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Biomedical subjects

K Fält

Publications and source records attributed to K Fält.

At least 19 recordsLinked to original sources
PubMed1996

Recovery of endothelial cells and prostanoid production in endothelial cell-seeded grafts.

OBJECTIVE: To investigate the function and morphology of endothelial cell (EC) seeded grafts. DESIGN: Experimental, open study. CHIEF OUTCOME MEASURES: Endoluminal release of prostacyclin (6-Keto-PGF1 alpha) and thromboxane B2 (TxB2), patency, EC coverage and cell identity. MATERIALS: In 12 sheep, segments of both carotid arteries were excised. On one side a seeded and on the other an unseeded dacron graft were inserted. After 3 months the grafts were excised. In grafts and arteries, the endoluminal release of 6-keto-PGF1 alpha and TxB2 was determined in a perfusion system. Scanning electron microscopy (SEM) and light microscopy were used to determine the EC coverage and cell identity. RESULTS: Eight animals survived. Three seeded and two unseeded grafts were occluded. Prostacyclin release did not differ significantly between seeded and unseeded grafts and arteries, when the arteries were looked upon as one group. When the graft was compared with its corresponding artery, i.e. the artery it replaced, a significantly lower release was found in the unseeded group. Thromboxane release was undetectable in arteries but significantly higher in both graft groups. SEM revealed a cellular coverage of 75% in the seeded grafts and 50% in the unseeded (not significant). Light microscopy showed a patchy staining for Factor VIII-related antigen in some grafts in both groups. CONCLUSION: Prostacyclin release in unseeded and seeded dacron grafts did not differ 3 months after implantation in sheep, except when the graft was compared with its corresponding artery. The significance of this remains to be settled. Seeded grafts did not have a higher proportion of endothelial coverage than unseeded grafts.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus.

The mechanisms by which the beta cells of pancreatic islets are destroyed in insulin-dependent diabetes mellitus (IDDM) are poorly understood. In this report the pancreatic histo- and immunopathology of two children, both HLA-DR 3/4, DQ 2/8 positive and who both died from cerebral oedema within a day of clinical diagnosis of IDDM, were investigated. Patient 1, a 14-month-old girl, had a 4-week history of polydipsia and polyuria. Patient 2, a 3-year-old boy, had 2 days of illness. Both patients had a similarly severe loss of insulin cells but differed markedly as to the extent of lymphocytic islet infiltration (insulitis). Apart from insulitis, marked islet macrophage infiltration was demonstrated in both patients with the HAM-56 monoclonal antibody. Neither patient showed aberrant expression of HLA class II antigens on insulin-immunoreactive cells, but allele-specific HLA-DQ8 expression was evident on endothelial cells. Glutamic acid decarboxylase immunoreactivity was detected in both insulin- and glucagon-immunoreactive cells. It is concluded that the heterogeneity of islet pathology, especially insulitis, may reflect different dynamics and extent rather than different pathomechanisms of immune destruction of islets in IDDM.

Child, Preschool↗
PubMed1994

Calcitonin gene-related peptide attenuates experimental ischemic renal failure in a rat model of reversible renal ischemic insult.

Calcitonin gene-related peptide (CGRP) has been shown to decrease vascular resistance and increase renal blood flow. To study the effects of CGRP in acute renal failure (ARF) of moderate degree, we used a rat model of bilateral temporary renal artery occlusion (RAO) inducing ARF with spontaneous recovery within 1 week, resembling a clinical situation. Three groups were studied: CGRP 10 (CGRP10) and 25 (CGRP25) pmol.kg-1.min-1 and vehicle alone (control), respectively, infused from 10 min before until 2 h after declamping. Serum urea levels reached a peak after 24 h at 13.0 +/- 1.3, 8.1 +/- 1.1, and 8.5 +/- 1.0 mmol.L-1 in the control, CGRP10, and CGRP25 group, respectively. They were significantly lower postischemia in the two CGRP-treated groups than in the control group. Mean arterial pressure (MAP) decreased to 90%, 80%, and 60% of baseline MAP in the control, CGRP10, and CGRP25 group, respectively. Histologically there was no significant difference between the three groups. Our data indicate that CGRP preserves renal function in experimental ARF despite reductions in MAP. We conclude that further investigations of the renal effects of CGRP are needed in order to clarify whether CGRP might be used clinically to maintain or improve renal function in ARF.

