measured in patients after abdominal surgery. Fifteen patients who were candidates for large bowel resection were randomly divided into two groups: IGF-I-treated (n=8) and placebo-treated (n=7). The IGF-I group received daily two s.c. injections of human recombinant IGF-I (80 microg/kg body weight) for five days, beginning on the morning of the first postoperative day. The other group received placebo injections. Fasting plasma levels of gastrointestinal growth factors (epidermal growth factor, transforming growth factor-alpha, IGF-II), gastrointestinal hormones (gastrin, enteroglucagon, peptide YY), and islet hormones (insulin, islet amyloid polypeptide (IAPP) and pancreatic glucagon) were determined by RIA preoperatively and after five days of treatment. No significant effects of IGF-I on other growth factors or gastrointestinal hormones were seen. A marked increase in plasma insulin postoperatively compared with the preoperative levels (42+/-3 vs 61+/-5 pM, P<0.05) was seen in the placebo group, whereas the postoperative levels in the IGF-I-treated patients remained unchanged (44+/-3 vs 45+/-4 pM). A similar pattern was observed for IAPP and cortisol concentrations. No differences in glucagon concentrations were seen. In conclusion, these results suggest that IGF-I does not influence production of other gastrointestinal hormones thought to be involved in alimentary growth or pancreatic glucagon. In contrast, IGF-I caused a marked reduction of insulin and IAPP secretion. The inhibition of beta-cell secretion could be direct or, alternatively, could involve an improvement in postoperative insulin resistance, perhaps by reducing serum cortisol.

Aged↗

PubMed1999

The prothrombin gene G20210A mutation and the platelet glycoprotein IIIa polymorphism PlA2 in patients with central retinal vein occlusion.

The prothrombin gene G20210A mutation and the platelet glycoprotein IIIa polymorphism PlA2 have been shown to be associated with thromboembolic disease. We wondered if mutations were overrepresented in patients with central retinal vein occlusion. We studied 129 consecutive patients with a history of central retinal vein occlusion. We analysed for the prothrombin gene G20210A mutation and the platelet glycoprotein IIIa polymorphism PlA2 and compared the results to controls with no history of thrombosis. For the platelet glycoprotein IIIa polymorphism PlA2, 69% were normal, 26% were heterozygous, and 5% were homozygous. For the G20210A prothrombin mutation, 97% were normal and 3% were heterozygous. Neither the prothrombin gene G20210A mutation nor the platelet glycoprotein IIIa polymorphism PlA2 seem to be associated with central retinal vein occlusion.

Adult↗

PubMed1999

Particles binding beta(2)-integrins mediate intracellular production of oxidative metabolites in human neutrophils independently of phagocytosis.

Complement-opsonised particles are readily ingested by human neutrophils through a complement receptor-mediated process leading to phagolysosome fusion and production of oxidative metabolites. To investigate the complement receptor 3 (CR3)-associated signal system involved, cells were challenged with protein A-positive, heat-killed Staphylococcus aureus to which antibodies with specificity for the subunits of the beta(2)-integrins, i.e. anti-CD11b (the alpha subunit of CR3) and anti-CD18 (the beta subunit of CR3), were bound through their Fc moiety. Despite not being ingested by the neutrophils, the surface associated anti-CD18- and anti-CD11b-coated particles were able to activate the neutrophil NADPH-oxidase. Also anti-CD11a- (the alpha subunit of LFA-1) and to a lesser extent anti-CD11c- (the alpha subunit of CR4) coated particles were able to trigger the NADPH-oxidase. The NADPH-oxidase was activated without extracellular release of reactive oxygen species. The activity was inhibited by cytochalasin B, suggesting a necessary role for the cytoskeleton in the signalling pathway that activates the oxidase. We show that particle-mediated cross-linking of beta(2)-integrins on the neutrophil surface initiates a signalling cascade, involving cytoskeletal rearrangements, leading to an activation of the NADPH-oxidase without phagosome formation or extracellular release of reactive oxygen species.

