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Biomedical subjects

K Fält

Publications and source records attributed to K Fält.

At least 55 records · Page 3Linked to original sources
PubMed1987

Biochemical, immunohistochemical and ultrastructural studies of the alteration of pancreatic beta cells resulting from the combined effects of complete Freund's adjuvant and non-diabetogenic doses of streptozotocin.

Injection of complete Freund's adjuvant (CFA) 24 h prior to treatment of rats with non-diabetogenic doses of streptozotocin (STZ) produced a reduction in pancreatic insulin content associated with ultrastructural changes and a decrease of the volume density of insulin-immunoreactive cells without affecting other islet cells. After one injection of CFA and STZ, pancreatic insulin content was decreased by 69% (p less than 0.01) within 48-96 h, while plasma glucose concentrations were not changed. The volume density of beta cells in pancreata of these rats was reduced by 40% (p less than 0.01) compared with citrate-saline treated control rats. No significant lymphocytic infiltration was detectable in islets, but the exocrine pancreas exhibited inflammatory lesions. Degranulation and vacuolation was evident by ultrastructural analysis. Following administration of CFA or STZ alone, pancreatic insulin content was insignificantly reduced, and major histopathological changes in pancreatic islets were apparently absent. These results support the hypothesis that activation of the immune system by CFA allows an anti-beta cell reaction to develop following exposure to the beta cell toxic agent STZ.

Animals↗
PubMed1987

Secretory state and acute gastric mucosal injury in sepsis.

Cats were subjected to a standardized 3-h septicemia by intravenous infusion of live Escherichia coli in an LD50 dose. The effect of pentagastrin stimulation on the development of gastric mucosal injury was studied. There was no hemodynamic difference between the series during septicemia. Thus, pentagastrin did not induce increased gastric blood flow during the period of E. coli infusion. Intraluminal gastric pH was lower in the series given pentagastrin during the last 2 h of septicemia. Nevertheless, the extent of gastric mucosal injury was similar in the two groups, whereas the depth of injury was, if anything, less pronounced in the pentagastrin-stimulated group.

Acute Disease↗
PubMed1987

Ontogeny of the pancreatic islet parenchymal cells in the rabbit--an immunohistochemical and ultrastructural study with particular regard to the earliest appearance of argyrophil insulin-immunoreactive cells.

Six early developmental stages of the rabbit pancreas were selected, viz. the embryonic ages 10 days 10 hours, 10 days 18 hours, 11 days 14 hours, 13 days, 15 days, and 18 days. Both non-immunological (histologic-tinctorial features, including argyrophilia, and transmission electron microscopy) and immunohistochemical (the indirect immunofluorescence and/or the peroxidase-anti-peroxidase procedure) methods were used to follow the time-course for the appearance and differentiation of both endocrine (islet) cells and exocrine acinar epithelium. The immunological procedures were, however, limited to the 3 later developmental stages. In the first 3 developmental stages only the dorsal anlage of the pancreas could be found. It was just investigated ultrastructurally. Then, a few parenchymal cells were observed, equipped with secretory granules of endocrine type, indicating that an early differentiation of islet cells had already begun. In the later 3 developmental stages a ventral pancreas anlage was present and at least 2 types of argyrophil islet cells, equipped with secretory granules, were observed. In the pancreas anlage of 13-day-old embryos these early endocrine cells were found to be glucagon-immunoreactive. At the developmental age of 15 days argyrophil insulin-immunoreactive cells were also present, and in the 18-day-old embryos a few somatostatin cells could occasionally be discovered, too. No PP cells were found. Any exocrine acinar differentiation (with zymogen granules) was not observed until at the developmental age of 18 days.

Aging↗
PubMed1987

Tissue cultivation as a method for preservation of human foetal islet parenchyma--a correlated biochemical, immunohistochemical and morphometric investigation.

Tissue culture of human foetal pancreas slices, obtained at a gestational age between 10 and 19 weeks, as a method of preservation and to pool the material before transplantation was investigated. Before and after 2 weeks of culture the pancreatic insulin content, the insulin secretion in response to glucose and isobutylmethylxanthin (IBMX) as well as the protein biosynthesis were measured. In addition, the distribution of the insulin immunoreactive cells was examined, as well as their relative volume density. After 2 weeks' culture an increase of the basal insulin secretion was observed; this was probably due to the glucose content (10 mmol/l) in the culture medium. Neither the stimulated insulin secretion, nor the protein biosynthesis, the insulin content, and the B-cell volume were altered by the used culture conditions. It was concluded that tissue culture is a suitable method to preserve human foetal pancreas slices before transplantation.