Acute Kidney Injury↗
PubMed1994

Renal arteriovenous shunting in rejecting allograft, hydronephrosis, or haemorrhagic hypotension in the rat.

We studied the occurrence of arteriovenous (A-V) shunting in three experimental rat models, namely in rejecting allograft kidney, in uni- or bilateral ureteral obstruction, and in haemorrhagic hypotension. Isografted or sham-operated rats served as controls. Radiolabelled microspheres were injected into the renal artery and the increase in the amount of radioactivity in the lungs was considered to reflect A-V shunting in the kidney. In animals exposed to haemorrhage, with a blood pressure not less than 70% of the initial blood pressure, practically no shunting was seen. When animals were bled to a hypotension beyond the autoregulation, A-V shunting occurred inversely correlated to the degree of hypotension. In ureteral obstruction, a less marked but significant increase in shunting of microspheres to the lungs was found after 24 h of unilateral obstruction, irrespective of whether the spheres were injected into the obstructed or the contralateral kidney. Significant A-V shunting during the allograft rejection process was also demonstrated. Histologically, microspheres were found in afferent arterioles less frequently in kidneys with A-V shunting than in controls. These results indicate that A-V shunting is involved in haemorrhagic hypotension, renal graft rejection, and hydronephrosis. In the latter situation A-V shunting is probably regulated by a humoral factor.

Animals↗
PubMed1993

Reperfusion of duodenum and pancreas following 24 hr of cold storage in Perfadex or UW solution.

We have studied the immediate reperfusion and the graft outcome of the duodenum and pancreas separately in a porcine whole-organ pancreaticoduodenal allograft transplantation model using 24 hr of cold storage. Of 19 transplantations, 12 grafts were perfused and stored in Perfadex and 7 in University of Wisconsin (UW) solution. The organ weights before and after storage were determined in 6 grafts stored in Perfadex and 6 grafts stored in UW solution in order to quantify the degree of dehydration of the graft during storage. In 6 of the grafts perfused with Perfadex, a hyperosmotic salt dextran-containing solution (HSD) was perfused into the graft aorta at reperfusion. Duodenal reperfusion and reperfusion injury were studied by measuring mucosal pH (pHi) and by microscopic examination, respectively. Pancreatic reperfusion was studied by scoring the macroscopic appearance and microscopic examination. Daily blood glucose was used to determine the endocrine function and a secretin-cholecystokinin stimulation test was performed on the second postoperative day to evaluate the exocrine function. All duodenal grafts except 1 in the UW group showed a sufficient reperfusion according to pHi and all had microscopic changes suggesting a moderate reperfusion injury. The macroscopic appearance of pancreas was significantly worse in the UW group than in the two Perfadex groups. Only 1 of 7 grafts in the UW group showed signs of endocrine function on the first postoperative day compared with 11 of 12 in the Perfadex groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1993

A comparison between IEEC, a new biodegradable particulate contrast medium, and iohexol in a tumor model of computed tomography imaging of the liver.

RATIONALE AND OBJECTIVES: Higher contrast between normal and pathologic tissues in the liver may enable detection of smaller lesions in computed tomography (CT). This can be obtained using a liver-specific contrast medium. The authors evaluate a new agent, IEEC (1'-Ethyloxycarbonyloxy)-ethyl-5-acetylamino-3-(N-methyl-acetylami no)-2,4,6- triiodo-benzenecarboxylate), in an animal model, as a potential contrast agent for CT scanning of the liver. The IEEC particulate contrast medium used is based on a prodrug ester design of metrizoic acid and accumulates rapidly in the liver. The particles are quickly degraded into well-known metabolites and excreted from the body. METHODS: Two groups of rabbits were inoculated with VX2-carcinoma directly into the liver by laparotomy. Computed tomography imaging studies were carried out 9 and 11 days after the inoculation. The investigation was designed as a crossover study. The first group was imaged both as controls (without contrast medium) and with the particulate contrast medium on the 9th day and with iohexol on the 11th day. The second group was imaged with iohexol on the 9th day and as controls, and with the particulate contrast medium on the 11th day. The contrast medium was administered in a dose of 100 mgI/kg. Iohexol was administered in a dose of 570 mgI/kg according to a standard clinical scheme in use at a radiology department for dynamic CT. Changes in normal liver/lesion contrast and the conspicuity of tumors were assessed. On completion of imaging studies on day 11, all animals were killed. The liver was removed and evaluated for the presence of tumors. RESULTS: At macroscopic inspection, all rabbits were found to have tumors ranging from 2 to 14 mm in diameter. The size and location of the tumors corresponded well with the CT images. In the images where the particulate contrast medium was used, the attenuation in the normal liver parenchyma and the contrast between normal liver and lesion was significantly higher compared with the images where iohexol was used or the controls. For all tumor sizes, the lesion detection capability with the particulate contrast medium was significantly higher compared with iohexol (P < .005) and controls (P < .05). CONCLUSIONS: VX2-carcinoma in rabbit liver is a useful model for studying the efficacy of contrast media in CT imaging. The particulate contrast medium IEEC improved visualization of liver tumors.