Antibodies↗

PubMed1999

[The diabetic foot. Optimal prevention and treatment can halve the risk of amputation].

Almost half of all lower leg amputations are performed in patients with diabetes. In over 70 per cent of these cases, amputation is precipitated by progression of foot ulceration to deep gangrenous infection. Most foot ulcers are preceded by trauma, usually due to ill-fitting shoes, and are precipitated by sensory motor neuropathy with varying degrees of peripheral vascular disease. The Swedish Medical Research Council and the Swedish Institute for Health Services Development arranged a conference on diabetic foot problems in April 1998, the purpose of which was to arrive at a consensus regarding the prevention and management of diabetic foot. It was concluded that a satisfactory multidisciplinary approach should include regular control of feet and footwear, preventive foot care (education, footwear, chiropody), continuous follow-up of high-risk feet, and early recognition of revascularisation. Continuous registration of amputation, irrespective of type, cause and site, might substantially reduce the amputation rate among diabetics. Were such an approach to reduce the incidence of diabetes-related amputation by 50 per cent, annual costs for the management of diabetic foot in Sweden would be reduce by SEK 400 million (the value of improved quality of life not taken into consideration).

Amputation, Surgical↗

PubMed1999

Subacute versus delayed reconstruction of the anterior cruciate ligament in the competitive athlete.

The objective of this study was to compare the function and activity level in patients with anterior cruciate ligament injuries, who participated in competitive sports (Tegner activity level > or = 7) and underwent a reconstruction of the anterior cruciate ligament, either subacute (2-12 weeks, group I) or late (12-24 months, group II) after the injury. The patients in group I (n = 97) were comparable with those in group II (n = 103) in terms of gender, age, preinjury activity level, and the reconstruction technique. At the final follow-up (2-5.5 years after the operation), the Lysholm score, the IKDC evaluation system and the one-leg-hop test revealed no differences between the groups. There were also no differences between the groups in terms of the patients' subjective evaluation or expectations. The Tegner activity level at follow-up was 8 (range 2-10) in group I and 6 (range 2-9) in group II (P = 0.0001). The same thing was found in terms of the desired Tegner activity level, which was 9 (range 4-9) in group I and 7 (range 3-10) in group II (P = 0.0002). The KT-1000 laxity meter revealed a total side-to-side difference of 1.5 mm (-3.5-8.5) in group I and 1.5 mm (-3.5-7) in group II (NS). Associated meniscal surgery between the index injury and the reconstruction, or during the reconstruction, was performed in 37/97 (38%) of the patients in group I and 59/103 (57%) of the patients in group II (P < 0.01). This study revealed that competitive athletes who underwent reconstruction at a subacute stage after the anterior cruciate ligament injury had a higher activity level 2-5.5 years after the index operation, as well as a higher desired level of activity compared to athletes who had the reconstruction delayed by 12-24 months. Furthermore, meniscal injuries were significantly more frequent if the reconstruction was delayed.

Adolescent↗

PubMed1999

Analysis of subjective, objective and functional examination tests after anterior cruciate ligament reconstruction. A follow-up of 527 patients.