Culture Techniques↗
PubMed1987

Destruction of pancreatic beta cells in rats by complete Freund's adjuvant combined with non-diabetogenic doses of streptozotocin.

Non-specific activation of the immune system by complete Freund's adjuvant (CFA) in combination with non-diabetogenic doses of streptozotocin (STZ) was used to study autoimmune reactions against pancreatic islets. Male Lewis RT1a rats received either CFA (0.5 ml/kg) 24 hr prior to the injection of STZ (25 mg/kg), or CFA or STZ alone. The injections of CFA followed by STZ, but not CFA or STZ alone, produced a 69% (p less than 0.01) reduction in pancreatic insulin content associated with necrosis and a decrease of the relative volume density of insulin-immunoreactive cells without affecting other islet cells. Two injections of CFA and STZ induced hyperglycemia. This was associated with a depletion of pancreatic insulin and a significant reduction in the relative volume density of insulin-immunoreactive cells (p less than 0.01) and in the mean islet area (p less than 0.01). On day 20, after treatment with 3 injections of CFA and STZ, the animals developed persistent hyperglycemia. The pancreata in these rats contained less than 12% B-cells, and the insulin content was reduced by 96% (p less than 0.01). The main components of the remaining atrophic islets were glucagon- and somatostatin-immunoreactive cells. No significant lymphocytic infiltration into the islets was detectable, but the exocrine parenchyma exhibited severe inflammatory lesions. Degranulation and vacuolation of B-cells was evident by ultra-structural analysis. The volume densities of insulin containing cells and islet area were not changed after 3 injections of either CFA or STZ alone, although the pancreatic insulin content decreased by 61% (p less than 0.01) and 39% (p less than 0.05), respectively. These treatments did not produce an increase in plasma glucose. The present results demonstrate that CFA in combination with non-diabetogenic doses of the beta cytotoxic agent STZ induces B-cell destruction without significant insulitis. Our observations support the hypothesis that activation of the immune system by CFA allows an anti-B-cell immune reaction to develop following exposure to STZ.

Animals↗
PubMed1985

Gastric mucosal damage in sepsis--effects of pretreatment with a synthetic prostaglandin E1 analogue.

An experimental model was used which includes intragastric instillation of 80 mM HCl and 0.6 ml bile/kg followed by intravenous infusion of live E coli in cats for up to three hours. This procedure regularly induces gastric mucosal ulcerations. Mucosal blood flow was measured by microspheres before, early, and late in sepsis. Total gastric blood flow was recorded electromagnetically. Mucosal regeneration capacity as reflected by the RNA/DNA ratio was measured. Misoprostol (a PGE1 analogue) was infused iv (5 micrograms/kg X h) or given locally in the stomach (10 micrograms/kg) before bacteriemia. Misoprostol did not influence the haemodynamic response to bacteria. The gastric mucosal damage was assessed either as an index representative for the entire corpus-fundus region or as the number of areas with intact surface epithelium within the series. Misoprostol iv protected the mucosa from ulceration compared with untreated septic controls while misoprostol intragastrically significantly reduced the number of damaged areas only. Topical misoprostol increased total gastric and mucosal blood flows early in sepsis compared to iv or no pretreatment while no difference was seen during late sepsis. The protective effect of misoprostol was thus not dependent on increased gastric mucosal blood flow. Nor was it mediated through effects on mucosal nucleic acid concentrations or ratio.

Animals↗
PubMed1985

Development of arteriovenous shunts in rejecting rat kidneys.

Arteriovenous shunts in rejecting rat kidneys were studied in vivo by injecting radiolabelled 15-micron microspheres into the graft artery 4-7 days after transplantation. Serum creatinine levels were measured and the transplants were examined microscopically. The radioactivity in the transplanted kidneys, lungs and the hind legs was recorded. A progressive increase in the amount of radioactivity found in the lungs started 5 days after allogenic transplantation but not after isotransplantation. Increased serum creatinine levels were first recorded on day 6 and focal necrosis or hemorrhages were not seen microscopically at any time. The results support the hypothesis that arteriovenous anastomoses are opened or created early as a part of the graft rejection process and not as a late consequence of tissue necrosis.

Animals↗
PubMed1985

Postnatal maturation of the islets of Langerhans in sheep. Light microscopic, immunohistochemical, morphometric, and ultrastructural investigations with particular reference to the transient appearance of argyrophil insulin immunoreactive cells.

