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Biomedical subjects

J Larsson

Publications and source records attributed to J Larsson.

At least 73 records · Page 4Linked to original sources

Survival and MHC-expression of embryonic retinal transplants in the choroid.

PURPOSE: To study the survival of syngenic versus allogenic embryonic retinal transplants in the choroid, and try to correlate the survival to the expression of MHC-expression and the presence of activated microglia. METHOD: Fetal neural retinas of Sprague-Dawley (SD) rats were implanted in the choroid of adult Lewis and SD rats. After 3 weeks the retina, the choroid and the transplants were examined by light microscope and evaluated with antibodies against MHC class I and II. RESULTS: Retinal transplants were found in all eyes. The transplants had one subretinal and one choroidal component. The syngenic transplants thrived in the subretinal space and formed rosettes and the choroidal components had to some extent rosette formation, though not as distinct as in the subretinal part. Almost no upregulation of MHC class I and II was seen. The allogenic transplants were totally deranged in the subretinal space as well as in the choroid. There was a marked upregulation of MHC class I, most pronounced in the transplants, but also in the host retina. Numerous MHC class II positive cells were seen in the transplants, but also in the host retina. All of these cells were dendritic and had the typical appearance of microglia. CONCLUSION: Syngenic choroidal transplants were seen to grow and thrive, whereas the allogenic transplants were rejected. There is a considerable upregulation of MHC expression in the allogenic transplants, but not in the syngenic.

Animals↗

Fluorescein angiography versus ERG for predicting the prognosis in central retinal vein occlusion.

PURPOSE: It is not easy to predict which patients with a central retinal vein occlusion will develop rubeosis and which will not. We have compared two methods for doing so, fluorescein angiography and full-field electroretinogram (ERG). Our aim was to improve our possibilities for predicting rubeosis in patients with central vein occlusion. METHODS: 32 patients with a central retinal vein occlusion with a duration of less than 14 days were included in the study. Fluorescein angiography and ERG were performed in all patients. The fluorescein angiograms were studied by two independent examiners in a masked mode. The patients were then followed for at least one year. RESULTS: Development of rubeosis in patients with central retinal vein occlusion could be predicted by fluorescein angiography in 82% of the patients and with ERG in 94% of the patients. The non-ischemic central retinal vein occlusions were identified in 62% by fluorescein angiography and in 100% with ERG. Fluorescein angiography misjudged 9 patients 28%, whereas ERG only misjudged 1 patient, 3%. CONCLUSION: ERG seems to be a better method for predicting the prognosis in central retinal vein occlusion than fluorescein angiography.

Adult↗

Integrity and metabolism of human ileal mucosa in vitro in the Ussing chamber.

The Ussing chamber is increasingly being used for in vitro studies of human intestinal mucosa, but little attention has been paid to the viability of specimens over time. Ninety-one mucosal specimens from the ileum in 19 patients operated on for colonic cancer were studied in regard to intestinal barrier function, metabolism, electrophysiology and histology during 360 min of incubation in Ussing chambers. Steady-state permeability to 51Cr-EDTA was maintained for 120 min. Mucosal ATP and lactate levels were stable for 180 min and transmucosal glucose flux for 240 min. Lactate dehydrogenase leakage was limited within 120 min. Transepithelial potential difference was 9.0 +/- 3.0 mV at the start, and declined slowly throughout 360 min. Light microscopy revealed epithelial lifting from the basal lamina at 90 min. Transmission electron microscopy demonstrated preserved ultrastructure for 120 min. Specimens with a transepithelial potential difference below 6 mV at the start were associated with increased 51Cr-EDTA permeability and lactate dehydrogenase leakage and more pronounced light microscopy changes. All studied parameters pointed to preserved viability if experiments were kept within a period of 90 min after equilibration. The few specimens with early viability derangement were identified by a transepithelial potential difference below 6 mV at the start. The Ussing chamber provides a tool for in vitro studies of human intestinal epithelium, including permeability. To minimize viability problems, experiments should be limited in time and monitored by measurements of transepithelial potential difference.

Adenosine Triphosphate↗

An increase in mucosal insulin-like growth factor II content in postresectional rat intestine suggests autocrine or paracrine growth stimulation.