This study included 527 patients (178 female and 349 male) with unilateral anterior cruciate ligament (ACL) rupture who underwent arthroscopic ACL reconstruction using bone-patellar tendon-bone autograft and interference screw fixation. The follow-up examination was performed by independent observers at a median of 38 (21-68) months after the index operation. At the follow-up, the Lysholm score was 86 (14-100) points, the Lysholm instability subscore was 22 (0-25) points and the Lysholm pain subscore was 19 (0-25) points. The Tegner activity level was 6 (1-10). The one-leg-hop test was 91 (0-167)% of the non-injured knee. The difference in the anterior side-to-side laxity as measured with the KT-1000 arthrometer at 89 Newton (N) was 1.5 (-5-13) mm and the total KT-1000 side-to-side difference at 89 N was 2 (-7-11) mm. Using the International Knee Documentation Committee (IKDC) evaluation system, 177 (33.6%) patients were classified as normal (group A), 211 (40%) as nearly normal (group B), 109 (20.7%) as abnormal (group C) and 30 (5.7%) as severely abnormal (group D). The highest correlation coefficients were recorded between the IKDC evaluation system and the Lysholm score (p = 0.66), the patients' subjective evaluation (p = 0.53), the Tegner activity level (p = 0.34), all the laxity tests (p > or = 0.34) and the one-leg-hop test (p = 0.28). The resumption of sporting activities and work as evaluated by the Tegner activity level correlated with the patients' subjective evaluation (p = 0.34) but did not correlate with the laxity tests, i.e., the manual Lachman test (p = -0.06) and the total and anterior KT-1000 tests (p = -0.06). Furthermore, none of the laxity tests correlated with the functional tests or the patients' subjective evaluation. We conclude that the IKDC evaluation system is a reliable and useful tool for evaluating the post-operative outcome after an ACL reconstruction.

Adolescent↗

PubMed1999

MHC expression in syngeneic and allogeneic retinal cell transplants in the rat.

BACKGROUND: The major histocompatibility complexes, MHC class I and II, are found only sparsely or not at all in the retina. Since the eye is immunoprivileged, we decided to investigate how the MHC class I and II antigens were influenced by a retinal transplant and whether this could be correlated to rejection of the transplant. METHODS: Fetal neural retinas of Sprague-Dawley (SD) rats were implanted in the subretinal space of adult Lewis and SD rats. After 5 weeks the retinas and the transplants were evaluated with antibodies against MHC class I and II antigens as well as microglia. RESULTS: In the syngeneic transplants no upregulation of MHC class I antigen was seen and no MHC class II-positive cells could be detected. In the allogeneic transplants, on the other hand, there was marked upregulation of MHC class I antigen. Numerous MHC class II antigen-positive cells were seen in the subretinal transplant but also in the host retina. CONCLUSION: Allogeneic retinal transplants seem to grow and thrive just as well as syngeneic transplants, but in the former there is considerable upregulation of MHC expression. Our interpretation of these results is that the allogeneic transplants are recognized as nonself, but that there is also something that modifies this reaction of the immune system at this level, preventing the rejection that would normally ensue.

Animals↗

PubMed1999

Glutamine effects on permeability and ATP content of jejunal mucosa in starved rats.

INTRODUCTION: Starvation induces an increase in intestinal permeability that can be of importance to intestinal integrity. Glutamine is the principal energy source for intestinal enterocytes and is considered essential for gut metabolism, structure and function. The aim of this study was to investigate whether glutamine could improve the ATP content of the mucosa of starved rats and attenuate the permeability perturbation during incubation in vitro in Ussing chamber. METHODS: Segments of jejunum from rats starved for 48 h were mounted in Ussing chambers. Glutamine was added to Krebs-buffer at 0.6mM, 3mM, 6mM and 30mM concentrations on the mucosal side. Cr-EDTA permeation, ATP content of the epithelium mucosa and electrophysiology were studied during 180 min of incubation in Ussing chambers. RESULT: These was a negative linear correlation between ATP content and(51)Cr-EDTA permeability in stripped mucosa. ATP content was reduced in all groups during the experiment. When 30 mM glutamine was added on the mucosal side there was an increase in(51)Cr-EDTA permeability (P< 0.001). There was no effect of glutamine on transepithelial resistance but higher concentrations of glutamine (>3mM) significantly increased the short circuit current. CONCLUSION: Supplementing glutamine to the mucosal side in the Ussing chamber led to an increase in ion pump activity and to an increase in paracellular permeability at the 30mM glutamine concentration. Glutamine did not restore the intracellular ATP level. The increase in permeability was inversely correlated to the mucosal ATP content.