The endocrine pancreas of lambs was found to offer an interesting animal model for some aspects of normal and pathological postnatal maturation of the islet parenchyma also in man. Normal features in lambs, previously observed in man, were the high volume density (5-8%) of the islet parenchyma, the high incidence of D (somatostatin) cells (about 30% even in young adult sheep), and the concentration of PP cells to the posterior part of the head of the pancreas. Particularly interesting was the presence in newborn lambs of large islet bodies (0.2-2 mm in diameter), consisting (to more than 90%) of large, argyrophil (Grimelius), granulated, parenchymal cells which were found to be insulin immunoreactive. Their secretion granules were smaller and more electron dense than those of the mature non-argyrophil B (insulin) cells. The argyrophil insulin immunoreactive cells often formed intercellular cavities and they could be equipped with microvilli and even cilia. At birth, these large islet bodies constituted more than half of the total islet parenchyma, but already during the first 10 days they underwent marked regressive changes (i.e. with large haemorrhages; "Blutinseln"); in 2-month-old lambs and in young adult sheep they had practically disappeared. These argyrophil insulin immunoreactive islet cells were considered to represent immature B cells with some persisting foetal characters. In 1- and 4-day-old lambs some non-argyrophil B cells in small islets of Langerhans harboured secretion granules of both types of B cells, indicating that a transformation could occur from 1 type to the other in this dual population of islet B cells. It was speculated that the argyrophil insulin immunoreactive cells could be homologues to the argyrophil islet cells often occurring in insulin-producing islet-cell neoplasms and in nesidiodysplasia in man.

Animals↗
PubMed1985

Role of free oxygen radicals in the development of gastrointestinal mucosal damage in Escherichia coli sepsis.

Live Escherichia coli were infused into anesthetized cats given 0.6 ml bile/kg and 80 mM HCl into the stomach. Systemic and pulmonary arterial blood pressures, cardiac output, and gastric blood flow were monitored. Gastrointestinal total wall and mucosal blood flow were measured by microspheres. The microscopic mucosal damage was graded 0-4 (stomach) or 0-5 (intestine). One group of cats (N = 8) received 5 mg yeast CuZn superoxide dismutase (SOD) as a bolus before bacteria followed by infusion 50 mg/3 hr. Four of these cats were also given catalase in the same dose. Controls (N = 8) had no treatment. After 3 hr gastric ulceration (grades 2-4) was found in controls but only in 50% of treated cats (P less than 0.1). About 50% and 25% of the cats in both groups developed significant small intestinal and colonic mucosal damage, respectively. SOD or SOD/catalase had no effect on late systemic hypotension, decrease in cardiac output, or transient increase in pulmonary pressure. Total gastric blood flow did not change, while at late sepsis gastric mucosal flow was decreased in the treated group. Small intestinal mucosal flow decreased in both series. It is concluded that free oxygen radicals may be of partial importance in the development of sepsis-induced gastric, but not intestinal, mucosal damage.

Animals↗
PubMed1984

The basic structural lesion of persistent neonatal hypoglycaemia with hyperinsulinism: deficiency of pancreatic D cells or hyperactivity of B cells?

Pancreatic tissue obtained at subtotal pancreatectomy from 15 infants with persistent hypoglycaemia with hyperinsulinism, and autopsy specimens from 23 age-matched normoglycaemic controls, were studied with morphometric methods after immunocytochemical staining of the four main islet cell types (A, B, D and pancreatic polypeptide cells). In three cases, a focal lesion was detected by gross examination. Macroscopic or microscopic examination did not distinguish the 12 other cases from controls. As found previously, nesidioblastosis was not a specific feature of the pancreas in infantile hypoglycaemia, being observed in age-matched controls as well. In cases with hypoglycaemia the volume density of B cells was not significantly increased; that of the A cells was within normal range. The volume density of pancreatic polypeptide cells was markedly augmented and that of somatostatin cells was significantly decreased. The mean nuclear volume of the B cells was increased by 40% in cases with diffuse changes, but in cases with a focal lesion this increase was restricted to the abnormal area. This finding is of decisive importance for diagnosis and has therapeutic implications. The increase in B-cell nuclear size is thought to reflect an enhanced functional activity of these cells. On the other hand, the figures obtained for the volume density of B and D cells must be viewed with some reservation because degranulation may interfere with accurate detection of these cells.

Cell Count↗
PubMed1984

Effects of dihydroergotamine on the feline cardiovascular response to intravenous infusion of live Escherichia coli bacteria.