BACKGROUND: Luminal nutrients and growth factors regulate postresectional intestinal growth. The interplay between glutamine and regulatory gastrointestinal peptides is not known. METHODS: The effects of intestinal resection on tissue and plasma concentrations of peptides were studied in 60 Sprague-Dawley rats divided into resected, transected, or unoperated groups. Subgroups were fed either a glutamine-free or a glutamine-supplemented diet for 7 days. Epidermal growth factor, transforming growth factor-alpha, insulin-like growth factors (IGF) I and II, peptide YY (PYY), and enteroglucagon were analyzed in intestinal mucosa and in portal plasma by radioimmunoassay. RESULTS: No glutamine-specific effects were seen. The mucosal content of IGF-II (P < 0.01) and the portal levels of enteroglucagon and PYY (P < 0.05-0.01) increased after intestinal resection. CONCLUSIONS: The increase in PYY and enteroglucagon in portal blood supports a hormonal role in the postresectional adaptation. The increase in IGF II in the ileal mucosa, without changes in plasma, implies autocrine or paracrine growth stimulation at this stage after resection.

Adaptation, Physiological↗

Sexual function one year after transurethral prostatic resection. Patients' own assessments.

One year after transurethral resection of the prostate for benign hyperplasia, 127 men received a questionnaire requesting personal evaluation of sexual function, including erection, ejaculation, libido and satisfaction. Significant postoperative dysfunction was reported in all these respects: 54% of the responders claimed deterioration and half of them blamed the operation. Decline in sexual function had a multifactorial background, including advancing age, morbidity, and changed marital and social conditions. Although other examinations with preoperative and postoperative evaluation report a lower incidence of impotence development, which may be more reliable, it is psychologically interresting that the patients themselves suspect the transurethral resection as the cause of impaired sexuality.

Adult↗

Life threatening diarrhoea ultimately cured by surgery.

A 30-year-old previously healthy woman was diagnosed as having a vasoactive intestinal polypeptide (VIP)-producing tumour of the pancreas. Her medical history was typical for neuroendocrine gastrointestinal tumours, presenting initially with non-specific symptoms but eventually she developed life-threatening manifestations requiring intensive care due to severe dehydration. She immediately recovered following surgical resection. The patient had elevated serum concentrations of VIP as well as pancreastatin, and post-operatively elevated concentrations of three growth factors, IGF-I, EGF and TGF-alpha, were seen. The importance of the alterations in plasma concentrations of the different peptides for her symptomatology are discussed.

Adult↗

Ultrasound enhanced thrombolysis in experimental retinal vein occlusion in the rabbit.

AIMS: To investigate if it was possible to lower the dose of streptokinase and maintain an effective thrombolysis by adding pulsed low energy ultrasound. METHODS: 53 retinal veins in 27 rabbits were occluded by rose bengal enhanced laser treatment. Six rabbits were treated with streptokinase (50,000 IU/kg), 10 rabbits were treated with a low dose of streptokinase (25,000 IU/kg), and 11 rabbits were treated with a low dose of streptokinase (25,000 IU/kg) and pulsed ultrasound during 1 hour. Fluorescein angiography was performed immediately before the thrombolytic treatment and after 12 hours. RESULTS: In the group treated with streptokinase (50,000 IU/kg) all vessels were open. In the group that was given streptokinase (25,000 IU/kg), 21% of the vessels were open. In the group that was treated with streptokinase (25,000 IU/kg) and ultrasound, 64% of the vessels were open. The difference between groups 2 and 3 is statistically significant (p = 0.011) CONCLUSION: Adding pulsed low energy ultrasound makes it possible to lower the dose of streptokinase while maintaining a good thrombolytic effect.

Animals↗

Skeletal muscle insulin resistance after trauma: insulin signaling and glucose transport.