Animals↗
PubMed1993

Prostanoid release immediately after balloon angioplasty in three models of atherosclerosis in rabbits.

OBJECTIVE: To evaluate the effect of angioplasty on the production of prostanoids in atherosclerotic vessels in rabbits. DESIGN: Open study. MATERIAL: 38 Rabbits. INTERVENTIONS: Rabbits in group A (n = 12) were given a cholesterol rich diet (2%) for 10 weeks, and then treated with angioplasty. Rabbits in group B (n = 11) were given a cholesterol rich diet for 10 weeks, and then returned to a normal diet until the serum cholesterol concentration returned to the reference range (a further 12 weeks). Rabbits in group C (n = 15) were anaesthetised, and a 3 mm balloon was introduced into the right femoral artery, fed 20 cm proximally, inflated, and pulled twice along the aorta; the animals were then given a cholesterol rich diet (2%) for eight weeks, and treated with angioplasty. MAIN OUTCOME MEASURES: Serum cholesterol concentrations were measured once a week. Prostacyclin and thromboxane were measured as 6-keto prostaglandin F1 alpha and thromboxane B2 in both treated and control segments of aorta. RESULTS: 15 Rabbits died while atherosclerosis was being induced, leaving 23 for analysis. Angioplasty reduced the amounts of prostanoids released in animals in which the atherosclerosis had been induced by diet alone. When endothelial injury and diet were used together, there was no difference between the treated and control segments in the amounts of prostanoids released. CONCLUSION: These findings could be of use in the comparison of methods used to induce atherosclerosis, and in the study of the mechanisms of thrombosis after transluminal angioplasty.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Beta-endorphin-immunoreactive cells in the human fetal pancreas.

This investigation has been carried out on 50 samples of fetal pancreata from the 10th to the 32nd week of gestation using the PAP technique. beta-Endorphin-reactive cells were morphometrically recorded by means of the point-counting method. beta-Endorphin reactivity occurred for the first time during the 15th week. During further development, beta-endorphin cells were found inside and outside the islets. From the 18th to 23rd week, these cells were primarily localized in the islet periphery. From the 24th week, they rearranged and occurred in irregular positions mixed with other islet cells. This rearrangement took place with a 4 week delay compared with the basic cell types of the islet organ. The extrainsular portion of these cells in the exocrine parenchyma varied between 0.3% in the 27th week and up to 10% in the 22nd week. Concerning the adult human pancreas, it has been suggested whether beta-endorphin cells may be a 6th basic cell type of the islet organ. Previous studies on the coexistence of somatostatin, glucagon and beta-endorphin in the same islet cell and the morphometric analysis would support this assumption. Biochemical examinations indicate that beta-endorphin is a modulator of insulin, glucagon, and somatostatin secretion in the islet organ. This is supported by the fact that beta-endorphin cells have extended cell bodies which is typical of cells with paracrine function.

Cell Count↗
PubMed1992

Prostacyclin is produced from endothelial cell-seeded grafts: an experimental study in sheep.