Adenosine Triphosphate↗

PubMed1999

Early response of ornithine decarboxylase activity and energy metabolism to postsurgery refeeding in rat small intestine.

INTRODUCTION: Enterocyte proliferation and cellular energy status are important to intestinal integrity after starvation and trauma. The proliferative response to nutrients is expressed in the activity of ornithine decarboxylase (ODC), but ODC activity and ATP level in the intestinal mucosa the first hours after surgery and immediate refeeding are not known. METHODS: Male Wistar rats (240-280 g) were starved for 48 h and submitted to laparotomy with distal ileal transection, gastrostomy and jejunal instillation of either enteral formula or saline. The ODC activity and ATP content of the jejunal mucosa were analysed in samples taken at 1, 2, 4 and 6 h after surgery. RESULTS: ODC activity increased and reached the highest peak at 2 h in the refed animals. ATP concentration and energy charge of jejunal mucosa were significantly reduced 6 h after surgery compared to initial levels, but there were no differences between animals that were refed or not. Intestinal transection did not stimulate ODC activity. CONCLUSION: ATP levels in intestinal mucosa decreased after surgery, and early enteral feeding did not seem to prevent this decrease during the first 6 h. Refeeding immediately after surgery elicits an early but transient increase of ODC activity in rat jejunal mucosa.

Adenosine Triphosphate↗

PubMed1999

Activated protein C resistance and anticoagulant proteins in young adults with central retinal vein occlusion.

BACKGROUND: Central retinal vein occlusion is a disease that is most common in old people, and often associated with atherosclerosis, hypertension, diabetes or glaucoma. Since these diseases are much less evident in young people, we wanted to investigate the prevalence of disorders in the most common anticoagulant proteins in a group of young patients with central retinal vein occlusion. METHODS: 37 consecutive patients younger than 50 years and with a history of central retinal vein occlusion, were analysed for deficiencies of natural inhibitors of coagulation (protein C, S, and antithrombin III), plasminogen, resistance to activated protein C, and the presence of anticardiolipin or lupus anticoagulants. RESULTS: Anticoagulant protein deficiencies were found in 4 patients (11%) and activated protein C resistance in 7 patients (19%). Anticardiolipin or lupus anticoagulants were not found in the patients. CONCLUSION: Activated protein C resistance and anticoagulant protein deficiencies seem to be important factors to the etiology to central retinal vein occlusion in young patients.

Activated Protein C Resistance↗

PubMed1999

Neuronal correlates of real and illusory contour perception: functional anatomy with PET.

Illusory contours provide a striking example of the visual system's ability to extract a meaningful representation of the surroundings from fragmented visual stimuli. Psychophysical and neurophysiological data suggest that illusory contours are processed in early visual cortical areas, and neuroimaging studies in humans have shown that Kanizsa-type illusory contours activate early retinotopic visual areas that are also activated by real contours. It is not known whether other types of illusory contours are processed by the same mechanisms, nor is it clear to what extent attentional effects may have influenced these results, as no attempt was made to match the salience of real and illusory stimuli in previous imaging studies. It therefore remains an open question whether there are any brain regions specifically involved in the perception of illusory contours. To address these questions, we have used 15O-butanol positron emission tomography (PET) and a novel kind of illusory contour stimulus that is induced only by aligned line ends. By employing a form discrimination task that was matched for attention and stimulus salience across conditions we were able to directly contrast perception of real and illusory contours. We found that the regions activated by illusory contour perception were the same as those activated by real contours. Only one region, located in the right fusiform gyrus, was significantly more strongly activated by perception of illusory contours than by real contours. In addition, a principal component analysis suggested that illusory contour perception is associated with a change in the correlation between V1 and V2. We conclude that different kinds of illusory contours are processed by the same cortical regions and that these regions overlap extensively with those involved in processing of real contours. At the regional level, perception of illusory contours thus appears to differ from perception of real contours by the degree of involvement of higher visual areas as well as by the nature of interaction between early visual areas.