Surgical trauma induces peripheral insulin resistance; however, the cellular mechanism has not been fully elucidated. We examined the effects of surgical trauma on insulin receptor signaling and glucose transport in skeletal muscle, a tissue that plays a predominant role in maintaining glucose homeostasis. Surgical trauma was induced by intestinal resection in the rat. Receptor phosphorylation was not altered with surgical trauma. Phosphotyrosine-associated phosphatidylinositol (PI) 3-kinase association was increased by 60 and 82% compared with fasted and fed controls, respectively (P < 0. 05). Similar results were observed for insulin receptor substrate-1-associated PI 3-kinase activity. Insulin-stimulated protein kinase B (Akt kinase) phosphorylation was increased by 2.2-fold after surgical trauma (P < 0.05). The hyperphosphorylation of Akt is likely to reflect amplification of PI 3-kinase after insulin stimulation. Submaximal rates of insulin-stimulated 3-O-methylglucose transport were reduced in trauma vs. fasted rats by 51 and 38% for 100 and 200 microU/ml of insulin, respectively (P < 0.05). In conclusion, insulin resistance in skeletal muscle after surgical trauma is associated with reduced glucose transport but not with impaired insulin signaling to PI 3-kinase or its downstream target, Akt. The surgical trauma model presented in this report provides a useful tool to further elucidate the molecular mechanism(s) underlying the development of insulin resistance after surgical trauma.

Animals↗

Sufficiency of postprandial plasma levels of islet amyloid polypeptide for suppression of feeding in rats.

Our objective was to study whether islet amyloid polypeptide (IAPP) produces satiety by an endocrine mechanism. We used a rat model to determine whether postprandial plasma levels of IAPP are comparable to those required to inhibit feeding when IAPP is administered by continuous intravenous infusion. Food intake in rats with aortic catheters increased plasma IAPP levels from a fasting level of 10.8 +/- 0.5 pM to a peak level of 19.0 +/- 1.0 pM at 2.2 +/- 0.5 h. In rats with jugular vein and aortic catheters, the threshold intravenous dose for IAPP suppression of feeding was between 1 and 3 pmol . kg-1 . min-1. The 3 pmol . kg-1 . min-1 dose decreased 4-h intake by approximately 25% by decreasing meal frequency rather than meal size. This dose increased plasma IAPP by approximately 24 pM. These results suggest that postprandial plasma levels of IAPP are not quite sufficient to independently produce satiety.

Amyloid↗

Long-term prognosis after healed amputation in patients with diabetes.

In this prospective study, mortality, rehabilitation, and new amputations on the same or on the contralateral leg were studied in 189 patients with diabetes who had achieved healing of an index amputation. Ninety-three patients had achieved healing after an index minor (below the ankle) and 96 after an index major (above the ankle) amputation, precipitated by a foot ulcer. The healing time was 29 weeks (range, 3-191 weeks) with a minor amputation and 8 weeks (range, 3-104 weeks) with a primary major amputation. The mortality 1, 3, and 5 years after the index amputation was 15%, 38%, and 68%, respectively, and was higher in patients who had achieved healing after major amputation than in patients achieving healing after minor amputation. The rate of new amputations after 1, 3, and 5 years of observation was 14%, 30%, and 49%, respectively. There was no difference among patients with an index minor and those with an index major amputation. The rate of new major amputations was 9%, 13%, and 23%, respectively, and was higher in patients with an index major amputation. Eighty-five percent of new amputations were precipitated by a foot ulcer. Patients living independently before the index amputation returned to living independently more often after a minor than a major amputation (93% versus 61%). One year after the index amputation, 70% of patients who had achieved healing after having a minor amputation and who could walk 1 km or more before amputation had regained this walking capacity, compared with 19% of patients having a major amputation. Seventy percent of patients with an index transtibial amputation who could walk before amputation were fitted with a prosthesis, and 52% were using it regularly. Patients with diabetes who had an index major amputation had a higher mortality, an equal rate of new amputation, and a lower rehabilitation potential than did patients who had an index minor amputation.

Adult↗

Dissociated secretion of islet amyloid polypeptide and insulin in serum-free culture media conditioned by human pancreatic adenocarcinoma cell lines.