Endothelial cell seeding might be of value in reducing the thrombogenicity of small-diameter vascular grafts. We investigated the capacity of endothelial cell-seeded grafts to produce prostacyclin and compared this with that of the unseeded graft as well as the native artery. Twelve sheep were operated on with carotid interposition of externally supported knitted dacron grafts. On one side of the neck the graft was seeded with endothelial cells, enzymatically harvested from the left jugular vein. After 3 weeks, three out of 12 seeded grafts, and one out of 12 unseeded grafts were occluded (N.S.). After excision, the grafts were mounted and perfused ex vivo for five 15-min periods. During the last period, arachidonic acid (4 micrograms/ml) was added to the perfusate. The resected carotid artery was used as a control. Prostacyclin was determined as the stable degradation product 6-keto-PGF1 alpha using radio-immunoassay, and expressed as pg mm-2 luminal surface. The native artery had a significantly higher release of prostacyclin than the seeded graft, which in turn had a significantly higher release than the unseeded graft. Histological examination showed weakly positive staining for factor VIII-related antigen on the luminal surface of seeded grafts. Scanning electron microscopy showed endothelial cells with typical endothelial tufts and was evaluated blindly from 10 areas of each graft. The extent of endothelial cell coverage was evaluated and scored from 0 to 2.5. The median score for the unseeded grafts was 0.3 and for the seeded grafts 1.5 (p = 0.008). Prostacyclin production was higher in seeded than unseeded grafts, but did not influence patency in this model.

Animals↗
PubMed1992

Vessel repair after balloon angioplasty: morphological appearance and prostacyclin synthesising capacity.

Immediately after balloon dilatation of the rabbit aorta the release of prostacyclin is diminished. In this study the morphological appearance and time course for recovery of prostacyclin production after balloon dilatation have been investigated. Healthy rabbit aortas were analysed 1 h (n = 12), 1 week (n = 13) and 1 month (n = 13) after angioplasty. The production of prostacyclin, from dilated and non-dilated aortic segments, was recorded in a perfusion system. Prostacyclin was measured as its stable degradation product 6-keto-PGF1 alpha. Scanning electron microscopy and light microscopy were used to analyse the type of cells present at the luminal surfaces of the segments. When endothelial cells were found their degree of coverage was also estimated. One hour after balloon dilatation there was a lower production of prostacyclin from the angioplasty segments than from controls. Also, the response to added arachidonic acid (AA) was lower in the angioplasty segments. No endothelial cells were present in the angioplasty segments. After 1 week there was no difference in the basic production of prostacyclin but there was still a lower response from angioplasty segments to the addition of AA. The inner surfaces of the angioplasty segments were covered by three to five layers of smooth muscle cells (SMC). After 1 month, there was no difference in either the basic production or after the addition of AA between control and angioplasty segments. The angioplasty segments were covered with a multilayer of SMC. The control segments had an almost complete cover of endothelial cells at every time interval after angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1991

Islet cell antibody reactivity with human fetal pancreatic islets.

To evaluate the possibility of autoimmune processes against pancreatic islets in fetal life, we tested islet cell antibody (ICA) reactivity with 14 fetal pancreata obtained after abortion at the 15th up to the 19th week of gestation. Pancreatic islets positive for a monoclonal proinsulin antibody but non-reactive with ICA negative control serum were found in 9/14 pancreata and all (9/9) of them showed a positive reaction with the ICA standard. It is concluded that ICA reactivity may be detected in fetal human pancreata. Further studies on fetal islet cell antibody reactivity in the development of insulin dependent diabetes mellitus (IDDM) are warranted.

Autoantibodies↗
PubMed1991

Detection of proinsulin, C-peptide, insulin-A-chain, and glicentin in pancreatic islet cells of early human fetogenesis.

The presence of C-peptide, proinsulin, insulin-A-chain, and glicentin in human fetal pancreatic cells by using the PAP-technique was investigated and the results obtained compared with the occurrence of insulin or glucagon immunoreactive cells. In pancreatic sections obtained from 10 weeks old human fetuses we could identify cells reacting with antibodies directed against C-peptide, proinsulin, and insulin-A-chain. The majority of the cells were found in the duct epithelium and their number increased from the 10th to 14th week forming clusters near the ducts. The number and localization of the cells correspond exactly to the insulin positive cells. The presence of proinsulin and insulin-A-chains is a further proof of biological activity already in an early step of fetal development. The presence of glicentin-positive cells in the 10th week of gestational age as well as cells reacting with glucagon antibodies provide evidence for active glucagon biosynthesis. The number of these cells increased markedly in the 14th week of gestational age.

Antibodies↗
PubMed1991

Early indicators of allograft rejection in a porcine pancreatic transplantation model.