Adult↗

PubMed1999

Effects of starvation and bowel resection on paracellular permeability in rat small-bowel mucosa in vitro.

BACKGROUND: Maintenance of intestinal integrity is essential after major abdominal surgery in malnourished subjects. The purpose of this experimental study was to investigate factors affecting small-bowel mucosa permeability in vitro in the immediate postoperative period in starved rats. METHODS: Male Wistar rats were randomly placed in five groups: Controls, Anesthesia, Resection, Starvation, and Starvation + resection. Controls consisted of fed rats. Anesthesia was induced intraperitoneally with xylazine and ketamine. Resection was 5 cm of the mid-jejunum, and the starvation period was 48 h. Two hours after surgery stripped mucosal segments from the jejunum and the ileum were mounted in Ussing chambers, and the transmucosal permeation of 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and dextran (40,000 Da) was studied for 120 min while electrophysiology was monitored. RESULTS: Starvation increased permeability to 51Cr-EDTA in both the jejunum and ileum. In the jejunum permeability was further increased by starvation + resection. Resection or anesthesia alone did not increase permeability. The villous height in the jejunum was reduced by starvation. Mucosal permeability was correlated to the change in transepithelial resistance during experiments. CONCLUSIONS: Starvation was the main cause of increased mucosal permeability in both intestinal segments of the rat, but surgical trauma had an additive effect, which was most pronounced in the jejunum.

Animals↗

PubMed1999

Early gastrointestinal regulatory peptide response to intestinal resection in the rat is stimulated by enteral glutamine supplementation.

BACKGROUND: Intestinal resection stimulates the synthesis and release of gastrointestinal peptides that regulate the growth and adaptation of the mucosa. Luminal nutrients are necessary for optimal proliferation and glutamine is the preferential nutrient to the small bowel. The interplay between glutamine and regulatory peptides could be important in treating short bowel syndrome. METHODS: 63 Sprague-Dawley rats were divided into 3 groups: resection; transection, or controls. After intestinal resection animals were orally fed either a diet without glutamine or a glutamine-supplemented diet for 2 days. Transected animals and controls without prior surgery were fed the same two diets. Epidermal growth factor (EGF), transforming growth factor-alpha, insulin-like growth factors I and II (IGF-I and IGF-II), peptide YY (PYY), and enteroglucagon were analyzed in mucosa from the proximal jejunum, distal ileum as well as in portal plasma when the animals were euthanized 72 h after surgery. RESULTS: Intestinal resection resulted in an early increase in portal plasma concentrations of PYY, EGF, enteroglucagon, and mucosal IGF-II and EGF content that were significant in glutamine-treated animals. Glutamine significantly increased PYY in portal blood after resection (p < 0.05). CONCLUSION: Glutamine could be of importance for the functional adaptation of residual small bowel mucosa by increasing PYY release.

Animals↗

PubMed1998

Somatic and germline clone analysis in mutants of the S-adenosylmethionine synthetase encoding gene in Drosophila melanogaster.

We have analysed the phenotypic consequences of homozygous mutant clones in the S-adenosylmethionine synthetase encoding gene in Drosophila melanogaster. The results suggest that SamS function is required for cell proliferation/growth in embryonic/early larval cells and during development of imaginal disc cells. Homozygous SamS germline clones can, however, develop and give rise to viable heterozygous offspring. This offspring expresses a Minute-like phenotype. We suggest that this phenotype is caused by an obstruction of the polyamine biosynthesis.

Animals↗

PubMed1998

In vitro influences between pancreatic adenocarcinoma cells and pancreatic islets.