CONCLUSION: The cosecretion of insulin and islet amyloid polypeptide (IAPP) is altered when isolated rat pancreatic islets are incubated in culture media conditioned by human pancreatic cancer cells. BACKGROUND: Pancreatic cancer is usually associated with impaired glucose tolerance. This study investigates the tumor-derived influence on beta-cell secretion of pancreatic islets. METHODS: Four conditioned media were prepared from two human pancreatic cancer cell lines (Panc-1 and HPAF), a hamster pancreatic cancer cell line (PC-1), and a fibroblast cell line (Ag1523). Isolated rat pancreatic islets were incubated first in the conditioned media or nonconditioned control medium for 24 h, then in the same kind of media containing 100 microM carbamylcholine for 90 min. Insulin and IAPP secretion were measured by radioimmunoassay. RESULTS: Islets in media conditioned by Panc-1 and HPAF cells demonstrated dissociation of insulin and IAPP secretion. During 24-h incubation, the dissociation was expressed as selectively decreased insulin secretion. With addition of 100 microM carbamylcholine, the dissociation was expressed as normal secretion of insulin and hypersecretion of IAPP. As a result, the IAPP/insulin molar ratios were increased in both groups during both time periods. The islets in PC-1 and Ag1523 media did not show any significant changes in insulin and IAPP secretion.

Adenocarcinoma↗

Effects of environmental stress on tissue survival and neutrophil recruitment in surgical skin flaps in relation to plasma corticosterone levels in the rat.

OBJECTIVE: Because glucocorticoid treatment can improve the survival of surgical skin flaps, we examined the influence of environmental stress on skin flap survival in the rat. MATERIAL: Female Sprague-Dawley rats. TREATMENT: Dexamethasone (1 mg/kg i.p.). METHODS: A standardized dorsal skin flap was raised and sutured back into position, and six days latter the percentage of flap survival was assessed. Corticosterone in rat plasma was measured using radioimmuno assay, and skin flap myeloperoxidase accumulation (reflecting neutrophil recruitment) was determined spectrophotometrically. RESULTS: Skin flap survival decreased gradually during a 10 day acclimatization period after transportation of the animals from the supplier, and plasma corticosterone levels were increased during the first 5 days of acclimatization compared to day 7 and 10. Dexamethasone treatment of rats accustomed to their new environment for 10 days increased flap survival to a level close to that observed in animals operated at day 1 after arrival. Flap surgery induced pronounced neutrophil recruitment into flap tissue, and this cell accumulation was greatly reduced in both the dexamethasone treated rats and in rats with elevated corticosterone levels. CONCLUSIONS: Skin flap survival in rats exposed to environmental stress may be significantly increased as compared to animals accustomed to their new environment for one week, possibly as a consequence of anti-inflammatory actions exerted by stress-induced elevations in plasma corticosterone. These findings emphasize the importance of strictly controlling environmental stress factors in studies of inflammation and tissue damage after surgical skin trauma.

Animals↗

Improved wound healing in transtibial amputees receiving supplementary nutrition.

The objective of this prospective study of matched controls was to find out whether supplementary nutrition would improve wound healing and decrease mortality in patients undergoing transtibial amputation for occlusive arterial disease. The nutritional status of 32 consecutive transtibial amputees was assessed and 28 were classified as malnourished. Supplementary nutrition was given reaching an average intake of 2098 kcal/day for a total of 11 days. In 24 patients, at least 5 days of preoperative supplementary nutrition were given, followed by postoperative treatment for a total of 11 days. Four patients who had an immediate operation were given only postoperative treatment, and 4 were excluded. The controls were 32 amputees in another hospital and matching procedures were carried out with corrections for diabetes, sex, age, smoking habits, previous vascular surgery and living conditions before amputation. Healing, including those healed before death in both groups, occurred in 26 of the nutrition group compared to 13 in the control group, which was statistically significant. Nine patients died within 6 months in the nutrition group compared to 14 of the controls (not significant). Malnutrition was present in nearly 90% of transtibial amputees and supplementary nutrition improved healing, but not mortality.

Aged↗

Cloning, mapping and mutational analysis of the S-adenosylmethionine decarboxylase gene in Drosophila melanogaster.