A septic shock state was induced in cats by intravenous infusion of live Escherichia coli bacteria. Cats pretreated with an unspecific 5-HT blocker, dihydroergotamine (DHE), or with a specific 5-HT blocker, ketanserin, were compared with a series receiving bacteria without pretreatment. DHE pretreatment prevented the reduction in systemic arterial blood pressure found in the other series during the 2-hour period of septic shock. Pretreatment could not influence the increased vascular resistance in the pulmonary vascular bed or the early increase in pulmonary arterial blood pressure. Peripheral blood flow distribution was studied using radioactive labelled microspheres. Compared to bacteremia without pretreatment, the 5-HT blockers increased CNS blood flow and ketanserin also prevented the reduction in pancreatic blood flow. Gastric blood flow and gastric mucosal blood flow remained unchanged in all series as did the small intestinal total blood flow. Small intestinal mucosal blood flow, however, was reduced after 2 h of bacteremia. Microscopy revealed no gastric epithelial damage while the jejunal mucosa was characteristically damaged. There was no correlation between the changes in the small intestinal blood flow and the degree of mucosal damage, however, supporting the countercurrent theory for the pathogenesis of these lesions.

Animals↗
PubMed1984

Acute gastric mucosal ulceration in septic shock. An experimental study on pathogenic mechanisms.

Intravenous infusion of live. E. coli bacteria in cats did not induce microscopic damage to the gastric mucosa within 3 hours. However, if the cats before the induction of bacteremia were given 80 mM HCl and 0.6 ml gallbladder bile/kg b.w. microscopic mucosal damage developed regularly in the corpus-fundus area of the stomach. The gastric mucosal damage was not associated with significant decrease of total gastric blood flow as measured continuously electromagnetically or decreased gastric mucosal blood flow measured early and late during sepsis using radioactively labelled microspheres. Neither was the development of gastric mucosal damage associated with reduced gastric wall collagen concentration nor in RNA, DNA concentrations or RNA/DNA ratio in the gastric mucosa.

Acute Disease↗
PubMed1984

Absence of cytotoxicity of islet cell surface antibodies in vivo despite complement-mediated cytotoxic effects to islet cells in vitro.

Islet cell surface antibodies (ICSA) have been generated to investigate relations between recognition of specific antigens and cytotoxic reactions on pancreatic islet cells. Sera from rabbits which had been directly immunized with islet cells or intact rat islets exhibited positive immunofluorescence with both rat and rabbit pancreatic islet cells. Analysis by SDS polyacrylamide gel electrophoresis and autoradiography of islet cells proteins prelabeled with [35S]methionine revealed that these sera precipitated a specific protein of Mr 40000. Serum from immunized rabbits stimulated 51Cr-release in suspensions of dispersed islet cells prepared from neonatal rats. Absorption to lymphocytes and liver powder removed antibodies that were cytotoxic to lymphocytes but complement-mediated cytotoxicity against islet cells persisted. Circulating ICSA neither in rabbits nor in rats caused changes in blood glucose. Moreover, no major alterations of islet cells in the immunized rabbits were observed upon electron microscopic examination. It is concluded that ICSA are capable of recognizing specific islet cell antigens and thus mediate complement-dependent cytotoxic reactions in vitro, but the mere presence of ICSA is obviously not sufficient to induce diabetes in vivo under the conditions used.

Animals↗
PubMedDate not supplied

Fatal thrombo-embolic complications at aorto-femoral angiography.

Fatal complications due to angiographic procedures are rare. An awareness of these complications is, however, mandatory in order to be able to prevent them. This report concerns three fatal cases with a deleterious complication of distal macro- and microembolization in connection with the angiographic procedure. In all cases the local circulation was surgically restored. The microcirculation was 'out of reach' and all three patients succumbed with profound tissue ischemia.

Aged↗
PubMedDate not supplied

Peroperative arterial recanalization with Kensey dynamic angioplasty. Histopathologic studies.

The morphology of occluded superficial femoral artery segments and of particles in the effluent fluid after dynamic Kensey catheter angioplasty was analyzed in six patients treated with an intraoperative retrograde technique. The effluent was collected during the procedure and the arteries were extirpated for microscopy after the recanalization attempt. In three patients with easy recanalization, histologic study showed highly cellular, proliferating connective tissue. In three patients with unsuccessful recanalization, mature, cell-poor connective healing tissue obliterated the lumen. The effluent contained particles measuring 14 to 320 microns, the largest of which had the potential to occlude small arteries. The results of this pilot study are to be regarded as preliminary.

Aged↗