BACKGROUND: Interactions have been found between exocrine pancreatic adenocarcinoma and islets of Langerhans. Growth of pancreatic adenocarcinoma cells can be regulated by islet hormones such as insulin and somatostatin. Conversely, dysfunction of endocrine pancreas frequently accompanies the exocrine malignancy. The mechanisms underlying these interactions have not been defined. MATERIALS AND METHODS: Human pancreatic adenocarcinoma cells (HPAF cells) were cocultured with isolated rat pancreatic islets in two-compartment wells. HPAF cells and islets cultured in separate wells served as controls. In separate experiments, HPAF cells were incubated with two concentrations of exogenous insulin, including one reflecting the levels of insulin secretion seen in the coculture experiments. RESULTS: Proliferation of HPAF cells was increased by about 50% following a 2- or 5-day incubation with pancreatic islets (P < 0.05). Coculture of HPAF cells and pancreatic islets was associated with a greater reduction in glucose concentrations (P < 0. 01) and an increase in lactate accumulation (P < 0.05) in the culture media. Insulin concentrations in the media were significantly decreased during the first 2-3 days of the coculture incubation (P < 0.05). In contrast, insulin secretion from control islets was not significantly decreased until the fifth day of the experiment. The growth of HPAF cells was stimulated by both concentrations of exogenous insulin (P < 0.05). The insulin-stimulated HPAF cells also showed an enhanced glucose consumption and lactate production (P < 0.05). CONCLUSIONS: Pancreatic islets regulate both growth and glucose metabolism of adjacent exocrine cancer cells. beta-cell-derived insulin may be one of the factors inducing these effects. Insulin release from islet beta-cells is compromised in the presence of exocrine cancer cells.

Adenocarcinoma↗

PubMed1998

Cone b-wave implicit time as an early predictor of rubeosis in central retinal vein occlusion.

PURPOSE: To investigate the predictive value of the cone b-wave implicit time in the 30-Hz flicker electroretinogram for rubeosis in the acute phase of central retinal vein occlusion. METHODS: In a prospective study, 25 patients (25 eyes) with a central retinal vein occlusion of less than 14 days' duration were examined with electroretinography and followed up for a minimum of 18 months. RESULTS: The cone b-wave implicit time in the eyes that developed rubeosis (n = 11) was more than 37.1 milliseconds and in the eyes that did not develop rubeosis (n = 14), less than 37 milliseconds (P < .00001). CONCLUSION: The cone b-wave implicit time in the 30-Hz flicker electroretinogram is a good predictor of rubeosis at an early stage in eyes with central retinal vein occlusion.

Acute Disease↗

PubMed1998

The role of glutamine, serum and energy factors in growth of enterocyte-like cell lines.

BACKGROUND: Glutamine is routinely added to most cell cultures. Glutamine has been found to be the preferential nutrient to the rapidly replicating intestinal mucosa, but whether this is a metabolic effect or due to other properties of this amino acid is not determined. To study the importance of glutamine on the growth of two enterocyte-like cell lines, the effects of depriving the media or supplementing it with glutamine were assessed in media with different serum and energy supplements. METHODS: CaCo-2 and HT-29 cells were grown in serum-free medium, with fetal bovine or synthetic serum, and with or without glucose or galactose. The glutamine content was varied between 0 and 4 mM. All growth assays were performed in triplicate by counting in a hemocytometer. RESULTS: Both cell lines were dependent of serum factors for growth, but displayed distinct requirements on glutamine supplementation. Glutamine was an obligate supplement with dose-dependent correlation to growth (r = 0.87, p < 0.01) for CaCo-2 cells cultured in synthetic, but not in fetal bovine serum. In HT-29 cells, the correlation between glutamine and growth was significant (r = 0.68, p < 0.05) only in fetal bovine serum in the absence of galactose. CONCLUSION: This study shows that glutamine has different growth stimulating effects on two enterocyte-like cell lines studied. This could reflect different modes of action of glutamine on proliferation and differentiation in an enterocyte cell population.

Animals↗