S-adenosylmethionine decarboxylase is a key enzyme in the synthesis of polyamines. These small cationic molecules are required for growth and development in all organisms. A wealth of biological processes, including synthesis of DNA and protein and condensation of chromatin, involve polyamines. Inhibition of polyamine synthesis has been proposed for treatment of cancer but this requires more knowledge about the in vivo function of polyamines. We report here the cloning of the S-adenosylmethionine decarboxylase gene from Drosophila melanogaster and the analysis of corresponding mutants. The mutant phenotypes are similar to those previously described for ribosomal protein genes (Minutes) and rRNA genes (bobbed). This work elucidates the in vivo consequences of impaired polyamine synthesis with respect to the development of a whole animal.

Adenosylmethionine Decarboxylase↗

Islet hormone secretion in pancreatic cancer patients with diabetes.

The diabetes or impaired glucose tolerance that occurs in most patients with pancreatic cancer is characterized by profound insulin resistance. Recent evidence suggests that the diabetes may result from the presence of the tumor rather than being a predisposing factor to development of the malignancy. Some islet hormones have been shown to exhibit diabetogenic effects. To investigate the potential role of these hormones in the diabetic state associated with pancreatic cancer, we measured islet hormones during fasting in pancreatic cancer patients (n = 30), patients with other malignancies (n = 43), and healthy controls (n = 25). Preoperative pancreatic cancer patients were classified as normal glucose tolerance (NGTT), impaired glucose tolerance (IGTT), non-insulin-requiring diabetes (NIRD), and insulin-requiring diabetes (IRD). Nine pancreatic cancer patients were studied after tumor removal by subtotal pancreatectomy. Some preoperative pancreatic cancer patients (n = 19), postoperative patients (n = 9), and controls (n = 8) were also studied during hyperglycemia and following glucagon injection. Fasting plasma C-peptide was elevated in NIRD pancreatic cancer patients compared to controls. Fasting levels of islet amyloid polypeptide (IAPP), glucagon, and somatostatin were elevated in NIRD and IRD patients. IAPP and glucagon, but not somatostatin, normalized following subtotal pancreatectomy. During hyperglycemia, increases in C-peptide and IAPP were seen only in controls and in NGTT and postoperative pancreatic cancer patients. After glucagon infusion, IAPP levels increased in controls and nondiabetic cancer patients; C-peptide levels increased in controls, nondiabetic patients, and NIRD. Responses of C-peptide and IAPP to glucagon normalized after pancreatectomy. During hyperglycemia, glucagon levels fell in all groups except IGTT patients and a decrease in somatostatin concentrations was seen in controls.

Adenocarcinoma↗

Activated protein C resistance in patients with central retinal vein occlusion.

AIM/BACKGROUND: A new defect in the anticoagulant system has recently been discovered--activated protein C resistance. The frequency of this disorder has been shown to be increased in young patients (< 50 years of age) with central retinal vein occlusion. This study was carried out to determine if there was any overrepresentation of activated protein C resistance in patients > 50 years of age with central retinal vein occlusion. METHODS: Blood samples were obtained from 83 patients > 50 years of age and with a history of central retinal vein occlusion. The blood samples were analysed for activated protein C resistance with standard clinical laboratory methods. RESULTS: In this material 11% of the patients were resistant to activated protein C. The normal incidence of activated protein C resistance in the same geographical area is 10-11%. CONCLUSION: Activated protein C resistance does not seem to be a cause of central retinal vein occlusion in people older than 50 years.

Aged↗

Trophic effects by epidermal growth factor on duodenal mucosa and exocrine pancreas in rats.

Epidermal growth factor (EGF) is a potent growth factor with possible implications on the regulation of pancreatic secretion and duodenal absorption but also on pancreatic tumor growth. In the present study the growth effect on duodenal mucosa and pancreas by a 14-day continuous infusion of three different doses of EGF (4, 30 and 60 micrograms EGF/kg/24 h) was studied in rats. The EGF content in duodenal mucosa and pancreatic tissue was significantly increased by 30 and 60 micrograms/kg/24 h of EGF while plasma levels were only marginally increased. Neither duodenal mucosal nor pancreatic weights were changed but DNA content in both tissues was increased with the higher EGF doses. Long-term EGF infusion has moderate trophic effect on duodenal mucosa and the pancreas. There is a high tissue uptake of EGF, specially in duodenal mucosa. The hyperplasia seems to be related to tissue levels of EGF but not to plasma levels.

Animals↗