Urine cytology and blood lymphocyte blastogenesis were evaluated as indicators of allograft rejection in a porcine pancreatic transplantation model. The percentage of activated lymphocytes and/or blasts was significantly increased during the rejection phase. Positive cytology was present in all rejection episodes. An increased thymidine uptake of blood lymphocytes and a decreased uridine/thymidine uptake quotient were seen prior to the onset of rejection. The reported dissociation of anionic and cationic trypsin levels in serum and urine after transplantation was not seen after simple urinary diversion of the pancreatic juice. This supports the hypothesis that a decreased synthesis of cationic trypsinogen compared with anionic trypsinogen occurs after porcine pancreatic transplantation.

Animals↗
PubMed1990

Development of cytotoxic islet cell antibodies in rats following damage of the pancreas by complete Freund's adjuvant combined with a nondiabetogenic dose of streptozotocin.

The possible relationship between destruction of pancreatic beta cells and islet cell surface antibodies (ICSA) was examined in a rat model using complete Freund's adjuvant (CFA), a lymphocyte activator, in combination with the beta cell toxin, streptozotocin (STZ). In addition to this treatment, the rat insulinoma cell line, RIN5AH, as a readily accessible source of insulin-producing cells, was utilized to potentiate the production of ICSA. Intraperitoneal injections of CFA to male Lewis rats, followed 24 h later by a single nondiabetogenic dose of STZ, produced a 47% (p less than 0.01) reduction in pancreatic insulin content associated with degranulation and necrosis of insulin-immunoreactive cells. Eight weeks after treatment, ICSA were detectable that mediated the complement-dependent lysis of neonatal rat islet cells. Injections of RIN5AH cells, following treatment with CFA/STZ, did neither increase the severity of histopathological changes in the exocrine pancreas nor the extent of beta cell necrosis, but gave rise to higher levels of cytotoxic ICSA. Immunization with RIN cells alone, although increasing ICSA levels above those of the other experimental groups, produced no major histopathological changes. These results indicate that ICSA are the consequence of beta cell damage, and they are not capable of promoting or initiating beta cell necrosis in this model.

Animals↗
PubMed1990

Argyrophil and beta-endorphin immunoreactive cells in focal islet-cell adenomatosis and insulin-producing islet-cell adenomata.

Pancreatic tissue from 3 cases of hyperinsulinemic hypoglycemia was examined using histochemical and immunoperoxidase staining techniques. The insular lesions present were adenomatosis and insulin-producing islet-cell adenomata. The great majority of the islet parenchymal cells in these lesions were reactive with antibodies to pro-insulin, C-peptide, and insulin. A variable number of islet cells was found to react with beta-endorphin antiserum in all 3 cases, while the reaction with antiserum against the neural tissue marker antigen, S-100, was restricted to the cases with islet-cell adenoma. Argyrophil parenchymal cells were present in focal adenomatosis but almost absent in insulomata. These results suggest that various lesions of the endocrine pancreas causing hypoglycemia can be distinguished by means of specific histo- and immunocytochemical methods because of differences in the distribution of characteristic cellular antigens.

Adenoma↗
PubMed1990

Histopathological lesions in the pancreas of a rat model of diabetes induced with complete Freund's adjuvant and low-dose streptozotocin.

Neither injection of complete Freund's adjuvant (CFA) alone nor the administration of low doses of streptozotocin (STZ) to rats produced remarkable histopathological changes in the endocrine pancreas, but treatment with the combination of both resulted in necrosis of beta cells. When the combination of CFA/STZ was given two times, necrosis progressed, and the beta cell reserve was depleted to such an extend that persistent hyperglycemia ensued. These changes were associated with a significant reduction in the apparent islet size. A single injection of CFA induced pancreatitis and inflammatory lesions in the exocrine parenchyma with no insular involvement. Three injections caused extensive destruction of pancreatic acinar tissue but only moderate beta cell injury in the minority of islets. Apart from mild degranulation of beta cells, treatment with STZ did not produce histopathological changes in the pancreas. These results suggest that the acute inflammatory process induced by CFA may initially damage the beta cells, increasing thereby their susceptibility to the action of STZ.

Animals↗
PubMed1990

[Origin of islets of Langerhans by mitotic division of duct epithelium in the human early fetal period].

The investigations are carried out in 29 human fetal pancreases between the 10th and 19th week of age. Mitosis restricted to the duct epithelium in the 10th to 13th week. In the 14th week start the mitotic activity in the islet parenchyma. The mitotic activity decreased from the 10th to the 13th week, increased to the 15th week and decreased once more to the 19th week.

Cell Division↗